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Study Objectives Phase II trial to study the effectiveness of broxuridine in treating patients who are undergoing surgery for stage I or stage II prostate cancer. Broxuridine may help doctors determine the rate of growth of prostate tumors and help them plan effective treatment Conditions: Stage I Prostate Cancer, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer Intervention / Treatment: DRUG: bromodeoxyuridine, PROCEDURE: conventional surgery, OTHER: laboratory biomarker analysis Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Diagnosis of stage I or II (T1 <= age <= 2) carcinoma of the prostate * PSA greater than 8 ng/mL * Abnormal findings on digital rectal examination * Eligible for radical prostatectomy * Performance status - ECOG 0 or 1 * No prior biologic therapy * No prior chemotherapy * No prior neoadjuvant hormonal therapy * No prior radiotherapy * See Disease Characteristics * No prior therapy that would affect tumor growth rates or volume

NCT_ID NCT00003832

Study_NameBroxuridine Plus Surgery in Treating Patients With Stage I or Stage II Prostate Cancer

Study Objectives The primary goal is to determine the maximum tolerated dose (MTD) of the combination of T-DM1 and non-pegylated liposomal doxorubicin in metastatic breast cancer (mBC) patients previously treated with taxanes and trastuzumab-based therapy. In addition, pharmacokinetic data on the combination of T-DM1 and liposomal doxorubicin will be obtained. Conditions: Breast Cancer Intervention / Treatment: DRUG: Trastuzumab and non-pegylated liposomal doxorubicin Location: France, Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: * Signed informed consent * Patient able and willing to comply with protocol * Cytologically or histologically confirmed carcinoma of the breast. * Incurable locally advanced or metastatic disease who have previously received up to two previous chemotherapy regimens in this setting. Patient must have progressed or relapsed on or after taxane and trastuzumab-based therapy. * HER2-positive disease * At least one measurable lesion according to RECIST version 1.1; or patients with non measurable lesions could be included with these exceptions: o patients with only blastic bone lesions / with only pleural, peritoneal or cardiac effusion, or meningeal carcinomatosis * >= 18 years * Eastern Cooperative Oncology Group (ECOG) 0 or 1 * Life expectancy >= 3 months * Adequate bone marrow function: * Hemoglobin >= 10 g/dl. * Absolute neutrophil count >= 1.5 x 109/L. * Platelets >= 100 x 109/L without transfusions within 21 days * International normalized ratio (INR) < 1.5 × the upper limit of normal (ULN). * Adequate hepatic and renal function * Adequate cardiovascular function with LVEF >= 55% * Recovery from all reported toxicities of previous anti-cancer therapies to baseline or grade <= 1 (CTCAE version 4.0), except for alopecia * For women of childbearing potential and not postmenopausal, and who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy, and men with partners of childbearing potential, use of forms of contraception Exclusion Criteria: * Previous treatment with T-DM1 or anthracyclines * More than two chemotherapeutic regimens for locally advanced incurable disease or metastatic disease * Prior anti-cancer treatment with chemotherapy, immunotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin-C), hormonal therapy or lapatinib within 7 days, prior trastuzumab within 21 days (7 days if weekly trastuzumab) or any other targeted therapy within the last 21 days prior to starting study treatment * Previous radiotherapy for the treatment of unresectable, locally advanced/recurrent or mBC is not allowed if: * The last fraction of radiotherapy has been administered within 21 days prior to first study drug administration (except for brain irradiation; at least 28 days will be required) * More than 25% of marrow-bearing bone has been irradiated * History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to the active substance or to any of the excipients of T-DM1 or non-pegylated liposomal doxorubicin * Patients with central nervous system (CNS) involvement. However, patients with metastatic CNS tumors may participate in this trial if the patient is > 4 weeks from radiotherapy completion, is clinically stable with respect to CNS tumor at the time of study entry and is not receiving steroid therapy for brain metastases * Severe/uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements. * Cardiopulmonary dysfunction * Current peripheral neuropathy of Grade >= 3 per the NCI CTCAE, v4.0 * History of a decrease in LVEF to < 40% or symptomatic congestive heart failure (CHF) with previous trastuzumab treatment * Prior malignancy, other than carcinoma in situ of the cervix, or non-melanoma skin cancer, unless the prior malignancy was cured >= 5 years before first dose of study drug with no subsequent evidence of recurrence * Current known active infection with HIV, hepatitis B, and/or hepatitis C virus * Women who are pregnant or breast-feeding

NCT_ID NCT02562378

Study_NameT-DM1 and Non-pegylated Liposomal Doxorubicin in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer

Study Objectives Treatment of patients with locally advanced rectal cancer (LARC) is multidisciplinary and consists of neoadjuvant chemoradiotherapy (nCRT) followed by surgical removal of the rectal tumor and potentially tumor positive lymph nodes. 1. After surgery, in 15 to 27% of patients that received nCRT no tumor cells can be detected during histopathological examination. In today's clinical practice, all of these patients with a pathological complete response (pCR) are operated upon, with substantial morbidity and mortality. The 5-year survival is 83.3% for patients with a pCR, and 65.6% for those without pCR. Response after nCRT is currently evaluated using magnetic resonance imaging (MRI). However, as MRI cannot differentiate between molecular characteristics of tissue, prediction of treatment response can be inaccurate. In patients with a potential cCR on MRI, additionally a high-definition white-light (HD-WL) endoscopy is performed with biopsies of the previous tumor location. If both MRI and HD-WL endoscopy confirm a potential cCR, patients can also be treated with a watch-and-wait approach, including frequent follow-up with HD-WL endoscopy and MRI. This potentially prevents extensive surgical procedures for patients in which this is not required. However, MRI and HD-WL endoscopy often remain insufficient for identification of cCR. Therefore, novel imaging methods are needed for accurate prediction of treatment response in order to select patients. The investigators believe fluorescence molecular endoscopy (FME) could be a promising technique for evaluation of treatment response. 2. During surgery, tumor-negative resection margins are of great prognostic value. Currently, surgeons rely on visual and tactile inspection for differentiation between malignant and healthy tissue. When in doubt, a frozen section can be obtained, which is time consuming and poses a high risk of sampling error. However, 14.7% of patients still have tumor-positive resection margins, increasing the risk of local recurrence and worsening outcome. Therefore, there is a need for novel imaging techniques that can be used intraoperatively to improve margin assessment. The investigators believe molecular fluorescence-guided surgery (MFGS) could be a promising technique for evaluation of resection margins. Conditions: Rectal Cancer Intervention / Treatment: DRUG: Cetuximab-IRDye800, DEVICE: Fluorescent molecular endoscopy and surgery Location: Netherlands Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: DIAGNOSTIC Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Locally advanced rectal cancer, in multi-disciplinary colorectal oncology meeting agreed on long course neoadjuvant chemoradiotherapy, followed by surgical removal of the primary tumor; * Clinical suspicion of residual tumor after neoadjuvant chemoradiotherapy; * Age >= 18 years; * Written informed consent. Exclusion Criteria: * Medical or psychiatric conditions that compromise the patient's ability to give informed consent; * Concurrent uncontrolled medical conditions; * Pregnancy or breast feeding. A negative pregnancy test must be available for women of childbearing potential (i.e. premenopausal women with intact reproductive organs and women less than two years after menopause); * Received an investigational drug within 30 days prior to the dose of cetuximab- IRDye800CW; * History of infusion reactions to cetuximab or other monoclonal antibodies; * Had within 6 months prior to enrollment: myocardial infarction, cerebrovascular accident, uncontrolled cardiac heart failure, significant liver disease, unstable angina pectoris; * Patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents; * Evidence of QT prolongation on an ECG made within three months prior to inclusion (greater than 440 ms in males or greater than 450 ms in females); * Magnesium, potassium and calcium deviations that might lead to cardiac rhythm (grade II or higher deviations by CTCAE), determined within three months prior to inclusion.

NCT_ID NCT04638036

Study_NameFluorescence Molecular Endoscopy and Molecular Fluorescence-guided Surgery in Locally Advanced Rectal Cancer

Study Objectives Multiple myeloma is a malignant incurable hematological disease where survival has been significantly improved by high-dose melphalan with autologous stem cell support (ASCT) in younger patients. However, the disease will eventually relapse and new treatment is demanded. Bortezomib is a newly approved drug for treating relapsing multiple myeloma. It has a different biological effect and response even in patients refractory to conventional chemotherapy. The purpose of the study is in a randomized design to investigate if addition of bortezomib by 20 injections during a 4 months period starting 3 month after ASCT can prolong the time to progression compared to patients receiving no consolidation or maintenance therapy. Conditions: Multiple Myeloma Intervention / Treatment: DRUG: bortezomib Location: Sweden, Iceland, Denmark, Norway, Finland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Symptomatic myeloma diagnosis according to criteria in attachment 3 * ASCT is performed or has been performed in the last five weeks (time limit two weeks for patients randomised at 2nd transplantation) as a part of primary therapy * Signed informed consent given prior to any study related activities have been performed Exclusion Criteria: * Prior exposure to bortezomib * Allogeneic transplantation scheduled as a part of the primary treatment * Neuropathy > Grade 2 (neurological symptoms interfering with ADL) * Non-secreting myeloma * Other concurrent disease making bortezomib treatment unsuitable * Positive pregnancy test (only applicable for women with childbearing potential) * Has known or suspected hypersensitivity or intolerance to boron, mannitol, or heparin, if an indwelling catheter is used * Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 6, NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis * History of hypotension or has decreased blood pressure (sitting systolic blood pressure [SBP] £100 mmHg and/or sitting diastolic blood pressure [DBP] £60 mmHg) * Serious medical or psychiatric illness likely to interfere with participation in this clinical study * Have received an experimental drug or used an experimental medical device within 4 weeks prior to inclusion into the study

NCT_ID NCT00417911

Study_NameEfficacy of Bortezomib Consolidation After High-dose Melphalan With Stem Cell Support in Myeloma Patients

Study Objectives This phase II trial studies the side effects of giving bortezomib together with vorinostat and to see how well it works in treating patients with multiple myeloma who have undergone autologous stem cell transplant. Bortezomib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving bortezomib together with vorinostat after an autologous stem cell transplant may stop the growth of any cancer cells that remain after transplant. Conditions: DS Stage I Plasma Cell Myeloma, DS Stage II Plasma Cell Myeloma, DS Stage III Plasma Cell Myeloma Intervention / Treatment: DRUG: Bortezomib, DRUG: Vorinostat Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Any autologous patient who underwent high dose melphalan (>= 140 mg/m^2) therapy or peripheral blood stem cell (PBSC) rescue for any stage of multiple myeloma and did not participate in another clinical transplant trial whose primary endpoint is also evaluating long-term, disease-free survival, or survival * Platelet count (transfusion independent) > 75,000 cells/mm^3 and absolute granulocyte count > 1500 cells/mm^3 for 5 calendar days after recovery from high dose therapy * Consenting for study between 30 days to 120 days after transplant * Female patient of childbearing potential has a negative serum pregnancy test beta-hCG within 72 hours prior to receiving the first dose of vorinostat * Female patient is either post-menopausal, free from menses for >= 2 years, surgically sterilized, or willing to use 2 adequate barrier methods of contraception to prevent pregnancy or agrees to abstain from heterosexual activity throughout the treatment on study, starting with visit 1 and for 3 months afterward * Male patient agrees to use an adequate method of contraception for the duration of the treatment on study and for 3 months afterward Exclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) performance status >= 2 * A left ventricular ejection fraction less than 45% pre-transplant * Congestive heart disease with transplant, history of myocardial infarction (MI), history of coronary artery disease, or prolonged corrected QT interval (QTC) * Total bilirubin greater than 2 mg/ml (unless history of Gilbert's disease) * Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) > 2.5 x upper limit of normal (ULN) * Creatinine clearance < 20 ml/minute, calculated by Cockroft-Gault formula or measured urine * Cannot give informed consent * Untreated systemic infection * Poorly-controlled diabetes mellitus (DM) * >= grade 3 peripheral neuropathy * Prior history of human immunodeficiency virus (HIV) positivity with pre-transplant evaluation or known history of hepatitis B or C * Previous history of hypersensitivity to Bortezomib, boron, or mannitol; known hypersensitivity to the components of study drug or its analogs * Require therapeutic anticoagulation treatment, especially with coumadin * Potassium (K) and magnesium (Mg) < normal limits * Patient who has had chemotherapy, radiotherapy, or biological therapy, within 30 days (42 days for nitrosoureas or mitomycin C) prior to initial dosing with study drug(s) or who has not recovered from adverse events due to agents administered more than 30 days earlier; patients who have received localized consolidation radiation to bone only less than 30 days prior to study entry are allowed * Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drugs * Patient had prior treatment with an histone deacetylase inhibitor (HDAC) inhibitor (e.g., romidespin [depsipeptide], NSC-630176, MS 275, LAQ-824, belinostat [PXD-101], LBH589, MGCD0103, CRA024781, etc.) * Patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study * Patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period * History of central nervous system (CNS) disease * Symptomatic ascites or pleural effusions * Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial * Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs, substance abuse or had a recent history (within the last year) of drug or alcohol abuse * Patient is pregnant or breast-feeding, or expecting to conceive or father children within the projected duration of the study * Patient with a history of a prior malignancy with the exception of cervical intraepithelial neoplasia; non-melanoma skin cancer; adequately treated localized prostate carcinoma with prostate-specific antigen (PSA) < 1.0; or who has undergone potentially curative therapy with no evidence of disease for five years, and/or who is deemed at low risk for recurrence by his/her treating physician * Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or is not in the best interest of the patient to participate * Patient has a history of a gastrointestinal surgery or other procedures that might, in the opinion of the investigator, interfere with the absorption or swallowing of the study drugs

NCT_ID NCT00839956

Study_NameBortezomib and Vorinostat in Treating Patients With Multiple Myeloma Who Have Undergone Autologous Stem Cell Transplant

Study Objectives This phase I/II trial studies the side effects of sitravatinib and how well it works with nivolumab in treating patients with kidney cancer that has spread to other places in the body. Sitravatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving sitravatinib and nivolumab may work better in treating patients with kidney cancer. Conditions: Clear Cell Renal Cell Carcinoma, Metastatic Kidney Carcinoma, Stage III Renal Cell Cancer AJCC v7, Stage IV Renal Cell Cancer AJCC v7 Intervention / Treatment: OTHER: Laboratory Biomarker Analysis, BIOLOGICAL: Nivolumab, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, DRUG: Sitravatinib Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with histologically or cytologically confirmed metastatic/advanced clear cell RCC, or RCC with a clear cell component, who have received 1 or 2 prior anti-angiogenic therapy regimens (+/- cytokine therapy with interleukin-2 or interferon-alfa) in the advanced or metastatic setting; examples of anti-angiogenic agents include, but are not limited to, sorafenib, sunitinib, pazopanib, axitinib, and bevacizumab * There must be evidence of progression on or after last treatment regimen received and within 6 months of enrollment * Patients must have at least one measurable site of disease, defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and measures >= 15 mm with conventional techniques or >= 10 mm with more sensitive techniques such as magnetic resonance imaging (MRI) or spiral computed tomography (CT) scan; if the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation * Karnofsky performance status >= 70 * Hemoglobin >= 9 g/dl (treatment allowed) (within 14 days prior to study entry) * Absolute neutrophil count >= 1,500/uL (within 14 days prior to study entry) * Platelets >= 100,000/uL (within 14 days prior to study entry) * Total bilirubin =< 1.5 mg/dl (within 14 days prior to study entry) * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (ULN), except in known hepatic metastasis, wherein may be < 5 x ULN (within 14 days prior to study entry) * Serum creatinine =< 1.5 x ULN (as long as patient does not require dialysis); a) may receive transfusion b) if creatinine is not < 1.5 x ULN, then calculate by Cockcroft-Gault methods or local institutional standard and creatinine clearance (CrCl) must be >= 40 mL/kg/1.73 m^2 (within 14 days prior to study entry) * International normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.5 x ULN within 14 days prior to study entry; therapeutic anticoagulation with warfarin is allowed if target INR =< 3 on a stable dose of warfarin or on a stable dose of low molecular weight (LMW) heparin for > 2 weeks (14 days) at the time of enrollment * Female patients of childbearing potential (not postmenopausal for at least 12 months and not surgically sterile) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 14 days before study entry; pregnancy test must be repeated if performed > 14 days before starting study drug * Women must not be breastfeeding * Patients with a history of major psychiatric illness must be judged (by the treating physician) able to fully understand the investigational nature of the study and the risks associated with the therapy * Patients with controlled brain metastases are allowed on protocol if they had solitary brain metastases that was surgically resected or treated with radiosurgery or gamma knife, without recurrence or edema for 1 month (4 weeks) Exclusion Criteria: * Patients must not have any other malignancies within the past 2 years except for in situ carcinoma of any site, or adequately treated (without recurrence post-resection or post-radiotherapy) carcinoma of the cervix or basal or squamous cell carcinomas of the skin or active non-threatening second malignancy that would not, in the investigator's opinion, potentially interfere with the patient's ability to participate and/or complete this trial; examples include but not limited to: urothelial cancer grade Ta or T1, adenocarcinoma of the prostate treated by active surveillance * Patients currently receiving anticancer therapies or who have received anticancer therapies within 2 weeks (14 days) from enrollment into this study (including chemotherapy and targeted therapy) are excluded; also, patients who have completed palliative radiation therapy more than 14 days prior to the first dose of MGCD516 are eligible * Patients, who have had a major surgery or significant traumatic injury (injury requiring > 4 weeks [28 days] to heal) within 4 weeks (28 days) of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that are expected to require major surgery during the course of the study * Patients who have been previously treated with mTOR inhibitors such as everolimus and temsirolimus, or with c-MET inhibitors such as cabozantinib * Patients who have organ allografts * Known or suspected autoimmune disease; patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus or autoimmune vasculitis (e.g., Wegener's granulomatosis) are excluded from this study; patients with a history of Hashimoto's thyroiditis only requiring hormone replacement, type I diabetes, or psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are allowed to participate * Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) * Any underlying medical condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea, uncontrolled nausea, vomiting, malabsorption syndrome or small bowel resection that may significantly alter the absorption of MGCD516 * Patients must not have received prior anticancer therapy with any immune checkpoint inhibitors such as anti-CLTA-4, anti-PD1, or anti-PD-L1 * Patients receiving any concomitant systemic therapy for renal cell cancer are excluded * Patients must not be scheduled to receive another experimental drug while on this study * Patients who are on high dose steroid (e.g., > 10 mg prednisone daily or equivalent) or other more potent immune suppression medications (e.g., infliximab); topical, inhaled, intra-articular, ocular, or intranasal corticosteroids (with minimal systemic absorption) are allowed; a brief course (=< 48 hours) of systemic corticosteroids for prophylaxis (e.g., from contrast dye allergy) is permitted * Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: symptomatic congestive heart failure of New York Heart Association class III or IV; unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease; severely impaired lung function as defined as oxygen (O2) saturation that is 88% or less at rest on room air; uncontrolled diabetes as defined by blood glucose > 200 mg/dl (11.1 mmol/l); systemic fungal, bacterial, viral, or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement) despite appropriate antibiotics or other treatment; liver disease such as cirrhosis or chronic active hepatitis; positive test for hepatitis B virus (HBV) using HBV surface antigen (HBV sAg) test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection * Patients must not have history of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of MGCD516 or nivolumab or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications * Patients should not receive immunization with attenuated live vaccines within one week (7 days) of study entry or during study period * Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases * Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods; if barrier contraceptives are being used, these must be continued throughout the trial by both sexes; hormonal contraceptives are not acceptable as a sole method of contraception; (women of childbearing potential must have a negative urine or serum pregnancy test within 14 days prior to study entry; pregnancy test must be repeated if performed > 14 days before administration of MGCD516) * Any patients who cannot be compliant with the appointments required in this protocol must not be enrolled in this study * Concurrent therapy with medications known to significantly prolong the QT interval and/or associated with increased risk for Torsade de Pointes arrhythmia; the principal investigator (PI) is the final arbiter in questions related to eligibility * Patients with left ventricular ejection fraction (LVEF) < 40%

NCT_ID NCT03015740

Study_NameSitravatinib and Nivolumab in Treating Patients With Advanced or Metastatic Kidney Cancer

Study Objectives This randomized pilot clinical trial studies whether acetylcysteine oral rinse will lessen saliva thickness and painful mouth sores in patients with head and neck cancer undergoing radiation therapy. Side effects from radiation therapy to the head and neck, such as thickened saliva and mouth sores, may interfere with activities of daily living such as eating and drinking, and may also cause treatment to be stopped or delayed. Acetylcysteine rinse may reduce saliva thickness and mouth sores, and improve quality of life in patients with head and neck cancer undergoing radiation therapy. Conditions: Mucositis, Oral Complications, Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Basal Cell Carcinoma of the Lip, Recurrent Lymphoepithelioma of the Nasopharynx, Recurrent Lymphoepithelioma of the Oropharynx, Recurrent Mucoepidermoid Carcinoma of the Oral Cavity, Recurrent Salivary Gland Cancer, Recurrent Squamous Cell Carcinoma of the Larynx, Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity, Recurrent Squamous Cell Carcinoma of the Nasopharynx, Recurrent Squamous Cell Carcinoma of the Oropharynx, Recurrent Verrucous Carcinoma of the Larynx, Recurrent Verrucous Carcinoma of the Oral Cavity, Stage I Adenoid Cystic Carcinoma of the Oral Cavity, Stage I Basal Cell Carcinoma of the Lip, Stage I Lymphoepithelioma of the Nasopharynx, Stage I Lymphoepithelioma of the Oropharynx, Stage I Mucoepidermoid Carcinoma of the Oral Cavity, Stage I Salivary Gland Cancer, Stage I Squamous Cell Carcinoma of the Larynx, Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage I Squamous Cell Carcinoma of the Nasopharynx, Stage I Squamous Cell Carcinoma of the Oropharynx, Stage I Verrucous Carcinoma of the Larynx, Stage I Verrucous Carcinoma of the Oral Cavity, Stage II Adenoid Cystic Carcinoma of the Oral Cavity, Stage II Basal Cell Carcinoma of the Lip, Stage II Lymphoepithelioma of the Nasopharynx, Stage II Lymphoepithelioma of the Oropharynx, Stage II Mucoepidermoid Carcinoma of the Oral Cavity, Stage II Salivary Gland Cancer, Stage II Squamous Cell Carcinoma of the Larynx, Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage II Squamous Cell Carcinoma of the Nasopharynx, Stage II Squamous Cell Carcinoma of the Oropharynx, Stage II Verrucous Carcinoma of the Larynx, Stage II Verrucous Carcinoma of the Oral Cavity, Stage III Adenoid Cystic Carcinoma of the Oral Cavity, Stage III Basal Cell Carcinoma of the Lip, Stage III Lymphoepithelioma of the Nasopharynx, Stage III Lymphoepithelioma of the Oropharynx, Stage III Mucoepidermoid Carcinoma of the Oral Cavity, Stage III Salivary Gland Cancer, Stage III Squamous Cell Carcinoma of the Larynx, Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage III Squamous Cell Carcinoma of the Nasopharynx, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage III Verrucous Carcinoma of the Larynx, Stage III Verrucous Carcinoma of the Oral Cavity, Stage IV Lymphoepithelioma of the Nasopharynx, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity, Stage IVA Basal Cell Carcinoma of the Lip, Stage IVA Lymphoepithelioma of the Oropharynx, Stage IVA Mucoepidermoid Carcinoma of the Oral Cavity, Stage IVA Salivary Gland Cancer, Stage IVA Squamous Cell Carcinoma of the Larynx, Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVA Squamous Cell Carcinoma of the Oropharynx, Stage IVA Verrucous Carcinoma of the Larynx, Stage IVA Verrucous Carcinoma of the Oral Cavity, Stage IVB Adenoid Cystic Carcinoma of the Oral Cavity, Stage IVB Basal Cell Carcinoma of the Lip, Stage IVB Lymphoepithelioma of the Oropharynx, Stage IVB Mucoepidermoid Carcinoma of the Oral Cavity, Stage IVB Salivary Gland Cancer, Stage IVB Squamous Cell Carcinoma of the Larynx, Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVB Squamous Cell Carcinoma of the Oropharynx, Stage IVB Verrucous Carcinoma of the Larynx, Stage IVB Verrucous Carcinoma of the Oral Cavity, Stage IVC Adenoid Cystic Carcinoma of the Oral Cavity, Stage IVC Basal Cell Carcinoma of the Lip, Stage IVC Lymphoepithelioma of the Oropharynx, Stage IVC Mucoepidermoid Carcinoma of the Oral Cavity, Stage IVC Salivary Gland Cancer, Stage IVC Squamous Cell Carcinoma of the Larynx, Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVC Squamous Cell Carcinoma of the Oropharynx, Stage IVC Verrucous Carcinoma of the Larynx, Stage IVC Verrucous Carcinoma of the Oral Cavity, Tongue Cancer Intervention / Treatment: DRUG: acetylcysteine, OTHER: placebo, OTHER: quality-of-life assessment, OTHER: questionnaire administration Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Histological confirmation of tumor of the oral cavity, oropharynx, supraglottic larynx, or nasopharynx * Receiving concurrent chemoradiotherapy/chemobiotherapy to a minimum dose equivalent to 60 Gy in 30 fractions in the adjuvant or definitive setting * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2 * Initiation of investigational agent =< 3 days after initiation of radiotherapy * Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only * Ability to complete questionnaire(s) by themselves or with assistance * Provide informed written consent * Willing to return mail-in questionnaires during the observation phase of the study Exclusion Criteria: * Any of the following: * Pregnant women * Nursing women * Men or women of childbearing potential who are unwilling to employ adequate contraception * Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens * Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm * History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias * Receipt of induction chemotherapy * Previous receipt of head and neck irradiation * Utilization of amifostine during radiotherapy * Greater than or equal to grade 2 dry mouth prior to chemoradiotherapy or greater than or equal to grade 2 mucositis * Previous intolerance/adverse effect/allergy to any component of the placebo or active agent * History of Sjogren's, lupus or scleroderma

NCT_ID NCT02123511

Study_NameAcetylcysteine Rinse in Reducing Saliva Thickness and Mucositis in Patients With Head and Neck Cancer Undergoing Radiation Therapy

Study Objectives This is a randomized, open-label, multicenter, Phase 3 study comparing the efficacy and safety of eribulin with dacarbazine in subjects with advanced soft tissue sarcoma who have disease progression within 6 months prior to study enrolment following standard therapies which must have included an anthracycline, unless contraindicated and then at least one additional regimen after failure of the anthracycline. Conditions: Soft Tissue Sarcoma Intervention / Treatment: DRUG: Eribulin mesylate 1.4 mg/m^2 intravenous, DRUG: Dacarbazine of 850 mg/m^2, or 1,000 mg/m^2, or 1,200 mg/m^2 IV Location: Poland, Thailand, United Kingdom, Australia, Austria, Denmark, France, Korea, Republic of, Singapore, Netherlands, Canada, New Zealand, Germany, Spain, Czechia, Italy, Romania, Argentina, Israel, United States, Brazil, Belgium, Russian Federation Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically confirmed diagnosis of soft tissue sarcoma of high or intermediate grade with one of the following histological subtypes: * Adipocytic sarcoma, including: * Dedifferentiated * Myxoid * Round Cell * Pleomorphic - Leiomyosarcoma * Documented evidence of advanced (locally recurrent, locally advanced and/or metastatic) adipocytic (restricted to subtypes listed in Inclusion 1) or leiomyosarcoma, incurable by surgery and/or radiotherapy. * Subjects should have received at least two standard systematic regimens for advanced soft tissue sarcoma one of which must have included an anthracycline (unless contraindicated). * Radiographic evidence of disease progression by RECIST criteria on or after the last anti-cancer therapy within the 6 months prior to randomization. * Presence of measurable disease meeting the following criteria: * At least one lesion of greater than or equal to 1.0 cm in long-axis diameter for non lymph nodes or greater than or equal to 1.5 cm in short-axis diameter for lymph nodes which is serially measurable according to RECIST 1.1 using either computerized tomography or magnetic resonance imaging or panoramic and close-up color photography. * Lesions that have had radiotherapy must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion. * Eastern Cooperative Oncology Group, performance status of 0, 1 or 2. * Adequate renal function defined as calculated creatinine clearance greater than 50 mL/min per the Cockroft and Gault formula. * Adequate bone marrow function, defined as: * Absolute neutrophil count (ANC) greater than or equal to 1,500/mm3 or greater than or equal to 1.5 x 10^9/L. * Platelet count greater than or equal to 100,000/mm3 or greater than or equal to 100 x 10^9/L. * Hemoglobin (Hb) greater than or equal to 10g/dL at baseline (blood transfusions,hematopoietic growth factors and hematinics are allowed during the Prerandomization Phase to correct Hb values less than 10g/dL). * Adequate liver function, defined as: * Bilirubin less than or equal to 1.5 times the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert's syndrome. * Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 times ULN. For total ALP greater than 3 times ULN, the ALP liver isoenzyme must be less than or equal to 3 times ULN. * All female subjects will be considered to be of child-bearing potential unless they are postmenopausal (at least 12 months consecutive amenorrhea, in the appropriate age group and without other known or suspected cause), or have been sterilized surgically (i.e., bilateral tubal ligation greater than or equal to 1 menstrual cycle prior to randomization, or have undergone a hysterectomy and/or bilateral oophorectomy). Female subjects of child-bearing potential must agree to use two forms of highly effective contraception from the last menstrual period prior to randomization (or use a double barrier method as described below until they are on two forms of highly effective contraception for at least one menstrual cycle), during the study treatment, and for 3 months after the final dose of study treatment. Female subjects exempt from this requirement are subjects who practice total abstinence. If currently abstinent, the subject must agree to use a double barrier method of contraception, i.e., condom and occlusive cap (diaphragm or cervical/vault caps) with spermicide or until they are on two forms of highly effective contraception for at least one menstrual cycle if they become sexually active during the study treatment and for 3 months after the final dose of study treatment. Highly effective contraception includes: * Placement of intrauterine device or system, * Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault cap) with spermicide, * Established hormonal contraceptive methods: oral, injectable or implant. Female subjects who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product from the last menstrual period prior to randomization, and must continue to use the same hormonal contraceptive product during study treatment, and for 3 months after the first dose of study treatment. * Vasectomized partner with confirmed azoospermia. * Male subjects and their female partner who are of child-bearing potential (as defined in Inclusion 10), and are not practicing total abstinence, must agree to use two forms of highly effective contraception from the last menstrual period of their female partner prior to randomization (or use a double barrier method as described above until they are on two forms of highly effective contraception for at least one menstrual cycle), during study treatment, and for 3 months (or 6 months if they received dacarbazine) after the final dose of study treatment. If currently abstinent, must agree to use a double barrier method of contraception if they become sexually active, or until they are on two forms of highly effective contraception as described above. * Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol. * Males or females aged greater than or equal to 18 years at the time of informed consent. Exclusion Criteria: * Subjects who have received any anti-cancer therapy, including radiotherapy, cytotoxic, hormonal, biological (including humanized antibodies) and targeted agents within 21 days, or five half-lives of the drug (whichever is longer) prior to randomization. * Subjects who have not recovered from acute toxicities as a result of prior anti-cancer therapy to less than or equal to Grade 1, according to Common Terminology Criteria for Adverse Events (CTCAE), except for peripheral neuropathy (see Exclusion 6) and alopecia. * Subjects that have previously been treated with dacarbazine or its analogue temozolomide or eribulin. * Major surgery within 21 days prior to randomization. * Pre-existing peripheral neuropathy greater than CTCAE Grade 2. * Significant cardiovascular impairment, defined as: * Cardiac failure, New York Heart Association (NYHA) Class II according to the NYHA Functional Classification, * Unstable angina or myocardial infarction within 6 months of enrolment, * Serious and potentially life-threatening arrhythmia. * Subjects with a high probability of Long QT Syndrome or QTc interval prolongation of more than or equal to 501 msec on at least two separate ECGs, following correction of any electrolyte imbalance. * Subjects with known central nervous system metastases. * Any serious concomitant illness or infectious disease requiring treatment, or infectious disease not requiring treatment, but with significant risks for myelosuppressive complications associated with chemotherapy. * Any malignancy that required treatment, or has shown evidence of recurrence (except for soft tissue sarcoma, non-melanoma skin cancer, or histologically confirmed complete excision of carcinoma in situ) during the 5 years prior to randomization. * Female subjects must not be pregnant as documented by a negative beta-human chorionic gonadotropin (beta-hCG) test with a minimum sensitivity 25 IU/L or equivalent unit of beta-hCG at Screening and Baseline, or breastfeeding. * Hypersensitivity to the active substance, or any of the excipients of the eribulin drug product, or dacarbazine, (please refer to the dacarbazine prescribing information). * Any medical or other condition which, in the opinion of the PI or designee, will preclude participation in a clinical trial.

NCT_ID NCT01327885

Study_NamePhase 3 Study to Compare the Efficacy and Safety of Eribulin With Dacarbazine in Subjects With Soft Tissue Sarcoma

Study Objectives This partially randomized phase I/IIb trial studies the side effects and best dose of IDO1 inhibitor INCB024360 in combination with DEC-205/NY-ESO-1 fusion protein CDX-1401 and poly ICLC and to see how well they work in treating patients with ovarian, fallopian tube, or primary peritoneal cancer who no longer have evidence of disease. Antigens (such as cancer/testis antigen \[NY-ESO-1\] protein) are found on many cancer cells. Vaccines made from NY-ESO-1 protein may cause the immune system to produce immune cells and antibodies that may help locate the NY-ESO-1 and/or cancer/testis antigen 2 (LAGE-1) antigens on cancer cells. By finding them, the immune system may then work to control or eliminate the remaining cancer cells. INCB024360 is an inhibitor of an enzyme called indoleamine 2,3 dioxygenase (IDO). This enzyme is produced by tumor cells to disable immune cells, and limit the efficacy of immune attack. Giving DEC-205/NY-ESO-1 fusion protein CDX-1401 with poly ICLC and IDO1 inhibitor INCB024360 may generate stronger and more long lasting anti-cancer immune responses in patients with ovarian, fallopian tube, and primary peritoneal cancer in remission. Conditions: Fallopian Tube Carcinoma, Ovarian Carcinoma, Primary Peritoneal Carcinoma Intervention / Treatment: BIOLOGICAL: DEC-205/NY-ESO-1 Fusion Protein CDX-1401, DRUG: Epacadostat, OTHER: Laboratory Biomarker Analysis, OTHER: Pharmacological Study, DRUG: Poly ICLC Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Eligible patients will be women with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma after chemotherapy with no evidence of disease or minimal residual disease for primary or recurrent disease; this may or may not be measurable; these patients would normally enter a period of observation after standard management * Any human leukocyte antigen (HLA) type; (historic HLA typing is permitted) * Tumor expression of NY-ESO-1 or LAGE-1 by immunohistochemistry (IHC) and/or reverse transcriptase polymerase chain reaction (RTPCR) * Life expectancy > 6 months * Absolute neutrophil count (ANC) >= 1,000/uL * Platelets (PLT) >= 100,000/uL * Hemoglobin (Hgb) >= 8 g/dL * Total bilirubin =< 1.5 x upper limit of normal (ULN) * Serum aspartate aminotransferase (serum glutamic oxaloacetic transaminase [SGOT]/AST) or serum alanine aminotransferase (serum glutamate pyruvate transaminase [SGPT]/ALT) =< 3 x ULN * Serum creatinine =< 2 x ULN * Have been informed of other treatment options * Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure * Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 * The ability to swallow and retain oral medication * Patients of child-bearing potential must agree to use acceptable contraceptive methods (e.g., double barrier) during treatment * Patients may have received previous NY-ESO-1 vaccine therapy; patients who received maintenance paclitaxel or bevacizumab are eligible for enrollment provided they have discontinued therapy (at least 4 weeks for prior taxane or prior bevacizumab) prior to randomization and recovered from toxicities to less than grade 2 Exclusion Criteria: * Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may be available * Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders) * History of severe autoimmune disorders requiring use of steroids or other immunosuppressives * Concomitant systemic treatment with chronic use (based on the investigator's judgment) of corticosteroids, anti-histamine or non-steroidal anti-inflammatory drugs, and other platelet inhibitory agents * Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing of study drug (6 weeks for nitrosoureas); concomitant hormonal therapies for breast cancers are allowed * Subjects being treated with a monoamine oxidase inhibitor (MAOI), or drug which has significant MAOI activity (e.g., Meperidine, linezolid, methylene blue) within 3 weeks prior to screening * Subjects who are currently receiving therapy with a potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducer or inhibitor (e.g. clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir) * Use of UDP glucuronosyltransferase 1 family, polypeptide A9 (UGT1A9) inhibitor including: diclofenac, imipramine, and ketoconazole * Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dosing of study drug * Known hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) * Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study * Lack of availability of a patient for immunological and clinical follow-up assessment * Evidence of current drug or alcohol abuse or psychiatric impairment, which in the Investigator's opinion will prevent completion of the protocol therapy or follow-up * Pregnant or nursing female patients * Unwilling or unable to follow protocol requirements * Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug (i.e., any significant medical illness or abnormal laboratory finding that would, in the investigator's judgment, increase the patient's risk by participating in this study) * Known hypersensitivity to any of the study drugs that will be given to the participant * Additional exclusion criteria for exploratory cohort ONLY: Known pulmonary hypertension

NCT_ID NCT02166905

Study_NameDEC-205/NY-ESO-1 Fusion Protein CDX-1401, Poly ICLC, and IDO1 Inhibitor INCB024360 in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission

Study Objectives This is a 3-arm, parallel-group, active- and placebo-controlled, double-blind, randomized study, to compare treatment with intravenous custirsen at 640 mg (highest intended therapeutic dose) with placebo. The purpose of this study is to assess the effect of custirsen treatment on cardiac conduction and repolarization (electrical activity of the heart) in healthy subjects. The positive control employed to demonstrate assay sensitivity consists of a group receiving a single oral dose of 400 mg moxifloxacin on day 7. The moxifloxacin arm is un-blinded but the ECG readings are blinded. Conditions: Cardiac Conduction and Repolarization Intervention / Treatment: DRUG: Custirsen, DRUG: Placebo, DRUG: Moxifloxacin Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * The subject is a man aged 18 through 45 years with a body mass index (BMI) of 18 through 30 kg/m2 at screening. * The subject is in good health as determined by medical history, ECG, vital signs measurements, physical examination, and clinical laboratory tests. * The subject must be able to understand and comply with the requirements of the study (eg, all medication, dietary, exercise, tobacco, and alcohol restrictions). * The subject must provide written informed consent to participate in the study after reading the information and consent form, and after having an opportunity to discuss the study with the investigator or delegate. * Other inclusion criteria apply. Exclusion Criteria: * Exclusion criteria related to ECG findings include the following: * The subject has an ECG abnormality that may interfere with the accurate assessment of the QT interval, including intraventricular conduction delays (QRS >120 msec or PR >200 as measured at the screening and check-in visits) and complete or incomplete bundle branch blocks. * The subject has a resting QTcF interval of <=360 msec and/or >=450 msec measured at screening or day -2. * Exclusion criteria related to cardiac function include the following: * The subject has a known clinically significant (in the opinion of the investigator) cardiovascular disorder, including coronary artery disease, valvular heart disease, cardiomyopathies, or an ECG abnormality suggestive of prior myocardial infarction, angina pectoris, chamber enlargement, or hypertrophy. Notwithstanding, subjects with known significant disorders will be excluded. * The subject has a known clinically significant arrhythmia or rhythm disturbance observed on the screening and/or day -2 12-lead ECG. * The subject has a supine pulse rate outside of the range of 40 to 100 bpm (following at least a 10-minute rest) measured at screening or day -2. * The subject has a supine blood pressure outside of the range of 90 to 139 mm Hg systolic or 50 to 89 mm Hg diastolic (following at least a 10-minute rest) measured at screening and on day -2. Note: The blood pressure measurement may be repeated up to 3 times to meet eligibility requirements. In this case, the average of these 3 measurements must meet eligibility criteria. * The subject reports a history of, or risk factors for, Torsades de Pointes (eg, congestive heart failure, serum electrolyte abnormalities) including a family history of arrhythmia, sudden unexplained death at a young age (before 40 years) in a first-degree relative, or long QT syndrome, or a personal history of syncope. * The subject has low serum potassium and/or magnesium and/or corrected calcium blood levels (less than 3.5 milliequivalent/liter (mEq/L), 1.8 mEq/L, and 8.9 mg/dL, respectively) at screening and/or day-2. * The subject has any condition that may possibly interfere with drug absorption, distribution, metabolism, or excretion (eg, previous surgery on the gastrointestinal tract [including removal of parts of stomach, bowel, liver, gall bladder, or pancreas] or stomach banding). * The subject has an abnormality in medical history, physical examination, biochemistry, hematology, coagulation, serology, or urinalysis at the screening or admission visit that is considered clinically significant by the investigator or meets grades 2 <= age <= 4 Common Terminology Criteria for Adverse Events (CTCAE) v.4 criteria, or in the opinion of the investigator, could interfere with the objective of the study or the safety of the subject. Notwithstanding, the following values must remain within the normal range values (as determined by the Physician Reference Laboratory [PRL]) in order for a subject to be eligible for the study: calcium, magnesium, potassium, creatinine, ALT, AST, GGT, hemoglobin, absolute lymphocyte count, absolute 50 mg/dL in asymptomatic subjects and absolute leukocyte count values as low as 3.1x109/L in African American subjects will be considered for enrollment at the investigator's discretion. Lastly, the upper limit value for exclusion is modified for the following values and is as follows: INR>1.2, total bilirubin>1.2 mg/dL, serum amylase >143 U/L, LDH>261 U/L, and CPK>367 U/L, which do not normalize upon repeat testing, will be exclusionary. * The subject has used one of the prohibited drugs, substances or foods as follows: * any investigational product within 60 days (or 5 half-lives, whichever is longer) preceding the study * any prescription or nonprescription medication (including herbal remedies, vitamins, or dietary supplements) or vaccine within 14 days of the first day of study drug administration (day 1) or within 5 half-lives before the first day of study drug administration, whichever is longer. Exceptions are locally acting medications (eg, topical creams), which are not allowed within 5 days of study drug administration, and the occasional use of acetaminophen (up to 3 g/day) and ibuprofen (up to 1200 mg/day). * consumption of grapefruit, grapefruit juice, Seville oranges, pomelo-containing products, within the 14 days prior to day -1 and then throughout the entire study * consumption of excessive amounts of alcoholic beverages, defined as more than 3 drinks per day (beer, wine, or distilled spirits), or unwillingness to comply with the restricted use of alcohol during the study (96 hours prior to admission and until 48 hours after the last study drug administration), history of alcoholism, or evidence of drug/chemical abuse * positive urine drug (cocaine, amphetamines, barbiturates, opiates, phencyclidine, benzodiazepines, tetrahydrocannabinol), cotinine, or alcohol screen at the screening visit or admission * consumption of quinine (eg, tonic water) within 7 days prior to admission * The subject has any other condition, which, in the opinion of the investigator, makes the subject inappropriate for the study. * Other exclusion criteria apply.

NCT_ID NCT01874561

Study_NameThorough QT/QTc (Corrected QT Interval) Study to Evaluate the Effect of Custirsen on Cardiac Repolarization

Study Objectives Describe the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of irinotecan in cancer patients with advanced solid tumors with UGT1A1 6/6 and 6/7 genotypes. Conditions: Advanced Cancer Intervention / Treatment: DRUG: Irinotecan Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed solid tumor or lymphoma that is appropriate for treatment with irinotecan. * >= 18 years * ECOG performance status 0 <= age <= 1 * Life expectancy of greater than 12 weeks. * Normal organ and marrow function as defined below: * leukocytes >= 3,000/μl * absolute neutrophil count >= 1,500/μl * platelets >= 100,000/μl * total bilirubin within normal institutional limits * AST(SGOT)/ALT(SGPT) <= 2.5 X institutional ULN (<=5 X ULN in patients with hepatic metastases) * creatinine within normal institutional limits OR * glomerular filtration rate >=50 ml/min/1.73 m2 for patients with creatinine levels above institutional normal as calculated by the modified MDRD equation recommended by the National Kidney Disease Education Program * Measurable or assessable disease. * Able to understand and the willing to sign a written informed consent document. * Women of child-bearing potential and men and their partners must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. * Patients with UGT1A1 genotype 6/6, 6/7, and 7/7. Patients with either one or two of the rare alleles (i.e., 5 allele and 8 allele), and carriers of the *6 allele will not be enrolled in the study. Patients will have blood drawn for genotyping upon signing the informed consent form for this study. * Patients taking any statin therapy should interrupt the dosing of the statin for the 3 days before and after the administration of irinotecan at each cycle Exclusion Criteria: * Biologic therapy, chemotherapy, radiotherapy, or investigational agent within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. * Cannot be receiving any other investigational agents. * Use of colony growth factor within 3 week prior to study entry. * Post-transplant patients, as they may be subject to severe neutropenia. * Uncontrolled brain metastases. Patients with brain metastases must have stable neurologic status off of steroids and anticonvulsants for at least 4 weeks and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant women are excluded from this study because irinotecan is an agent with the potential for teratogenic or abortifacient effects. Breastfeeding should be stopped. * HIV-positive patients, as patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. * History of inflammatory bowel disease requiring therapy or patients with chronic diarrhea syndromes or paralytic ileus. * Patients who have undergone a major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to start of therapy cannot participate. * Patients with prior pelvic irradiation cannot participate.

NCT_ID NCT00708773

Study_NameGenotype-Directed Dose-Escalation Study of Irinotecan in Patients With Advanced Solid Tumors

Study Objectives This trial is a single-center, single-dose, double-blind, parallel-group, randomized, 3-arm PK trial in healthy male volunteers comparing a biosimilar pertuzumab (EG1206A) to a single intravenous (i.v.) infusion to both European Union (EU) and United States of America (US) reference products. Conditions: Breast Cancer Intervention / Treatment: DRUG: 420 mg EG1206A EirGenix Pertuzumab in 14 mL Injection, DRUG: Perjeta (EU origin) 420 mg in 14 mL Injection, DRUG: Perjeta (US origin) 420 mg in 14 mL Injection Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * aged 18 <= age <= 55 * overtly healthy as determined by medical evaluation * Body weight of at least 50 kg and not higher than 105 kg at screening * BMI above/equal to 18.0 and below/equal to 30.0 kg/m2 at screening * Male * Agrees to the following during the treatment period and until 3 months after administration: * Be and remain abstinent from heterosexual intercourse OR agree to use a male condom and female partners of childbearing potential must use an additional highly effective contraceptive method * Abstain from donating sperm. * Signed informed consent * Valid COVID-19 immunization status as per current regulations Exclusion Criteria: * History or evidence of any clinically relevant disease, as judged by the investigator * Any medical disorder, condition, or history of such that would impair the participant's ability to participate or complete this trial in the opinion of the investigator * Pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination, and effects of the IMP will not be normal * Known or suspected hypersensitivity to the IMPs (active substances, or excipients of the preparations) * Known severe allergies e.g., allergies to more than 3 allergens * Relevant diseases within the last 4 weeks before IMP administration * Febrile illness within 2 weeks before IMP administration. * History of known or suspected malignant tumors * Known or suspected disorder of the liver * Use of systemic/topical medicines/substances which oppose the trial objectives, or which might influence them within 4 weeks before IMP administration * Regular use of therapeutic or recreational drugs or supplements * Use of any herbal products or St. John's wort from 4 weeks before IMP administration * Prior treatment with pertuzumab * Smoking * History of alcohol or drug abuse * Regular daily consumption of more than 500 mL of usual beer or the equivalent quantity of approximately 20 g of alcohol in another form * Intake of alcohol containing food and beverages from 48 h prior to admission to the ward * Regular daily consumption of more than 1 L of methylxanthine-containing beverages * Excluded physical therapies that might alter the PK or safety results of the trial from 7 days before IMP administration until follow-up * Strenuous physical exercise or sauna visit with 72 h before admission to the ward * Donation of more than 100 mL of whole blood or plasma within 4 weeks or approximately 500 mL whole blood within 3 months before IMP administration * Plasmapheresis within 3 months before IMP administration * Previous or concomitant participation in another clinical trial with IMP(s) * Clinically relevant findings in the ECG * LVEF below 55% * Systolic blood pressure below 100 mmHg or above 140 mmHg * Diastolic blood pressure below 50 mmHg or above 90 mmHg * Heart rate below 50 beats/ min or above 90 beats/min * Clinically relevant findings in the physical examination that may affect the objectives of the trial, or the safety of the participant * Poor venous access * Clinically relevant deviations of the screened safety laboratory parameters * Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase, or total bilirubin above 1.2 upper limit of normal * Thyroid disorders as evidenced by assessment of thyroid stimulating hormone (TSH) level outside the normal reference range * Positive results for hepatitis B virus surface antigen, hepatitis C virus antibodies, human immune deficiency virus antibodies, and human immune deficiency virus antigen * Positive urine drug test * Positive alcohol test * Positive cotinine test * Any criteria which, in the opinion of the investigator, preclude participation for scientific reasons, for reasons of compliance, or for reasons of the participant's safety * Close affiliation with the investigational site * Vulnerable participants who are e.g., institutionalized due to regulatory or juridical order dependent on sponsor, site, or investigator or not able to consent, respectively. * History of COVID-19 within 2 months prior to screening * Long COVID-19 syndrome or other clinically relevant COVID-19 related symptoms or sequelae * Positive SARS-CoV-2 viral ribonucleic acid (RNA) test at admission * No SARS-CoV-2 vaccinations should be booked within 14 days before IMP administration and until last trial visit.

NCT_ID NCT05471648

Study_NameA Pharmacokinetic Study Comparing EG1206A and Perjeta (Pertzumab) in Healthy Male Volunteers

Study Objectives A pre-surgery study to assess changes that occur in human breast cancer material and normal skin after a short course of treatment with Iressa. Conditions: Breast Cancer Intervention / Treatment: DRUG: Gefitinib Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Invasive breast cancer, Aged >= 18 years, Not more than 28 days from initial diagnosis Exclusion Criteria: * Pregnant or lactating patients, Prior or current radiotherapy for breast cancer, Known allergy reaction to Iressa

NCT_ID NCT00637026

Study_NamePh II Early BC Pre-Surgical Biologic Study

Study Objectives The purpose of this study is to evaluate the effectiveness of the investigational radioisotope Radium-223, Alpharadin, in treatment of men with prostate cancer and bone metastases that no longer respond to hormonal treatment. Conditions: Prostate Cancer, Neoplasm Metastasis Intervention / Treatment: DRUG: Radium-223 dichloride (BAY88-8223) Location: United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Histologically or cytologically confirmed adenocarcinoma of the prostate. * Hormone refractory with evidence of rising PSA: * Patient must be maintained on androgen ablation therapy with LHRH agonist (stable dose for at least 8 weeks prior to study entry), or have undergone orchiectomy * Serum testosterone level is required to be <= 50 ng/dl * Patients who have received prior hormonal drug therapy: * Flutamide, nilutamide or cyproterone acetate must have stopped at least four weeks prior to study drug administration and progression must have been demonstrated since cessation; * Bicalutamide must have stopped at least six weeks prior to study drug administration and progression must have been demonstrated since cessation * Elevated and rising PSA: * Baseline PSA level >= 10 ng/ml * Progressive rise in PSA, defined as two consecutive increases in PSA documented over a previous reference value (measure 1). The first increase in PSA (measure 2) should occur a minimum of 1 week from the reference value (measure 1. This increase in PSA should be confirmed (measure 3) after a minimum of 1 week. If the confirmatory PSA value (measure 3) is less than the previous value, the patient will still be eligible provided the next PSA measure (measure 4)is found to be greater than the second PSA value(measure 2).3. Multifocal skeletal metastases confirmed by bone scintigraphy within the last 6 weeks * Performance status: ECOG 0 <= age <= 2 * Life expectancy: At least 6 months * Laboratory requirements: * Neutrophil count >= 1.5 x 109/L * Platelet count >= 100 x109/L * Haemoglobin >= 95 g/L * Total bilirubin level within normal institutional limits * ASAT and ALAT <= 2,5 times upper institutional limit of the normal range * The patient is willing and able to comply with the protocol (including maintenance of patient diary), and agrees to return to the hospital for follow-up visits and examination * The patient has been fully informed about the study and has signed the informed consent form Exclusion Criteria: * Has received an investigational drug within 4 weeks prior to the administration of radium-223, or is scheduled to receive one during the treatment and post-treatment period * Has received chemo-, immunotherapy, or external radiotherapy within the last 4 weeks prior to administration of study drug, or has not recovered from adverse events due to agents administered more than 4 weeks earlier * More than one regimen of previous cytotoxic chemotherapy * Has received prior hemibody external radiotherapy * Has a need for immediate external radiotherapy * Has received systemic radiotherapy with strontium-89, samarium-153, rhenium-186 or rhenium-188 for the treatment of bony metastases within the last year prior to administration of study drug * Has started treatment with bisphosphonates less than 3 months prior to administration of study drug. Patients are allowed to be on bisphosphonates provided patient is on a stable dose for >= 12 weeks before administration of study drug. * Patients who are <= 4 weeks (6 weeks for bicalutamide) post withdrawal of antiandrogen therapy * Patients who have started or stopped systemic steroids, within a week prior to study drug administration * Other currently active (relapse within the last 3 years) malignancy (except non-melanoma skin cancer) that are not prostate cancer metastases * Visceral metastases from prostate cancer as assessed by abdominal/pelvic CT or MRI within six weeks before administration of study drug; Lung lesions from prostate cancer as assessed by chest X-ray within 6 weeks. This requirement does not include abdominal or pelvic lymph node involvement (individual lymph node size must not exceed 1 cm in short diameter) which is acceptable * Bulky loco-regional disease * Any other serious illness or medical condition, for example: * any uncontrolled infection * any patient who has clinical heart failure severe enough to cause marked limitation of activity, and who is only comfortable at rest; or any patient who has heart failure more severe than this (NYHA Heart Failure Class III or IV * Crohns disease or ulcerative colitis

NCT_ID NCT00337155

Study_NameBAY88-8223, Dose Finding Study in Patients With HRPC

Study Objectives The primary objective of the clinical study is to evaluate, in patients who experience a first or second relapse of their multiple myeloma, the safety of escalating doses of IPH2101 combined with lenalidomide Conditions: Patients With Multiple Myeloma Experiencing a, First or Second Relapse Intervention / Treatment: DRUG: IPH2101 combined to lenalidomide Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Signed informed consent obtained before any trial-related activities * Progressive disease or relapse of multiple myeloma (according to the IMWG definition) after one or two prior therapeutic treatments or regimens for multiple myeloma that achieved a response duration of at least 6 months * Prior therapeutic treatment regimens may have included Thalidomide and Lenalidomide. Regarding patients previously treated by Lenalidomide, only patients who achieved at least Partial Response duration of at least 6 months can be included. The patient must not have discontinued treatment due to Lenalidomide intolerance. * Measurable disease, as indicated by one or more of the following: * Serum M-protein >= 0.5 g/dL If Serum Protein Electrophoresis is felt to be unreliable for routine M-protein measurement (particularly for patients with IgA MM), then quantitative immunoglobulin levels can be accepted). * Urine Bence-Jones protein >= 200 mg/24 h * Involved serum Free Light Chains (sFLC) level >= 10 mg/dl ( >= 100 mg/l) provided sFLC ratio is abnormal (<0.26 or >1.65) * ECOG performance status of 0, 1 or 2 * Clinical laboratory values at screening * Calculated creatinine clearance (according to MDRD) > 60 ml/min * Platelet >= 75 x 109 /l for patients with < 50% BM plasma cells, and >= 30 x 109 /l for patients with > 50% BM plasma cells * ANC > 1 x 109 /l * Bilirubin levels < 1.5 ULN ; ALT and AST < 3 ULN (grade 1 NCI) * Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing Lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking Lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy * All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®. Exclusion Criteria: * Age < 18 years or > 80 years * Non secreting multiple myeloma or non measurable disease (< 0.5 g /dL M-Protein in serum or < 200 mg urinary M-protein / 24 h or <10 mg/dl involved sFLC) * Life-threatening conditions related or not to MM relapse * Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking Lenalidomide) * Known hypersensitivity to thalidomide or IMiD®. * Use of any investigational agent within the last month * Treatment by systemic corticosteroids (except inhaled corticosteroids) or chemotherapy (including consolidation and maintenance) within the last month (use of biphosphonates is permitted) * Radiotherapy within the last month * Primary or associated amyloidosis * Peripheral neuropathy of grade >= 3 according to the CTCAE of the NCI * Abnormal cardiac status with any of the following * NYHA stage III or IV congestive heart failure * myocardial infarction within the previous 6 months * cardiac arrhythmia remaining symptomatic despite treatment * Current active infectious disease or positive serology for HIV, HCV or positive Hbs Antigen * History of or current auto-immune disease * History of other active malignancy within the past 5 years (apart from basal cell carcinoma of the skin, or in situ cervix carcinoma) * Serious concurrent uncontrolled medical disorder * History of allograft or solid organ transplantation * Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule * Inability to comply with an antithrombotic regimen

NCT_ID NCT01217203

Study_NameStudy on the Safety, Anti-tumor Activity and Pharmacology of IPH2101 Combined With Lenalidomide in Patients With Multiple Myeloma Experiencing a First or Second Relapse

Study Objectives The purpose of this randomized, double-blind, placebo-controlled study is to determine the safety and efficacy of pracinostat compared to placebo when combined with azacitidine, and FDA approved treatment for Myelodysplastic Syndrome (MDS). Conditions: Myelodysplastic Syndrome Intervention / Treatment: DRUG: pracinostat, DRUG: Placebo, DRUG: Azacitidine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * Voluntary written informed consent * Histologically or cytologically documented diagnosis of MDS (any French-American-British [FAB] classification subtype; that is classified as intermediate 2 (1.5 to 2.0 points) or high risk (>=2.5 points) according to the International Prognostic Scoring System risk category, with >5% and <30% blasts, and a peripheral blast count of <20,000 * Bone marrow aspirate smears and bone marrow biopsies within 28 days of first study treatment * There must be a clinical indication for treatment with azacitidine. * Previously untreated with hypomethylating agents (prior therapy with transfusions, hematopoietic growth factors, or immunosuppressive therapy is allowed) * Eastern Cooperative Oncology Group performance status of 0, 1, or 2 * Adequate organ function as evidenced by: 1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=2.5 x the upper limit of normal (ULN) (<=5 x ULN for patients with hepatic metastases 2. Total bilirubin <=1.5 x ULN or total bilirubin of 2, whichever is higher 3. Serum creatinine <2 mg/dL, or creatinine clearance <=1.5 x ULN 4. QTcF interval <=470 msec * Female or male patients >=18 years-of-age * Male patients who are surgically sterile or willing to use adequate contraceptive measures or abstain from heterosexual intercourse during the entire study treatment period * Female patients who are surgically sterile or post menopausal or female patients who are not of child-bearing potential and female patients of child-bearing potential who agree to use adequate contraceptive measures or abstain from intercourse during the study treatment period, who are not breastfeeding, and who have had a negative serum pregnancy test <=7 days prior to first study treatment. * Willingness and ability to comply with the trial and follow-up procedures Exclusion Criteria: * Received any of the following within the specified time frame prior to administration of study medication: 1. Any investigational agent within 14 days or 5 half-lives prior to first study treatment, whichever is longer 2. Previous therapy for malignancy within 21 days prior to first study treatment, including any chemotherapy, immunotherapy, biological or hormonal therapy (6 weeks for nitrosoureas or mitomycin C) 3. Hydroxyurea within 48 hours prior to first study treatment 4. Hematopoietic growth factors: erythropoietin, granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), or thrombopoietin receptor agonists at least 7 days (14 days for Aranesp) prior to study enrollment 5. Major surgery within 4 weeks prior to first study treatment * Patients that have not recovered from side effects of previous therapy * Cardiopulmonary function exclusion: 1. Current unstable arrhythmia requiring treatment 2. History of symptomatic congestive heart failure (New York Heart Association Classes III or IV) 3. History of myocardial infarction within 6 months of enrollment 4. Current unstable angina * Concomitant treatment with histone deacetylase (HDAC) inhibitors or drugs with significant action as HDAC inhibitors, such as valproic acid, is not permitted * Clinical evidence of central nervous system involvement * Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis). * Active infection with HIV or chronic hepatitis B or C * Life-threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with participation in this study * Presence of a malignant disease within the last 12 months, with the exception of adequately treated in-situ carcinomas, basal or squamous cell carcinoma, or non-melanomatous skin cancer * Inability (including psychological, familial, sociological, or geographical conditions) to comply with trial and/or follow-up procedures

NCT_ID NCT01873703

Study_NamePhase 2 Study of Pracinostat With Azacitidine in Patients With Previously Untreated Myelodysplastic Syndrome

Study Objectives A phase II study to evaluate the combination of Lenalidomide and Rituximab as front line therapy for the treatment of elderly frail patients evaluated in CGA with Diffuse Large B-cells non-Hodgkin Lymphoma. Conditions: Diffuse Large B-cells Non-Hodgkin Lymphoma Intervention / Treatment: DRUG: Rituximab-Dexamethasone-Lenalidomide Location: Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically proven CD20 positive Diffuse Large B-cell Lymphoma according to WHO classification (local pathologist) * Age >= 70 years * Previously untreated * CGA assessment performed before starting treatment * FRAIL patients defined as follows Age > 80 years (with UNFIT profile): ADL >= 5 residual functions and/or IADL >= 6 residual functions and/or CIRS: 0 comorbidity of grade 3 <= age <= 4 and 5 <= age <= 8 comorbidities of grade 2 Age < 80 (ONLY one of the following criteria): ADL <= 4 residual functions IADL <= 5 residual functions CIRS: 1 comorbidity of grade 3 <= age <= 4 or > 8 comorbidities of grade 2 * Ann Arbor Stage I - IV (Appendix F) * At least one bi-dimensionally measurable lesion defined as > 1.5 cm in its largest dimension on CT scan * ECOG performance status of 0- 3 (Appendix E) * No active hepatitis C virus (HCV) infection. In case of HCV positivity HCV-RNA is required. Only patients with HCV-RNA negative are accepted. * Adequate hematologic function (unless caused by bone marrow infiltrate), defined as follows: * Hemoglobin > 10 g/dL * WBC > 2500/mmc with PMN > 1000/ mmc * Platelets count >= 75000/mmc * Creatinine clearance >= 10 mL/min * Ability and willingness to comply with the study protocol procedure * Life expectancy > 6 months * Patients must give written informed consent. * Male subjects must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following investigational product discontinuation, even if he has undergone a successful vasectomy. Exclusion Criteria: * Histological diagnosis different from CD20 positive Diffuse Large B-cell Lymphoma are excluded. * Previous exposure to cytotoxic agents * Suspect or clinical evidence of CNS involvement by lymphoma * Contraindication to the use of Rituximab or of Lenalidomide * HBsAg positivity; HBsAg-negative patients with anti-HBc antibody can be enrolled if Hepatitis B Virus (HBV)-DNA are negative and antiviral treatment with Lamivudine or Tenofir is provided. * HIV positivity * Active herpes zoster infection; previously infected patients is accepted only with concomitant treatment with Valacyclovir. * Any history of other malignancies within 5 years prior to study entry except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer * AST /ALT > 2 x UNL; bilirubin > 2 x UNL; serum creatinine > 2.5 mg /dL * Creatinine clearance < 10 mL/min * Evidence of any severe active acute or chronic infection * Severe cardiac dysfunction (NYHA grade III-IV) * Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent * Absence of caregivers in non-autonomous patients

NCT_ID NCT02955823

Study_NameA Phase II Study of the FIL on Elderly Frail Patients With DLBCL

Study Objectives This phase II trial studies the effect of a vaccine called CDX-1401 given with or without a biologic drug called CDX-301 in treating patients with stage IIB-IV melanoma. The cancer vaccine CDX-1401 attaches to a protein that is made in tumor cells. The vaccine helps the body recognize the tumor to fight the cancer. The biologic drug CDX-301 may help the body make more of the tumor fighting cells, known as dendritic cells. Another biologic drug, poly-ICLC, may stimulate the immune system and help these dendritic cells mature so that they can recognize the tumor. Giving CDX-301 may make the immune response to a combination of CDX-1401 and poly-ICLC better. Conditions: Cutaneous Melanoma, Melanoma, Melanoma of Unknown Primary, Mucosal Melanoma, Ocular Melanoma, Stage IIB Cutaneous Melanoma AJCC v6 and v7, Stage IIC Cutaneous Melanoma AJCC v6 and v7, Stage III Cutaneous Melanoma AJCC v7, Stage IIIA Cutaneous Melanoma AJCC v7, Stage IIIB Cutaneous Melanoma AJCC v7, Stage IIIC Cutaneous Melanoma AJCC v7, Stage IV Cutaneous Melanoma AJCC v6 and v7 Intervention / Treatment: BIOLOGICAL: DEC-205/NY-ESO-1 Fusion Protein CDX-1401, DRUG: Poly ICLC, BIOLOGICAL: Recombinant Flt3 Ligand Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patients with fully resected stage IIb through IV melanoma, with melanoma validated by histology or cytology, who have NOT received prior therapy. * Patients may have had primary cutaneous, mucosal, or ocular melanoma or metastasis from an unknown primary site. * Tissue should be submitted for evaluation of NY-ESO-1 expression and T-cell infiltrates. However, availability of tissue and/or positivity for NY-ESO-1 is not mandatory. * Prior radiation, chemotherapy or biologics NOT allowed * Not currently receiving any anticancer therapy * Age >= 18 years * Because no dosing or adverse event (AE) data are currently available on the use of CDX-1401 or CDX-301 in patients < 18 years, children are excluded from this study, but will be eligible for future pediatric trials. * Eastern Cooperative Oncology Group (ECOG) performance score of 0 <= age <= 1 * Life expectancy of at least 6 months * Leukocytes >= 3,000/mcL * Absolute neutrophil count >= 1,000/mcL * Platelets >= 75,000/mcL * Hemoglobin > 9 g/dL * Total bilirubin < 1.5 x institutional upper limit of normal (bilirubin < 3 x institutional upper limit of normal for Gilbert's syndrome) * Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal * Creatinine < 1.5 x institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal * The first six patients enrolled in the Flt3L arm of the study cannot be human immunodeficiency virus (HIV)-positive. After the evaluation of safety in the first 6 patients, HIV-positive patients with adequate immune function as evidenced by stable CD4 counts >= 350/mm^3 are allowed to participate if the following criteria are met: * maintained on stable antiretroviral therapy with no significant drug interactions, and * no recent history of acquired immunodeficiency syndrome (AIDS) indicator conditions (> 2 years from enrolling in trial), and * physician providing patient's care for HIV must also approve of patient entering the study * Females of childbearing potential must have a negative pregnancy test within 7 days before the initiation of protocol therapy. * The effects of CDX-1401 or CDX-301 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) before study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception before the study, for the duration of study participation, and 4 months after completion of CDX-1401 or CDX-301 administration. * NOTE: Subjects are considered not of child-bearing potential if they are surgically sterile, they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy, or they are postmenopausal. Menopause is the age associated with complete cessation of menstrual cycles, menses, and implies the loss of reproductive potential. By a practical definition, it assumes menopause after 1 year without menses with an appropriate clinical profile at the appropriate age. * Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * Patients who have had cytotoxic chemotherapy, radiotherapy, interferon (IFN), or ipilimumab before entering the study * Immunosuppressive therapy within 30 days prior to initiation of protocol therapy * Steroid therapy, or steroid therapy with more than 7 consecutive days of steroids within the prior 4 weeks * The use of prednisone or equivalent < 0.125 mg/kg/day (absolute maximum of 10 mg/day) as replacement therapy is permitted * Inhaled or topical corticosteroids are permitted * Patients who are receiving any other investigational agents * Current or history of systemic autoimmune disease requiring systemic therapy. * NOTE: The following will not be exclusionary: * The presence of laboratory evidence of autoimmune disease (e.g., positive antinuclear antibody [ANA] titer) without associated symptoms * Clinical evidence of vitiligo * Other forms of depigmenting illness * Cardiovascular disease that meets one of the following: congestive heart failure (New York Heart Association Class III or IV), active angina pectoris, or recent myocardial infarction (within the last 6 months) * Cirrhosis or chronic hepatitis C virus positivity or chronic hepatitis B infection * NOTE: A positive hepatitis B serology indicative of previous immunization (i.e., hepatitis B virus surface antibody [HBsAb]-positive and hepatitis B virus core antibody [HBcAb]-negative), or a fully resolved acute hepatitis B virus infection is not an exclusion criterion * Known history of immunodeficiency disorder other than HIV-positive status * Extensive active brain disease including symptomatic brain metastases or presence of leptomeningeal disease * NOTE: Patients with brain metastasis, after definitive therapy with surgery or stereotactic radiation and stable off steroids for >= 4 weeks, are eligible * Other invasive cancers that are clinically active * Pregnancy or nursing or unwilling to take adequate birth control during therapy * NOTE: Pregnant women are excluded from this study because CDX-1401 or CDX-301 and poly-ICLC have an unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CDX-1401 or CDX-301, breastfeeding should be discontinued if the mother is treated with CDX-1401 or CDX-301 and poly-ICLC * History of allergic reactions attributed to compounds of similar chemical or biologic composition to CDX-1401 or CDX-301 or poly-ICLC * Prior organ allograft or allogeneic transplantation, if the transplanted tissue is still in place * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Medical or psychiatric illness that would, in the opinion of the investigator, preclude participation in the study or the ability of patients to provide informed consent for themselves * History of pulmonary disease such as emphysema or chronic obstructive pulmonary disease (COPD) (forced expiratory volume in 1 second [FEV1] < 60% of predicted for height and age). Pulmonary function tests (PFTs) are required in patients with prolonged smoking history or symptoms of respiratory dysfunction * Vaccinations other than those given as part of this research study (with the exception of influenza vaccine) are prohibited throughout the duration of study participation. * NOTE: Influenza vaccination (inactivated) is permitted during the flu season. The preferred time is 7 to 14 days after CDX-1401 administration

NCT_ID NCT02129075

Study_NameA Vaccine (CDX-1401) With or Without a Biologic Drug (CDX-301) for the Treatment of Patients With Stage IIB-IV Melanoma

Study Objectives To evaluate the efficacy and safety of Huaier Granule for prevention of recurrence and metastasis of hepatocarcinoma after radical hepatectomy. Conditions: Hepatic Carcinoma Intervention / Treatment: DRUG: Huaier Granule Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Age: >= 18 and <= 75 years, both male and female; * Radical hepatectomy has been performed for hepatocellular carcinoma; * The hepatocellular carcinoma has been confirmed by pathological examination; * Barcelona clinic liver cancer(BCLC) stage A or B; * Not receiving any preoperative anticancer drug; * The liver and kidney function satisfies the following conditions within 15 days after surgery (excluding day 15): aspartate aminotransferase(AST), glutamic-oxalacetic transaminase(ALT)<3 upper limit of normal(ULN), total bilirubin<=2ULN, serum creatinine <1.5 ULN; * Other laboratory tests meet the following requirements within 15 days after surgery (excluding day 15): Hb>=9g/dl, platelet count>=60×109/L, absolute neutrophil count>1.0×109/L; * The expected survival time >= 12 weeks; * The subjects volunteer to sign the informed consent. Exclusion Criteria: * Hepatocellular carcinoma patients who received non-radical hepatectomy; * Non-hepatocellular carcinoma patients; * Those with Child-Pugh C; * Pregnant or lactating women; * Those with active bleeding due to various reasons; * Those with HIV infection or AIDS-associated diseases; * Those with severe acute and chronic diseases; * Those with severe diabetes; * Those with serious infectious diseases; * Those who can not take drugs by oral route; * Drug abusers or those with psychological or mental diseases that may interfere with study compliance; * Conditions that are considered not suitable for this study investigators

NCT_ID NCT01770431

Study_NameHuaier Granule for Prevention of Recurrence and Metastasis of Hepatocarcinoma After Radical Hepatectomy

Study Objectives This is a prospective, Phase IV, multi-center, single arm, open-label, interventional study to evaluate the safety of trastuzumab for the treatment of human epidermal growth factor receptor 2 protein (HER2)-positive node positive or high risk node negative breast cancer participants with regimen consisting of doxorubicin and cyclophosphamide followed by either paclitaxel or docetaxel (AC-TH Regimen) or a regimen consisting of docetaxel and carboplatin (TCH Regimen) in Indian population. Conditions: Breast Cancer Intervention / Treatment: DRUG: Carboplatin, DRUG: Cyclophosphamide, DRUG: Docetaxel, DRUG: Doxorubicin, DRUG: Paclitaxel, DRUG: Trastuzumab Location: India Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed early invasive HER2 positive, node positive or high risk node negative breast cancer with no evidence of residual, locally recurrent or metastatic disease and defined as clinical stage I to IIIA that is eligible for adjuvant treatment with trastuzumab * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 * HER2 over expression/amplification defined as either Immunohistochemistry (IHC)3+, or IHC2+ and Fluorescence in situ Hybridization (FISH) positive as determined in a central laboratory * At time of starting trastuzumab therapy, LVEF measured by echocardiography * Screening LVEF greater than or equal to (>=) 55 percent (%) * Adequate bone marrow, renal, and hepatic function * Agreement to use an adequate, non-hormonal means of contraception by women of childbearing potential Exclusion Criteria: * Any contraindication to trastuzumab * Previous adjuvant breast cancer treatment with an approved or investigational anti-HER2 agent * History of other malignancy, except for curatively treated carcinoma in situ of the cervix or basal cell carcinoma and participants with other curatively treated malignancies who have been disease-free for at least 5 years * Past history of ductal carcinoma in situ and/or lobular carcinoma that has been treated with any systemic therapy or with radiation therapy to the ipsilateral breast where the invasive cancer subsequently develops * Locally advanced (Stage IIIB and IIIC) and metastatic disease (Stage IV) * Clinically relevant cardiovascular disorder or disease * Uncontrolled hypertension, or history of hypertensive crisis or hypertensive encephalopathy * History of severe allergic or immunological reactions, example difficult to control asthma * Pregnant or lactating women

NCT_ID NCT02419742

Study_NameSafety and Efficacy of Trastuzumab as Part of Breast Cancer Treatment Regimen

Study Objectives This study is designed to assess the efficacy and safety of DTA-H19/PEI given as six intravesical instillations of 20 mg of plasmid DNA complexed with PEI into the bladder of patients with intermediate risk superficial bladder cancer \[recurrent stages Ta (low or high grade)and T1, (low grade) transitional cell carcinoma (TCC)\] who have failed prior intravesical therapies including either Bacillus Calmette-Guérin (BCG) or chemotherapy. The primary efficacy objective is to determine the effect of DTA-H19/PEI on the prevention of new tumors after the induction course of 6 weekly intravesical administrations of investigational product assessed 8 to 10 weeks after the start of treatment. Secondary objectives include assessing the ablative effect of DTA-H19/PEI on a marker tumor, safety assessed by the incidence and severity of adverse events, determining the long-term (46 weeks) continued rates of absence of bladder cancer, and time to tumor recurrence in those patients who had a complete response (CR) after the induction course. Conditions: Superficial Bladder Cancer Intervention / Treatment: BIOLOGICAL: BC-819/PEI Location: Israel, United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: To be eligible to participate in this study, patients must: * Provide written informed consent. * Have intermediate-risk recurrent superficial TCC of the bladder defined as Stage Ta (low or high grade) or T1 (but with penetration into no more than ½ of the lamina propria), low grade (grade 1 or grade 2), as confirmed by histopathology, and have not recurred within 3-months of a complete course of a prior acceptable therapy (i.e., 6-weekly intravesical administrations of BCG or standard adjuvant treatment with thiotepa, doxorubicin, epirubicin, valrubicin, or mitomycin C). * Have complete resection of all papillary tumors with the exception of a single superficial papillary tumor that is appropriate to be a marker tumor (<1 cm in diameter). * Have >= 2 tumor and <= 7 tumors visible during cystoscopy and no tumor larger than 3 cm in diameter. If only one tumor is present, it must be large enough to obtain a biopsy specimen adequate to determine the tumor stage and grade and leave a marker tumor. * Have at least one tumor specimen resected before the start of the study that was positive for H19 expression by ISH. H19 expression positive is defined as >= 60 % of the tumor cells in the specimen expressing H19 at a moderate staining intensity. * Have failed at least one prior standard intravesical treatment including chemotherapy with mitomycin C, thiotepa, valrubicin, doxyrubicin, or epirubicin, or immunotherapy with BCG. Failure after treatment with chemotherapy is defined as recurrent disease after at least one intravesical instillation of drug. Failure after treatment with BCG is defined as intolerance to treatment such that treatment was discontinued or after having received 6 or more BCG instillations there is recurrent or persistent disease 3 or more months after initiation of BCG treatment. * Have a Karnofsky's performance status of greater than or equal to 60%. * Have adequate bone marrow reserve: Hemoglobin > 10 g/dL, WBC greater than or equal to 3000/mm3, and platelets > 100,000 /mm3. * Have adequate renal function with serum creatinine < 1.5 x the laboratory upper limit of normal (ULN). * Have adequate liver function with serum biliru¬bin, AST/SGOT and ALT/SGPT < 2 times the laboratory ULN. * Be at least 18 years. * If male, agree to use a condom, if sexually active, and if female, agree to practice one of the acceptable methods of birth control or be surgically sterile or postmenopausal (greater than 1 year post last menstrual cycle. Exclusion Criteria: To be eligible to participate in this study, patients must not: * Have current diagnosis or history of Stage T1 (high grade) or Stage T2 or higher or CIS. * Have severe concomitant disease that might limit compliance or completion of the protocol. * Have a tumor in a diverticulum, in the prostatic urethra, or covering the ureteral orifice. * Have any other malignancy that might impact 5-year survival or might be potentially confused with TCC. * Have congenital or acquired immune deficiencies. * Be receiving cytotoxic drugs or corticosteroids. * Have received intravesical therapy within 8 weeks prior to study entry. * Have received radiation therapy for their bladder cancer at any time or any other conditions including pelvic irradiation for any condition within 4 months prior to study entry. * Have active infections (including urinary tract infections) defined as viral, bacterial, or fungal infections requiring therapy, HIV-positive status, concurrent febrile illness, or gross hematuria. * Have biopsy, TUR, or traumatic catheterization within 14 days of start of treatment. * If female, be pregnant or breast feeding. * Have participated in any therapeutic research study within the last 8 weeks. * Have participated in any other gene therapy study including patients who have received DTA-H19/PEI in the past.

NCT_ID NCT00595088

Study_NamePhase 2b, Trial of Intravesical DTA-H19/PEI in Patients With Intermediate-Risk Superficial Bladder Cancer

Study Objectives Rituximab is the first monoclonal antibody to receive approval in the treatment of cancer and has been proven to lead to extended survival when administered intravenously in the treatment of patients with systemic non-Hodgkin's lymphoma. We have previously demonstrated that a small fraction of Rituximab administered intravenously is able to cross the blood-brain-barrier into the brain. We will test the idea that the direct injection into the cerebrospinal fluid of Rituximab, a monoclonal antibody which attacks and kills lymphoma cells, is safe and when used in combination with methotrexate in patients with recurrent brain and intraocular lymphoma. We will also test the idea that the combination of rituximab plus methotrexate has activity and is effective in the treatment of recurrent brain and intraocular lymphoma. Conditions: Central Nervous System Lymphoma, Intraocular Lymphoma Intervention / Treatment: DRUG: Intraventricular Rituximab Plus MTX Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Relapsed, refractory CNS lymphoma, ocular lymphoma, lymphomatous meningitis * Tumors must be CD20 + on pathologic analysis. * Patients must have an Ommaya reservoir (ventricular access device. * Patients may have had prior intrathecal methotrexate, ara-C or thiotepa but must have recovered from any reversible toxicity caused by prior treatment. * Concurrent systemic chemotherapy is allowed for treatment of disease outside the meninges with the exception of high-dose methotrexate (>500 mg/m2/d, high-dose ara-C (> 2 gm/m2/d), high-dose thiotepa (>300 mg/m2/d) or investigational agents. * Patients must have sufficient baseline hematologic function: >1,500 granulocytes and >50,000 platelets/ul. * Patients must have had a nuclear medicine CSF flow study performed within 30 days of treatment which shows no significant obstruction within the ventricles. Exclusion Criteria: * History of whole brain or craniospinal irradiation or intrathecal chemotherapy < 4 days before initiation of intra-CSF administration of rituximab. * Anticipated survival of less than one month. * HIV infection. -

NCT_ID NCT00221325

Study_NameA Safety Study of Rituximab Plus MTX Injected Into the Cerebrospinal Fluid in the Treatment of Brain Lymphoma

Study Objectives The purpose of the safety run in Phase I portion of this study is to confirm the recommended Phase II dose of ipilimumab and nivolumab among participants treated with combined thoracic radiation therapy (30 Gy in 10 fractions) and nivolumab/ipilimumab following standard treatment with 4-6 cycles of platinum-based chemotherapy. The purpose of the Phase II portion of this study is to estimate the 6-month Progression Free Survival (PFS) rate among participants treated with ipilimumab and nivolumab with thoracic radiation therapy (30 Gy in 10 fractions) after standard treatment with 4 to 6 cycles of platinum based chemotherapy. Conditions: Small Cell Lung Cancer, Extensive-stage Small Cell Lung Cancer Intervention / Treatment: RADIATION: Thoracic Radiation Therapy, DRUG: Ipilimumab, DRUG: Nivolumab Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Signed Written Informed Consent * Willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study. * Patients with Small Cell Lung Cancer (SCLC) documented by histology or cytology from brushing, washing, or needle aspiration of a defined lesion, but not from sputum cytology alone * Have presented at initial diagnosis with extensive-stage disease * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1 * Have received 4 <= age <= 6 cycles of platinum-based first-line chemotherapy and have an ongoing response of complete response (CR), partial response (PR), or stable disease (SD) after completion of chemotherapy. Acceptable combinations, as recommended per National Comprehensive Cancer Network (NCCN) guidelines, include cisplatin or carboplatin combined with either etoposide or irinotecan; As an exception to the above criterion, participants receiving only 3 cycles of chemotherapy due to toxicity are eligible, if they have an ongoing PR or CR after the 3rd cycle; Participants who have received > 6 cycles of platinum-based first-line chemotherapy are not eligible. * Participants must initiate study treatment with thoracic radiation therapy less than or equal to 8 weeks (56 days) from the last dose of platinum-based first line chemotherapy. * Whenever possible, a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block or 10 unstained slides of tumor sample (archival or recent) for biomarker evaluation should be made available and submitted to the central lab for correlative studies. * Participant re-enrollment: This study permits the re-enrollment of a participant who has discontinued the study due to pre-treatment failure (i.e., participant has not been treated). If re-enrolled, the participant must be re-consented. * Men and women at least 18 years * Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to the start of thoracic radiation therapy * Women must not be breastfeeding. * WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of study drug (half-life up to 25 days) plus 30 days (duration of ovulatory cycle) for a total of 5 months post-treatment completion. * Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug (s) plus 5 half-lives of the study drug (half-life up to 25 days) plus 90 days (duration of sperm turnover) for a total of 7 months post-treatment completion. * Additional criteria may apply Exclusion Criteria: * Participants with previous brain metastases are eligible provided that they are treated and asymptomatic not requiring steroids or anticonvulsants, and have stable disease at the screening tumor assessment. A 4 week disease stable interval as confirmed by MRI or CT brain with contrast is required after treatment of brain metastases before initiation of thoracic radiation therapy. In addition, participants must have been either off corticosteroids, or on a stable or decreasing dose of 10 mg daily prednisone (or equivalent). * Participants who have received prior chest radiation which at the discretion of the treating radiation oncologist precludes delivery of protocol radiation therapy * Carcinomatous meningitis * Pleural effusion that cannot be controlled with appropriate interventions * All toxicities attributed to prior anti-cancer therapy must have been resolved to Grade 1 (NCI CTCAE Version 4) or baseline before administration of study drug(s) other than: Patients with toxicities attributed to prior anti-cancer therapy that either are not expected to resolve and/or result in long-lasting sequelae, such as neuropathy after platinum-based therapy, or are not expected to interfere with treatment on study, such as fatigue,alopecia, or grade 2 hematologic toxicity are eligible. * Women who are pregnant or breastfeeding * Active, known, or suspected autoimmune disease. Patients with an autoimmune paraneoplastic syndrome requiring concurrent immunosuppressive treatment are excluded. Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. * A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Corticosteroids with minimal systemic absorption (inhaled or topical steroids) and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease. * Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways) * Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity * Any patient requiring supplemental oxygen therapy * Previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period * Known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug(s) administration or interfere with the interpretation of safety results * Major surgery or significant traumatic injury that is not recovered at least 14 days before the initiation of thoracic radiation therapy. * Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBVsAg) test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection * Individuals with a positive test for HCV antibody but no detection of HCV RNA indicating no current infection are eligible * Known medical history of testing positive for human immunodeficiency virus (HIV) or known medical history of acquired immunodeficiency syndrome (AIDS) * Inadequate hematologic function according to study guidelines * Inadequate hepatic function according to study guidelines * History of allergy or hypersensitivity to any of the study drugs or study drug components * Additional criteria may apply

NCT_ID NCT03043599

Study_NameIpilimumab + Nivolumab w/Thoracic Radiotherapy for Extensive-Stage Small Cell Lung Cancer

Study Objectives RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of topical myristyl nicotinate cream may stop skin cancer from forming. PURPOSE: This randomized phase I trial is studying the side effects and best way to give topical myristyl nicotinate cream on the skin of healthy volunteers. Conditions: Healthy Intervention / Treatment: DRUG: Topical Myristyl Nicotinate Cream, DRUG: Placebo Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Subjects 18 years or older with normal skin * Have used no topical medications on the skin of the upper extremities, except for emollients or sunscreens, for at least 30 days prior to study entry * Agree to limit sun exposure as much as possible and wear protective clothing on the forearms in place of using sunscreens or moisturizers * Ability to understand and willingness to sign an informed consent before initiation of therapy after the nature of the study has been explained to them * Females must be surgically sterile by hysterectomy or post menopausal Exclusion Criteria: * Subjects with no signs of inflammation or irritation of the skin on the forearms * Subjects with prior history of actinic keratosis or skin cancer on the forearm * Females of child bearing potential * Subjects with any concurrent therapy (e.g., retinoids, fluorouracil) on the forearms that may interfere with clinical evaluations * Subjects taking oral supplemental niacin, by itself or in the form of a multi-vitamin that exceeds 40 mg/day * No known immunosuppression by virtue of medication or disease, including AIDS patients, subjects taking oral prednisone, and subjects on immunosuppressants/immunomodulators( cyclosporine, chemotherapeutic agents, or biologic therapy), determined by the examining investigator/co-investigator * Uncontrolled intercurrent illness including, but not limited to any of ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Subjects who have had invasive cancer within the past 5 years * Skin conditions felt by the study physician to contraindicate enrollment including, but not limited to, psoriasis or atopic dermatitis within a proposed treatment area * Less than 30 days since prior and no concurrent or planned participation in another clinical trial

NCT_ID NCT00619060

Study_NameTopical Myristyl Nicotinate Cream on the Skin of Healthy Volunteers

Study Objectives To determine the safety and efficacy of the combination of HDI and anti-CTLA-4 monoclonal antibody for patients with recurrent inoperable stage III or stage IV melanoma. Conditions: Melanoma Intervention / Treatment: DRUG: Anti-CTLA4 monoclonal antibody and HDI Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: OTHER Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must have a written informed consent obtained prior to the initiation of study procedures. * Male and female subjects greater than or equal to 18 years. * Patients must have histologically confirmed recurrent stage III or stage IV melanoma (AJCC 6th edition classification). Cutaneous melanoma, ocular or mucosal melanoma will be eligible. * Patients must have measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST). Baseline measurements must be obtained within 4 weeks prior to initiating therapy. * Patients must have adequate hematologic, renal, and liver function as evidenced by the following (within 4 weeks prior to starting the study drugs): * WBC greater than or equal to 3,000/mm3 * Lymphocytes greater than or equal to 1,000/mm3 * Platelets greater than or equal to 100,000/mm3 * Serum Creatinine less than or equal to 1.5 x upper limit of normal (ULN) * Serum Bilirubin less than or equal to 1.5 x ULN * Serum AST/ALT less than or equal to 2.5 x ULN * Serum LDH less than or equal to 2.0 x ULN * APTT less than < 40 s * Patients must have fully recovered from any effects of major surgery, and be free of significant detectable infection. * Patients must not have received any chemotherapy, hormonal therapy, radiotherapy, or biological therapy within the preceding 4 weeks. * Patients must not have previous therapy with Anti-CTLA4 monoclonal antibodies (including CP-675,206 and MDX-010). Previous therapy with Interferon-alfa 2b in the adjuvant or metastatic setting is allowed. Previous therapy with other biological agents (including vaccines and GM-CSF) is allowed. * Patients must have ECOG performance status of 0 or 1. * Patients must not have autoimmune disorders (except vitiligo). Patients with positive titers for autoimmune antibodies are allowed on the study in the absence of history of clinical manifestations of autoimmune disease. * Patients must not have conditions of immunosuppression or chronic requirement for treatment with systemic steroids, including oral steroids, continuous use of topical steroid creams or ointments, or any inhaled steroid containing inhalers. Patients who discontinue use of these classes of medication for at least 2 weeks are eligible. Treatment with steroids or other immunosuppressant medications is allowed during the study if clinically required to treat side effects related to autoimmunity that may develop secondary to the study agents. * Patients must be free of brain metastasis by contrast-enhanced CT/MRI scans within 4 weeks prior to starting the study drugs. If known to have prior brain metastases, must not have evidence of active brain disease on two successive MRI evaluations at least 3 months apart (one of which is £ 4 weeks prior to starting the study drugs). * Female patients of child bearing potential must have a negative pregnancy test, and must not be breast feeding. * Patients must agree to use effective contraception (both males and females). Exclusion Criteria * Serious illnesses, such as: cardiovascular disease (uncontrolled congestive heart failure, hypertension, cardiac ischemia, myocardial infarction, severe cardiac arrhythmia), bleeding disorders, autoimmune diseases, severe obstructive or restrictive pulmonary diseases, active systemic infections, and inflammatory bowel disorders. * Treatment with mitomycin C or nitrosureas within six weeks prior to study entry. * Any significant psychiatric disease, medical intervention, or other condition, which in the opinion of the principal investigator, could prevent adequate informed consent or compromise participation in the clinical trial. * Active infection or antibiotics within one-week prior to study, including unexplained fever (temp > 38.1°C). * Treatment with anticoagulants, except to keep an indwelling line patent. * Systemic steroid or other immunosuppressive therapy within 4 weeks of starting the study. * Treatment with any investigational product within 28 days of registration. * History of inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis), celiac disease, or other chronic gastrointestinal conditions associated with diarrhea, or current acute colitis of any origin, or any history of diverticulitis (even a single episode) or evidence of diverticulitis at baseline, including evidence limited to CT-scan only. * Patients who did not tolerate high-dose interferon-α therapy in the adjuvant setting will be excluded.

NCT_ID NCT00610857

Study_NameSafety and Efficacy of Combination HDI and Anti-CTLA4 for Recurrent Inoperable Stage III or Stage IV Melanoma

Study Objectives This research study is evaluating how a drug called lenalidomide, given in combination with the standard chemotherapy regimen of Mitoxantrone, Etoposide, and Cytarabine, commonly referred to as MEC, works in individuals with either relapsed or refractory AML Conditions: AML Intervention / Treatment: DRUG: Etoposide, DRUG: Cytarabine, DRUG: Lenalidomide, DRUG: Mitoxantrone Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Acute myelogenous leukemia diagnosed by WHO criteria with one of the following (patients with biphenotypic leukemia are eligible, provided that the treating physician determines an AML treatment regimen is appropriate) * Primary refractory disease following > 1cycle of chemotherapy, (such as hypomethylating agent or induction chemotherapy) * First relapse or higher. Patients with primary or secondary acute myelogenous leukemia are eligible. * Age 18 <= age <= 70 years * LVEF > 50 % * ECOG Performance status 0 <= age <= 2 * Able to adhere to study schedule and other protocol requirements. * Participants must have normal organ function as defined below, unless felt due to underlying disease and approved by the overall PI. Patients with Gilbert's disease may have total bilirubin up to < 3 x ULN. * Creatinine < 2.0mg/dl * Total bilirubin < 1.5 x ULN * AST (SGOT) and ALT (SGPT) < 3 x ULN. * Patients may receive hydroxyurea, steroids, or leukapheresis as necessary until Day 5 of treatment. * Patients must give voluntary written informed consent and HIPAA authorization before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. * Patients may have had prior treatment for MDS or AML, including prior lenalidomide for MDS or AML or another condition. * Patient may have had prior autologous or allogeneic transplant (family member, unrelated donor, or cord blood) if there is at least 90 days between transplant and study entry. * Patients may also have had donor lymphocyte infusion if there is at least 60 days between donor lymphocyte infusion and study entry. * Patients on immunosuppression are also eligible. * Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL prior to receiving treatment with lenalidomide, and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. * Ability to understand and the willingness to sign a written informed consent document. * All study participants must be registered into the mandatory Revlimid REMS ® program, and be willing and able to comply with the requirements of the REMs ® program. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program Exclusion Criteria: * Known hypersensitivity to thalidomide or lenalidomide (if applicable). * The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs. * Known seropositive for human immunodeficiency virus (HIV). HIV testing is not required. Hepatitis testing is not required. * Patients who have had a myocardial infarction within 6 months of enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. * Any serious medical condition laboratory abnormality or psychiatric illness that would prevent the subject from signing the consent form. * Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. * Patients with major surgery within 28 days prior to treatment. * Patients with any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol. * Patient has received an investigational agent or cytotoxic chemotherapy (excluding hydroxyurea) within 7 days of study entry. * Patients with acute promyelocytic leukemia. * Females who are pregnant

NCT_ID NCT03118466

Study_NameMitoxantrone, Etoposide, and Cytarabine (MEC) Plus Lenalidomide for Relapsed or Refractory Acute Myeloid Leukemia

Study Objectives This is a Phase IIIb, interventional, single arm, multicentre study to evaluate safety, effectivenees, use of resources and patient reporting outcomes in patients with ES-SCLC treated with durvalumab in combination with platinum-etoposide as first-line treatment in Spain. Conditions: Small Cell Lung Carcinoma Extensive Disease Intervention / Treatment: DRUG: Durvalumab, DRUG: Cisplatin, DRUG: Etoposide, DRUG: Carboplatin Location: Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically or cytologically documented Small cell Lung Cancer with extensive disease. * Patients who had received chemoradiotherapy for LS-SCLC and have experienced a treatment-free interval of at least 6 months since last chemotherapy, radiotherapy, or chemoradiotherapy cycle, can be included under investigator criteria. * Brain metastases; must be asymptomatic or have been treated at least 2 weeks prior to study treatment and are currently receiving 10 mg/day or less of prednisone or equivalent. * Patients must be considered suitable to receive a platinum-based chemotherapy regimen as 1st line treatment for ES-SCLC. * ECOG Performance Status of 0 <= age <= 2 at enrolment. * No prior exposure to immune-mediated therapy for cancer. * Adequate hematologic and organ function. * Life expectancy of at least 12 weeks. * Body weight >30 kg. Exclusion Criteria: * Any history of radiotherapy to the chest prior to systemic therapy or planned consolidation chest radiation therapy (except paliative care outside of the chest). * Paraneoplastic syndrome of autoimmune nature, requiring systemic treatment or clinical symptomatology suggesting worsening of PNS * Active infection including tuberculosis, HIV, hepatitis B anc C * Active or prior documented autoimmune or inflammatory disorders * Uncontrolled intercurrent illness, including but not limited to interstitial lung disease.

NCT_ID NCT04712903

Study_NameDurvalumab Plus Chemotherapy in Untreated Patients With Extensive-Stage Small Cell Lung Cancer

Study Objectives Phase 0 - Open label, Single dose study of siG12D LODER in Patients with operable adenocarcinoma of the pancreas. The primary endpoint: To assess efficacy and local distribution of siRNA out of eight high dose siG12D LODERs in patients diagnosed with operable adenocarcinoma of the pancreas. The Secondary endpoint: Short term tolerability and safety assessment Phase I - This study is designed to investigate the safety of siG12D LODER (Local Drug EluteR) in patients diagnosed with adenocarcinoma of the pancreas. The primary endpoint: To asses efficacy of siG12D LODER and local distribution in non-operable patients by histopathology measurements, local distribution by RNA analysis. To define the dose-limiting toxicities (DLT) The Secondary endpoint 1. To determine the recommended Phase II dose (RP2D) 2. To define and maximum tolerated dose (MTD) 3. In the event of surgery, assessment of siG12D LODER local distribution and efficacy will be based on histopathology measurements and RNA analysis. 4. Progression free survival - only by long term follow-up Conditions: Pancreatic Ductal Adenocarcinoma, Pancreatic Cancer Intervention / Treatment: DRUG: siG12D LODER Location: Israel Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: Phase 0: Provide written informed consent and be between the ages of 18 and up, inclusive. * Patient that is diagnosed as respectable locally pancreatic tumor * Have a target tumor accessible for intratumoral administration by EUS (Endoscopic Ultrasound) guidance as determined by the physician performing the EUS guided LODER insertion. * Have a Karnofsky performance status of >= 70%. * Have a life expectancy of >= 3 months. * If female and of child-bearing potential, have a negative serum pregnancy test during screening. * Agree to use of a barrier method of contraception if sexually active (both men and women) from the time of administration of the first treatment and for at least 8 weeks after treatment. * Have serum creatinine < 2.0 mg/dL, , PT, - INR < 1.5 absolute neutrophil count (ANC) > 1,000 x 103 cells/mL, platelets >= 75,000/mL, and hemoglobin >= 10 mg/dL. * Have screening procedures completed within 2 weeks of starting treatment. * No other malignancy present that would interfere with the current intervention. * Have measurable disease. Phase I * Provide written informed consent and be between the ages of 18 and up. * Have an unresectable, locally advanced diagnosed or highly suspected adenocarcinoma of the pancreas. Or patients with a tumor and are not planed to undergo surgery due to a high surgical risk (e.g. coagulopathy or severe congestive heart failure). * Allocated to receive standard of care chemo as first line treatment. * Have a target tumor that is accessible for intratumoral administration by PTA or EUS guidance as determined by the radiologist/gastroenterologist performing the PTA/EUS injection. * Have a Karnofsky performance status of >= 70%. * Have a life expectancy of >= 3 months. * If female and of child-bearing potential, have a negative serum pregnancy test during screening. * Agree to use of a barrier method of contraception if sexually active (both men and women) from the time of administration of the first treatment and for at least 8 weeks after treatment. * Have serum creatinine < 2.0 mg/dL, PT - INR < 1.5, absolute neutrophil count (ANC) > 1,000 x 103 cells/mL, platelets >= 75,000/mL, and hemoglobin >= 10 mg/dL. * Have screening procedures completed within 4 weeks of starting treatment. * No other malignancy present that would interfere with the current intervention. * Have measurable disease. Exclusion Criteria: Phase 0: * Have distant metastasis spread (such as liver or lung, or lymph nodes metastases), peritoneal spread or malignant sites. * Have clinically significant pancreatitis within 12 weeks of treatment. * If female, be breast feeding. * Have a medical condition contraindicated for both percutaneous- and endoscopic- guided delivery or any intercurrent medical illness or other medical condition that would in the judgment of the investigator compromise patient safety or the objectives of the study. * Have a history of bleeding coagulopathy. * Have participated in any therapeutic research study within the last 4 weeks. Phase I: * Have distant metastatic spread (such as liver, lung, or lymph nodes metastases), peritoneal spread or malignant sites. * Have clinically significant pancreatitis within 12 weeks of treatment. * If female, be breast feeding. * Have a medical condition contraindicated for both percutaneous- and endoscopic- guided delivery or any intercurrent medical illness or other medical condition that would in the judgment of the investigator compromise patient safety or the objectives of the study. * Have a history of bleeding coagulopathy. * Have participated in any therapeutic research study within the last 4 weeks.

NCT_ID NCT01188785

Study_NamePhase I - Escalating Dose Study of siG12D LODER (Local Drug EluteR) in Patients With Locally Advanced Adenocarcinoma of the Pancreas, and a Single Dose Study of siG12D LODER (Local Drug EluteR) in Patients With Non-operable Adenocarcinoma of the Pancreas

Study Objectives This is an open-label, multicenter, Phase Ib study to evaluate the safety and therapeutic activity of RO6874281 in combination with pembrolizumab. The study will consist of 3 parts: a safety run-in (Part I: Cohorts 1.1. and 1.2) and two expansion parts (Parts II and III). Part II will start once all participants in Cohort 1.1 have completed the observation period. Part III will start once all participants in Cohorts 1.1 and 1.2 have completed the observation period. Conditions: Metastatic Melanoma Intervention / Treatment: DRUG: RO6874281, DRUG: Pembrolizumab Location: United States, Spain, Australia, Belgium, Canada, Russian Federation, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed unresectable stage III or stage IV cutaneous or mucosal melanoma (AJCC v8.0). * Participants need to have known BRAF status. * CPI naïve melanoma population: Participants with unresectable stage III or stage IV cutaneous or mucosal melanoma who have not received prior treatment for advanced disease. BRAF mutation-positive patients are eligible without prior treatment or after failure of BRAF directed inhibitor therapy. * CPI experienced melanoma population: Participants with unresectable stage III or stage IV cutaneous melanoma. Participants must have progressed during or after treatment with anti PD-1 antibody therapy, either as monotherapy or in combination with other agent(s). * Participants should have adequate cardiovascular, hematological, liver, and renal function. * Participants with unilateral pleural effusion are eligible if they fulfill both of the following: NYHA Class 1; Forced expiratory volume 1 (FEV1) >70% and forced vital capacity (FVC) >70% of predicted value; participants with lung metastases should present with DLCO >60% of predicted value. Exclusion criteria: Medical Conditions * Rapid disease progression or suspected hyperprogression (as determined by the Investigator) or threat to vital organs or critical anatomical sites requiring urgent alternative medical intervention. * Known active CNS metastases and/or carcinomatous meningitis/leptomeningeal disease: Participants with previously treated brain metastases may participate. * History of treated asymptomatic CNS metastases. * An active second malignancy (exceptions are non-melanoma skin cancer, cervical carcinoma in situ, or prostate carcinoma that is in remission under androgen deprivation therapy for >= 2 years, or participants who have a history of malignancy and have been treated with curative intent and the participant is expected to be cured as per Investigator's assessment). * Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, and known autoimmune diseases or other disease with ongoing fibrosis (such as scleroderma, pulmonary fibrosis. and emphysema). * Episode of significant cardiovascular/cerebrovascular acute disease within 6 months before study treatment administration. * Active or uncontrolled infections, including latent tuberculosis. * Known HIV infection. * Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. * Severe infection within 4 weeks before study treatment administration, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia. * History of chronic liver disease or evidence of hepatic cirrhosis. * Dementia or altered mental status that would prohibit informed consent. * History of autoimmune disease. * Adverse events related to any previous radiotherapy, chemotherapy, targeted therapy, CPI therapy or surgical procedure that have not resolved to Grade =< 1, except alopecia (any grade) and Grade 2 peripheral neuropathy. * History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. * Bilateral pleural effusion. * Severe dyspnea at rest or requiring supplementary oxygen therapy. * Concurrent therapy with any other investigational drug (defined as a treatment for which there is currently no regulatory authority approved indication). * Immunomodulating agents: Last dose with any of the following agents, for example, etanercept, infliximab, tacrolimus, cyclosporine, mycophenolic acid, alefacept, or efalizumab (or similar agents) < 28 days before study treatment administration. Regular immunosuppressive therapy (i.e., for organ transplantation, chronic rheumatologic disease) * Treatment with systemic immunosuppressive medications including, but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents within 2 weeks prior to Cycle 1 Day 1. * Radiotherapy within the last 4 weeks before start of study treatment administration, with the exception of limited field palliative radiotherapy. * Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1. * Major surgery or significant traumatic injury < 28 days before study treatment administration (excluding fine needle biopsies) or anticipation of the need for major surgery during study treatment. * Known hypersensitivity to any of the components of the RO6874281 drug product or pembrolizumab drug product, including but not limited to hypersensitivity to Chinese Hamster Ovary cell products or other recombinant human or humanized antibodies. * No prior cytotoxic therapy for unresectable stage III or stage IV disease is permitted. * Toxicity from prior anti-PD-1 antibody therapy (including adjuvant treatment).

NCT_ID NCT03875079

Study_NameA Study To Evaluate Safety And Therapeutic Activity Of RO6874281 In Combination With Pembrolizumab, In Participants With Advanced Or Metastatic Melanoma

Study Objectives Investigators hypothesized that propofol dose for pituitary somatotroph patients might differ from nonfunctioning pituitary tumor, and investigators will evaluate a target controlled infusion (TCI) effect site concentration (Ce) of propofol for BIS score of 40 and LOC (loss of consciousness) in pituitary somatotroph patients in comparison with non functioning pituitary tumor patients. On arrival in the operating room, standard monitoring devices, including electrocardiogram, pulse oximetry, noninvasive blood pressure cuff, and bispectral index (BIS) will be applied to the patients. Propofol with the modified Marsh pharmacokinetic parameters using a keo of 1.2/min will be administered through TCI pump (OrchestraBase Primea, Fresenius Vial, France). The initial target Ce of propofol will be chosen as 3.0 mg/mL (0.5 mg/mL of incremental size) based on an earlier study. The sedation of patients will be assessed with BIS score and the modified observer's assessment of awareness and sedation (OAA/S). LOC was defined as an OAA/S lower than 2 (loss of response to spoken command to eye opening and loss of response to mild prodding or shaking). The primary end point of this study is the Ce of propofol when the BIS score is 40. The secondary end point of this study is the Ce of propofol at LOC. Conditions: Pituitary Tumor Intervention / Treatment: PROCEDURE: Not applicable (measuring subject's effect site concentration of propofol during the induction of general anesthesia) Location: Korea, Republic of Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * patients with pituitary somatotroph tumor and with nonfunctioning pituitary tumor in transsphenoidal pituitary surgery * American society of anesthesiologists classification 1 or 2 Exclusion Criteria: * left ventricle ejection fraction < 55% 3RD degree AV block, 2nd degree AV block with P:QRS > 3:1 * serum Creatinine > 1.0mg/dl * myocardial infarction or cerebral stroke in 1 yrs * fever > 38C * dementia, cognitive disorder, confused mental status * pregnant patients * allergic to propofol * illiteracy or foreigners

NCT_ID NCT03465423

Study_NameComparison of Propofol Requirement Between Patients With Pituitary Somatotroph Tumor and With Nonfunctioning Pituitary Tumor in Transsphenoidal Pituitary Surgery Under Total Intravenous Anesthesia

Study Objectives This phase II trial is studying the side effects and best dose of bortezomib and to see how well it works when given together with combination chemotherapy in treating younger patients with recurrent, refractory, or secondary acute myeloid leukemia (AML). Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as idarubicin, cytarabine, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with bortezomib may kill more cancer cells Conditions: Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1), Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myelomonocytic Leukemia (M4), Childhood Acute Basophilic Leukemia, Childhood Acute Eosinophilic Leukemia, Childhood Acute Erythroleukemia (M6), Childhood Acute Megakaryocytic Leukemia (M7), Childhood Acute Minimally Differentiated Myeloid Leukemia (M0), Childhood Acute Monoblastic Leukemia (M5a), Childhood Acute Monocytic Leukemia (M5b), Childhood Acute Myeloblastic Leukemia With Maturation (M2), Childhood Acute Myeloblastic Leukemia Without Maturation (M1), Childhood Acute Myelomonocytic Leukemia (M4), Recurrent Adult Acute Myeloid Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia Intervention / Treatment: DRUG: idarubicin, DRUG: cytarabine, DRUG: bortezomib, DRUG: etoposide, OTHER: laboratory biomarker analysis Location: Canada, United States, Australia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Diagnosis of acute myeloid leukemia (AML) according to WHO classification * At least 5% blasts in the bone marrow * With or without extramedullary disease * To be eligible for the dose-finding phase (closed as of 10/10) : * Relapsed patients must meet the following criteria: * Must have had a prior diagnosis of AML, but may NOT have inv(16) or t(8;21) cytogenetics * May be in first or any subsequent relapse * If in first relapse, remission duration must be less than one year * Refractory patients must meet the following criteria: * Must have had a prior diagnosis of AML * May have received one or more attempt at remission induction * Patients with treatment-related AML may be previously treated or untreated for secondary AML * To be eligible for the efficacy phase: * Relapsed patients must meet the following criteria: * Must have had a prior diagnosis of AML, with no restriction on prior cytogenetics * Must be in first relapse * Must not have received prior reinduction therapy * Refractory patients must meet the following criteria: * Must have had a prior diagnosis of AML * Must not have received more than one attempt at remission induction (which may consist of up to two therapy courses) * Patients with treatment-related AML must be previously untreated for secondary AML * No juvenile myelomonocytic leukemia or acute promyelocytic leukemia (APL; FAB M3) * Patients with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy: * CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs * CNS 2, defined as presence of < 5/μL WBCs in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm: * CNS 2a: < 10/μL RBCs; < 5/μL WBCs and cytospin positive for blasts * CNS 2b: >= 10/μL RBCs; < 5/μL WBCs and cytospin positive for blasts * CNS 2c: >= 10/μL RBCs; >= 5/μL WBCs and cytospin positive for blasts but negative by Steinherz/Bleyer algorithm * Patients with CNS3 disease (presence of >= 5/μL WBCs in CSF and cytospin positive for blasts [in the absence of a traumatic lumbar puncture] and/or clinical signs of CNS leukemia) are not eligible * CNS toxicity <= grade 2 * Lansky (patients <= 16 years) or Karnofsky (patients > 16 years) performance status (PS) 50 <= age <= 100% * ECOG PS 0 <= age <= 2 * No Down syndrome * No Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndrome * No evidence of active graft-vs-host disease * Creatinine clearance or radioisotope glomerular filtration rate >= 70 mL/min OR serum creatinine based on age/gender as follows: * 0.4 mg/dL for patients 1 month to < 6 months of age * 0.5 mg/dL for patients 6 months to < 1 year of age * 0.6 mg/dL for patients 1 to < 2 years * 0.8 mg/dL for patients 2 to < 6 years * 1 mg/dL for patients 6 to < 10 years * 1.2 mg/dL for patients 10 to < 13 years * 1.5 mg/dL (male) or 1.4 mg/dL (female) for patients 13 to < 16 years * 1.7 mg/dL (male) or 1.4 mg/dL (female) for patients >= 16 years * Total bilirubin <= 1.5 times upper limit of normal (ULN) for age * ALT < 3.0 times ULN for age (unless elevation due to leukemia involvement) * Shortening fraction >= 27% by ECHO OR LVEF >= 50% by gated radionuclide * Normal respiratory rate and pulse oximetry > 94% on room air * FEV_1 >= 80% of predicted * FVC and DLCO > 50% (corrected for hemoglobin) * Patients who are unable to perform pulmonary function tests (PFTs) (e.g., because of young age) will be excluded provided they have a medical history of significant prior pulmonary events or chronic pulmonary disease (e.g., pneumonia requiring mechanical ventilation support, pulmonary GVHD, pneumonectomy, or pulmonary toxin exposure) * Children with histories of resolved bronchiolitis, resolved viral pneumonias and well-controlled asthma are eligible, even if they are unable to perform PFTs * Patients with seizure disorder may be enrolled if on a non-enzyme-inducing anticonvulsant and if seizures are well-controlled * No uncontrolled infection * No known allergy to idarubicin, cytarabine, etoposide, boron, mannitol or bortezomib * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Concurrent radiotherapy allowed for patients who present with a chloroma that is producing or threatens to produce an irreversible neurologic deficit * Recovered from all prior chemotherapy, immunotherapy, or radiotherapy * More than 2 weeks since prior cytotoxic chemotherapy (4 weeks for nitrosoureas), except for hydroxyurea, which is allowed up to 24 hours prior to first dose of study drug, and intrathecal chemotherapy, which is allowed immediately up to administration of study drug * Prior steroid allowed as clinically indicated for patients with asthma * Hydrocortisone and methylprednisolone allowed as premedication in patients with a history of severe allergic reactions * At least 7 days since prior biologic agents, such as steroids, retinoids, or donor lymphocyte infusion without conditioning * At least 2 weeks since prior local palliative radiotherapy (small port) * At least 8 weeks since prior craniospinal radiotherapy or >= 50% radiation of pelvis * At least 6 weeks since prior other bone marrow radiation * At least 1 day since prior green tea containing products, any products containing vitamin C, flavanoids or other antioxidants (e.g., vitamins, herbal supplements), and foods with high vitamin C content * No prior radiotherapy to > 25% of lung volume * No prior total-body irradiation as part of a hematopoietic stem cell conditioning regimen * At least 2 months since prior stem cell transplantation * No concurrent graft-vs-host disease prophylactic medication * No prior bortezomib or other proteasome inhibitors * No other concurrent investigational drugs * More than 4 days since prior growth factors that support platelet or white cell number or function * No concurrent enzyme-inducing anticonvulsant medications known to be potent inducers of the cytochrome P450 system, including phenytoin, carbamazepine, and phenobarbital * Concurrent benzodiazepines and gabapentin allowed * No concurrent grapefruit juice with bortezomib * No other concurrent cancer chemotherapy or immunomodulating agents * No concurrent corticosteroids as anti-emetic therapy * Concurrent corticosteroids therapy allowed as treatment or prophylaxis for anaphylactic reactions, symptoms of cytarabine syndrome, and as treatment for presumptive bortezomib-induced pulmonary toxicity.

NCT_ID NCT00666588

Study_NameBortezomib and Combination Chemotherapy in Treating Younger Patients With Recurrent, Refractory, or Secondary Acute Myeloid Leukemia

Study Objectives The purpose of this study is to find out the good and bad effects that occur when temsirolimus is added to standard chemotherapy with carboplatin and paclitaxel. Conditions: Squamous Cell Cancer, Head and Neck Cancer Intervention / Treatment: DRUG: Temsirolimus + Weekly Paclitaxel + Carboplatin Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must have microscopically confirmed head and neck squamous cell carcinoma (HNSCC), recurrent and/or metastatic. * Confirmation of HNSCC may be obtained from the primary site or metastatic disease. * Patients must be at least 18 years. * Karnofsky Performance status must be >= 70%. * Disease must be measurable by RECIST criteria. * At least 6 weeks must have elapsed from previous radiation therapy. Patient must have recovered from the acute toxic effects of treatment prior to study enrollment. * Adequate organ function, as follows: * Adequate bone marrow reserve: absolute neutrophil count (ANC) >= 1.5 X 109/L, platelets >= 100 X 109/L, and hemoglobin >= 9 g/dL. * Hepatic: total bilirubin within normal limits (<= 1.0 mg/dL); alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) <= 1.5 X ULN (upper limit of normal) * Renal: Serum creatinine <= 1.3 mg/dL. Patients with serum creatinine > 1.3 mg/dL may be eligible if creatinine clearance (CrCl) >= 45 mL/min based on the standard Cockroft and Gault formula. * Patients of childbearing potential must have a negative serum pregnancy test within 14 days of treatment. Patients must agree to use a reliable method of birth control during and for 3 months following the last dose of study drug. * Patients must sign an informed consent document. Exclusion Criteria: * Previous exposure to temsirolimus or other mTOR inhibitors * More than 2 prior cytotoxic regimens in the recurrent/metastatic disease setting * History of any brain metastases * Patients who require concomitant medications that are metabolized by hepatic CYP3A4, due to potential drug-drug interaction with temsirolimus * Patients with known active interstitial pneumonitis * Active infection or serious underlying medical condition that would impair the patient's ability to receive protocol treatment. * Women who are pregnant or lactating * Other active malignancy, other than indolent malignancies which the investigator determines are unlikely to interfere with treatment and safety analysis * Diagnosis of Nasopharyngeal cancer is excluded. * Patients with multifocal peripheral sensory alterations or paresthesias (including tingling) interfering with function, per patient report (example: activities of daily living) * Therapeutic anticoagulation with Coumadin (warfarin) * Hypertriglyceridemia >= grade 2 (CTCAE version 3.0). * Impaired lung function: O2 saturation 88% or less at rest on room air by Pulse Oximetry. If O2 saturation is <= 88% at rest, further pulmonary function tests (PFTs) should be ordered to confirm normal pulmonary function and eligibility.

NCT_ID NCT01016769

Study_NameTemsirolimus + Weekly Paclitaxel + Carboplatin for Recurrent or Metastatic Head and Neck Squamous Cell Cancer (HNSCC)

Study Objectives The study will provide information on outcomes in people with multiple myeloma, or systemic AL amyloidosis, or both, under standard care. AL is short for amyloid light-chain. Standard care means the participant will be treated according to their clinic's standard practice. The study sponsor will not be involved in how participants are treated but will provide instructions on how the clinics will record what happens during the study. The aim of the study is to learn if treatment duration makes a difference in how participants with multiple myeloma or systemic AL amyloidosis respond to their treatment. During the study, participants will be treated according to their clinic's standard practice. Participants must have started their treatment up to 12 months before taking part in this study. During the study, the participants will visit their clinic every 3 months. These are extra visits to their clinic's standard visits. Conditions: Multiple Myeloma, Immunoglobulin Light-chain Amyloidosis Location: Spain Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Diagnosis of MM and/or AL amyloidosis according to the IMWG for MM and BSH guidelines for AL amyloidosis. MM diagnostic criteria: * Smouldering MM- Both criteria must be met: 1. Serum M protein (Immunoglobulin G [IgG] or IgA greater than or equal to (>=) 30 gram per liter (g/L) or urinary monoclonal protein (M protein) >= 500 milligram per 24 hours (mg/24 h) and/or clonal bone marrow (BM) plasma cells (PCs) 1 percent (%) - 60%. 2. Absence of myeloma-defining events or amyloidosis. * Multiple myeloma- Clonal BM plasma cells >= 10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following myeloma-defining events: 1. Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically: * Hypercalcemia: serum calcium greater than (>) 0.25 millimole per liter (mmol/L) (> 1 milligram per deciliter [mg/dL]) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL). * Renal insufficiency: creatinine clearance (CrCl) less than (<) 40 milliliter per minute (mL/min) or serum creatinine >177 micromole/liter (mcmol/L) (>2 mg/dL). * Anemia: haemoglobin (Hb) value of >20 g/L below the lower limit of normal or a Hb value of <100 g/L. * Bone lesions: one or more osteolytic lesions on skeletal radiography, computed tomography (CT) or positron emission tomography-computed tomography (PET-CT). 2. Any one or more of the following biomarkers of malignancy: * >=60% clonal BM plasma cells. * Involved/uninvolved serum-free light chain ratio >=100. * >1 focal lesions on magnetic resonance imaging (MRI) studies (each focal lesion must be >=5 millimeter (mm) in size). AL amyloidosis diagnosis: * In suspected AL amyloidosis, a histological diagnosis is essential and, where possible, a biopsy should be taken from an apparently affected organ. Alternatively, a subcutaneous abdominal fat aspirate and bone marrow biopsy may be examined for amyloid. * Congo red staining with classical apple green birefringence under polarized light should be used to test for the presence of amyloid on any histological specimen. * The diagnosis of amyloid requires an experienced laboratory as false negative and false positive diagnoses on the basis of histology are not infrequent. Other (non-AL) amyloid fibril types should be excluded by using immunohistochemistry, deoxyribonucleic acid (DNA) analysis, protein sequencing or mass spectrometry. * Under treatment for MM or systemic AL amyloidosis at the time of study entry. * Have started treatment up to 12 months before inclusion for MM or systemic AL amyloidosis, irrespective of the treatment regimen. * Having first, second, third or fourth line of treatment for MM or systemic AL amyloidosis, irrespective of the treatment regimen. * In case of participants with Newly Diagnosed Multiple Myeloma (NDMM) who are candidates to autologous stem cell transplant (ASCT), the ASCT has to be performed before study entry. Exclusion Criteria: * Participants with planned cessation of treatment for MM or systemic AL amyloidosis from participation to the study (example, due to pregnancy). * Participating in blinded clinical trials, or in clinical trials with no possibility of obtaining information required in this study, or in clinical trials in which participation in other studies is not allowed.

NCT_ID NCT04659798

Study_NameA Study to Investigate the Relationship Between Duration of Treatment and Response in Patients With Multiple Myeloma (MM) or Systemic AL Amyloidosis Treated in Real-life Practice

Study Objectives The purpose of this study is to determine whether the cancer vaccine tecemotide (L-BLP25) in addition to best supportive care is effective in prolonging the lives of subjects with unresectable stage III non-small cell lung cancer, compared to best supportive care alone. A local ancillary (sub) study in European centers will evaluate the immune response in peripheral blood after tecemotide (L-BLP25) or placebo vaccination. Conditions: Non-small Cell Lung Cancer Intervention / Treatment: BIOLOGICAL: Tecemotide (L-BLP25), DRUG: Single low dose cyclophosphamide, DRUG: Placebo Location: Poland, United Kingdom, Australia, Austria, Denmark, France, Korea, Republic of, India, Singapore, Netherlands, Greece, Canada, China, Slovakia, Portugal, Germany, Sweden, Spain, Czech Republic, Italy, Taiwan, Romania, Switzerland, Hong Kong, Argentina, Israel, United States, Brazil, Ireland, Belgium, Russian Federation, Mexico, Hungary Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Histologically or cytologically documented unresectable stage III non-small cell lung cancer (NSCLC) * Documented stable disease or objective response, according to Response Evaluation Criteria in Solid Tumors (RECIST), after primary chemoradiotherapy (either sequential or concomitant) for unresectable stage III disease, within 4 weeks (28 days) prior to randomization * Receipt of concomitant or sequential chemoradiotherapy, consisting of a minimum of two cycles of platinum-based chemotherapy and a minimum radiation dose of >=50 Gray (Gy). Subjects must have completed the primary thoracic chemo-radiotherapy at least four weeks (28 days) and no later than 12 weeks (84 days) prior to randomization. Subjects who received prophylactic brain irradiation as part of primary chemo-radiotherapy are eligible * Geographically accessible for ongoing follow-up, and committed to comply with the designated visits * An Eastern Cooperative Oncology Group (ECOG) performance status of 0 <= age <= 1 * A platelet count > 140 x 10^9/Liter; white blood cells (WBC) > 2.5 x 10^9/Liter and hemoglobin > 90 gram per liter (g/L) Exclusion Criteria: Pre-Therapies: * Undergone lung cancer specific therapy (including surgery) other than primary chemo-radiotherapy * Receipt of immunotherapy (e.g. interferons, tumor necrosis factor [TNF], interleukins, or biological response modifiers [granulocyte macrophage colony stimulating factor {GM-CSF}, granulocyte colony stimulating factor {G-CSF}, macrophage-colony stimulating factor {M-CSF}], monoclonal antibodies) within 4 weeks (28 days) prior to randomization * Receipt of investigational systemic drugs (including off-label use of approved products) within 4 weeks (28 days) prior to randomization Disease Status: * Metastatic disease * Malignant pleural effusion at initial diagnosis and/or at study entry * Past or current history of neoplasm other than lung carcinoma, except for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix or other cancer curatively treated and with no evidence of disease for at least 5 years * Autoimmune disease * A recognized immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; subjects who have hereditary or congenital immunodeficiencies * Any preexisting medical condition requiring chronic steroid or immunosuppressive therapy (steroids for the treatment of radiation pneumonitis are allowed) * Known Hepatitis B and/or C Physiological Functions: * Clinically significant hepatic dysfunction * Clinically significant renal dysfunction * Clinically significant cardiac disease * Splenectomy * Infectious process that in the opinion of the investigator could compromise the subject's ability to mount an immune response Standard Safety: * Pregnant or breast-feeding women, women of childbearing potential, unless using effective contraception as determined by the investigator * Known drug abuse/alcohol abuse * Legal incapacity or limited legal capacity

NCT_ID NCT00409188

Study_NameCancer Vaccine Study for Unresectable Stage III Non-small Cell Lung Cancer (START)

Study Objectives The aim of this double-blinded prospective randomised trial is to explore the potential benefits of early postoperative administration of Synbiotics (combination of prebiotics and probiotics) to patients who have undergone colectomy for cancer. The patients are randomised to either synbiotics or placebo administration at the day they are able to tolerate po liquid diet and for 15 days thereafter. Primary end points of the study will be: Assessment of gastrointestinal function-related quality of life at 1, 3 and 6 months postoperatively by the use of the validated questionnaire GIQLI (Gastrointestinal Quality of Life Index) Secondary end points will be: -Assessment of functional bowel disorders (diarrhea, constipation, etc) at 1, 3 and 6 months postoperatively based on the respective domains of the validated instrument EORTC QLQ-C30 Conditions: Colorectal Neoplasms Intervention / Treatment: DIETARY_SUPPLEMENT: Synbiotics, DIETARY_SUPPLEMENT: Placebo Location: Greece Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: SINGLE_GROUP Masking: QUADRUPLE

Inclusion Criteria: * Colectomy for histologically proven colorectal adenocarcinoma Exclusion Criteria: * Pregnancy, * hereditary cancer, * history of inflammatory bowel disease, * metastatic disease at presentation, * emergency operation, * major postoperative complications

NCT_ID NCT01479907

Study_NameSynbiotics and Gastrointestinal Function Related Quality of Life After Colectomy for Cancer

Study Objectives This study is to examine which dose of DA-3031(PEG-G-CSF) has similar efficacy and safety compared to daily G-CSF in chemotherapy-induced neutropenia. Conditions: Chemotherapy Induced Neutropenia Intervention / Treatment: DRUG: PEG-G-CSF, DRUG: G-CSF Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Diagnosis of stage II or III breast cancer * Age : >=18, <=70 * TAC regimen as adjuvant therapy * ANC>=1,500/mm3, Platelet>=100,000/mm3, ECOG : 0 or 1 * Creatinine < 1.5 x ULN * Total bilirubin/AST/ALT < 1.5 x ULN, ALP < 2.5 x ULN * Have given a written, informed consent Exclusion Criteria: * Received any other investigational drugs within 30 days of informed consent date * Received systemic antibiotics within 72 hours of chemotherapy into this study or Radiation therapy within 4 weeks of informed consent date * Infective symptom before chemotherapy into this study * Pregnant or lactating women * Prior bone marrow or stem cell transplantation * Other malignancy history within 5 years * HIV positive * Prior exposure to pegfilgrastim or filgrastim or other colony-stimulating factors within 6 weeks of informed consent date * Prior chemotherapy

NCT_ID NCT01923545

Study_NamePhase II Study of DA-3031(PEG-G-CSF) in Chemotherapy-induced Neutropenia

Study Objectives The study was designed to investigate the optimal management of hyperglycemia developed during pasireotide treatment in participants with Cushing's disease or Acromegaly, which was not manageable with metformin. This was a Phase IV, multi-center, randomized, open-label study. Eligible patients started pasireotide subcutaneously (s.c.) for Cushing's disease and pasireotide LAR (long-acting release) for Acromegaly. Participants being treated with pasireotide s.c or LAR at screening were eligible as long as they met protocol criteria during the screening period. If previously normo-glycemic participants experienced an increase in their fasting blood glucose and met the criteria for diabetes while on pasireotide, they started anti-diabetic treatment using metformin. If they continued to have elevated blood glucose above target on metformin within the first 16 weeks, they were randomized in a 1:1 ratio to receive treatment with incretin based therapy or insulin for approximately 16 weeks. Participants who continued to receive clinical benefit after completing the Core Phase could enter an optional Extension Phase if pasireotide was not commercially available in their country or a local access program was not available to provide drug. Patients continued in the Extension Phase until the last participant randomized in the Core Phase completed 16 weeks of treatment post-randomization. Conditions: Cushing's Disease, Acromegaly Intervention / Treatment: DRUG: Pasireotide s.c., DRUG: Sitagliptin, DRUG: Liraglutide, DRUG: Insulin, DRUG: Pasireotide LAR, DRUG: Metformin Location: Peru, Poland, Germany, Thailand, United States, Brazil, Belgium, Denmark, Russian Federation, Turkey, China, India Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patients greater than or equal to 18 years * Confirmed diagnosis of Cushing's disease or acromegaly Exclusion Criteria: * Patients who require surgical intervention * Patients receiving DPP-4 inhibitors or GLP-1 receptor agonists within 4 weeks prior to study entry * HbA1c > 10 % at screening * Known hypersensitivity to somatostatin analogues Other protocol-defined inclusion/exclusion criteria may apply.

NCT_ID NCT02060383

Study_NameStudy of Management of Pasireotide-induced Hyperglycemia in Adult Patients With Cushing's Disease or Acromegaly

Study Objectives The purpose of this study is to determine whether CPC634 (CriPec® docetaxel) is effective in the treatment of patients with advanced epithelial ovarian cancer who are resistant to prior platinum-based chemotherapy . Conditions: Cancer, Ovarian Cancer Intervention / Treatment: DRUG: CPC634 (CriPec® docetaxel) Location: Belgium, Netherlands, United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Age 8 years. * Histologically or cytologically confirmed diagnosis of epithelial ovarian, fallopian or peritoneal cancer. * Platinum-resistant recurrent epithelial ovarian cancer (defined as progression within 6 months after last platinum dose). Subjects who have received a maximum of 2 prior treatment lines of which one could have been taxane- based. * Measurable disease according to RECIST version 1.1. Only CA-125 progression without any clinical or radiological progression is not allowed. * Performance status (WHO scale/ECOG) 1. * Estimated life expectancy of at least 5 months. * Toxicities incurred as a result of previous anti-cancer therapy (radiation therapy, chemotherapy, or surgery) must be resolved to <= Grade 2 (as defined by NCI- CTCAE version 5.0). * ANC >= 1.5 x 109/L; platelets >=100 x 109/L; hemoglobin >= 5.58 mmol/L (>= 9.00 g/dL) * Creatinine <= 1.75 x Upper Limit of Normal (ULN) and estimated creatinine clearance >= 30 mL/min according to Cockcroft-Gault formula; Serum albumin levels > 25g/L. * Serum bilirubin <= 1.5 x ULN except for subjects with Will Gilbert's syndrome; alkaline phosphatase, ASAT and ALAT <= 2.5 x ULN, unless related to liver metastases, in which case <= 5 x ULN is allowed. * Written informed consent according to local guidelines. Exclusion Criteria: * Subjects with platinum-refractory disease. Refractory disease is defined by subjects who progressed during the preceding treatment or within 4 weeks after last dose of platinum containing therapy. * Less than four weeks since the last treatment with other anti-cancer therapies, (i.e. endocrine therapy, immunotherapy, radiotherapy, chemotherapy, etc.); less than eight weeks for cranial radiotherapy, and less than six weeks for nitrosoureas and mitomycin C prior to first study treatment. * Current or recent (within 28 days of first study treatment) treatment with another investigational drug or participation in another investigational study. * Active or symptomatic brain metastases. Subjects must be on a stable or decreasing dose of corticosteroids and/or have no requirement for anticonvulsants for five days prior to Cycle 1 day1 (C1D1). * Current malignancies other than epithelial ovarian, fallopian or peritoneal cancer, with exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. * Major surgical procedure (including open biopsy, excluding central line IV and portacath) within 28 days prior to the first study treatment, or anticipation of the need for major surgery during the course of the study treatment. * Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100mm Hg). * Grade >= 2 motor or sensory neuropathy symptoms (as defined by CTCAE version 5.0). * Known hypersensitivity to any of the study drugs or excipients or taxanes. * Any skin toxicity in the medical history of the subject of Grade >= 2 associated with impaired skin integrity (skin toxicity defined as any form of rash, HFS, skin ulceration, toxic epidermal necrolysis, eczema) or any skin toxicity for which systemic treatment was needed. * Clinically significant (i.e. active) cardiovascular disease defined as stroke, transient ischemic attack (TIA) or myocardial infarction within <= 6 months prior to first trial treatment. * Subjects, who are pregnant or breastfeeding. Serum pregnancy test to be performed within 7 days prior to study treatment start in subjects of childbearing potential. * Absence of highly effective method of contraception as of C1D1 in female subjects of childbearing potential (defined as < 2 years after last menstruation and not surgically sterile). * Known hypersensitivity to dexamethasone or any other reason that would make the subject not eligible to receive dexamethasone. * Evidence of any other medical conditions (such as psychiatric illness, infectious diseases, drug or alcohol abuse, physical examination or laboratory findings) that may interfere with the planned treatment, affect subject compliance or place the subject at high risk from treatment- related complications.

NCT_ID NCT03742713

Study_NameEfficacy Study of CPC634 (CriPec® Docetaxel) in Platinum Resistant Ovarian Cancer

Study Objectives Primary: To evaluate if progression-free survival from first treatment to progression or death during second-line therapy (total PFS) of sorafenib followed by sunitinib is superior compared to sunitinib followed by sorafenib. Secondary: 1. Time from first treatment to progression during second-line therapy (total TTP) 2. Time to first-line treatment failure (progression, death, discontinuation due to toxicity) descriptively in each arm 3. PFS in first-line and second-line treatment, descriptively 4. Overall survival, descriptively (data cut-off same as for primary endpoint) 5. Disease Control Rate (DCR); Response rates in first-line and in second-line (CR, PR, SD according to RECIST criteria) 6. Cardiotoxicity analysis by means of echocardiography and NT-pro BNP with an interim analysis after 100 patients of each arm have completed the study 7. Safety and tolerability Conditions: Renal Cell Carcinoma Intervention / Treatment: DRUG: Sunitinib (Sutent), DRUG: Sorafenib (Nexavar) Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patients with metastatic / advanced RCC (all histologies), who are not suitable for cytokine therapy and for whom study medication constitutes first-line therapy * Age >= 18 ans <= 85years * ECOG Performance Status of 0 or 1 * MSKCC prognostic score, low or intermediate * Life expectancy of at least 12 weeks. * Subjects with at least one uni-dimensional (for RECIST) measurable lesion. Lesions must be measured by CT/MRI-scan. * Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of therapy: * Hemoglobin >= 9.0 g/dl * Absolute neutrophil count (ANC) >= 1,500/mm³ * Platelet count >= 100,000/μl * Total bilirubin <= 1.5 times the upper limit of normal * ALT and AST <= 2.5 x upper limit of normal (<= 5 x upper limit of normal for patients with liver involvement of their cancer) * Alkaline phosphatase < 4 x upper limit of normal * PT-INR/PT < 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.] * Serum creatinine <= 2 x upper limit of normal. * Written Informed Consent Exclusion Criteria: * History of cardiac disease: congestive heart failure >NYHA class 2 or with LVEF at baseline echocardiography < 50%; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension (defined as blood pressure >= 160 mmHg systolic and/or >= 90 mmHG diastolic on medication). * History of HIV infection or chronic hepatitis B or C * Active clinically serious infections (> grade 2 NCI-CTC version 3.0) * Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry) * Patients with seizure disorder requiring medication (such as steroids or anti-epileptics) * History of organ allograft * Patients with evidence or history of bleeding diathesis * untreated hypothyrosis * Patients undergoing renal dialysis * Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry. * Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 3 months after the completion of trial. * Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results * Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study * Patients unable to swallow oral medications * Known allergy to sunitinib or sorafenib or one of its constituents Excluded therapies and medications, previous and concomitant: * Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry. * Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed). Major surgery within 4 weeks of start of study * Autologous bone marrow transplant or stem cell rescue within 4 months of study * Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator; however they may not be substituted for a required dose reduction.] [Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study] * Investigational drug therapy outside of this trial during or within 4 weeks of study entry * Prior exposure to the study drug. * Any St. John's wort containing remedy

NCT_ID NCT00732914

Study_NameSequential Study to Treat Renal Cell Carcinoma

Study Objectives PACT is a non-randomized multicentre phase I/II study to evaluate the feasibility and safety of the prophylactic administration of donor derived TCM. Patients with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) who are planned to undergo a HLA -matched (9/10 or 10/10) allogeneic hematopoietic stem cell transplantation and who are either 50+ years old or have a high comorbidity score are included according to criteria as described below. TCM will be applied in escalating doses to a maximum of 30 patients who have received T cell depleted Human leukocyte antigen (HLA)-matched alloHSCT grafts and qualify for TCM transfer. Conditions: Leukemia, Myeloid, Acute, Myelodysplastic Syndromes Intervention / Treatment: BIOLOGICAL: TCM allogeneic humane central memory T cells, cryopreserved Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: Patient * Male or female patients with Hematopoietic Cell Transplant-Co-morbidity Index (HCT-CI) score (Sorror) >=3 AND/or Age >= 50 years * Primary or secondary AML Month 0, Month 1, Month 2, Month 4, Month 5, Month 6 and Month 7, in Complete Remission (CR) (<5% blasts in bone marrow (BM)) irrespective of the cytogenetic or molecular risk profile or MDS up to Refractory anemia with excess of blasts 2 (RAEB-2) (maximal 20% blasts in bone marrow) * Planned alloHSCT with Cluster of Differentiation 34+ (CD34+)-purified stem cell grafts after conditioning with fludarabine-melphalan-thio-thepa-ATG (ATG=Antithymocyte globulin) * HLA-matched stem cell donor (9 <= age <= 10/10, maximal 1 allel- or antigen mismatch allowed) without aberrant CD45RA (=Cluster of Differentiation) expression Additional patient inclusion criteria: Treatment phase patients at day 30 +/-5 after alloHSCT: *Stable engraftment of the allogeneic graft (granulocytes > 0.5*109/L) Donor * Donor must have met requirements of European Union (EU) Tissue and Cells Directive (2004/23/EC) (see below) * Healthy donor - having passed medical examination for stem cell donation * Donor must fulfill the requirements for allogeneic donor blood testing according to Richtlinie zur Herstellung und Anwendung von hämatopoetischen Stammzellzubereitungen (SC-Richtlinie (RILI) der Bundesärztekammer; 08/2014) * Donor informed consent for the additional non-mobilized apheresis * Written informed consent of the patient Exclusion Criteria: * Patient * Disease-specific treatment foreseen in the first 6 months after alloHSCT * Patients with AML M3 * Pregnant or lactating women * Severe psychological disturbances * Positive serology for Human immunodeficiency virus (HIV), Syphilis, West Nile Virus (WNV) * Participation in another interventional clinical trial during or within 4 weeks before study entry Additional patient exclusion criteria: Treatment phase patients at day 30 +/-5 after alloHSCT: * Disease specific treatment foreseen in the first 6 months after alloHSCT * Acute GVHD > grade I for which immune suppressive treatment is given * Progressive disease for which therapy is needed * Use of > 0,5 mg/kg bw prednisone a day * Life expectation < 12 weeks * End stage irreversible multi-system organ failure Donor * Donor pregnant or lactating * Donors with aberrant CD45RA isoform expression * General exclusion criteria for stem cell donation

NCT_ID NCT02758223

Study_NameProphylactic Application of Donor-derived TCM After Allogeneic HSCT

Study Objectives To safely reduce the burden of therapy in children, adolescents and young adults with mature B-NHL by reducing the number of intrathecal (IT) injections by the introduction of IT Liposomal Cytarabine (L-ARA-C, \[Depocyt®\]) and reducing the dose of anthracycline (doxorubicin) in good risk patients with the addition of rituximab to the FAB chemotherapy backbone (Immunochemotherapy). Conditions: Diffuse Large Cell Lymphoma, Burkitt's Lymphoma, High Grade B-cell Lymphoma Intervention / Treatment: DRUG: Rituximab, DRUG: IT Cytarabine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Newly diagnosed mature B-lineage (CD20 positive) Leukemia/Lymphoma * 1. Diffuse Large Cell Lymphoma (NOT primary mediastinal B-cell lymphoma) -2. Burkitt's Lymphoma * 3. High Grade B-cell Lymphoma---Burkitt's like. B-Cell Anaplastic Large cell Ki 1 positive lymphomas, Primary Mediastinal B-Cell Lymphoma (PMBL), and B-Lymphoblastic lymphomas are ineligible. No previous chemotherapy. Patients who have received emergency irradiation and/or steroid therapy will be eligible ONLY if started on protocol therapy not more than 72 hours from the start of radiotherapy or steroids. Bone marrow and cerebrospinal fluid MUST be obtained before steroids are given for patient to be eligible for the study. Exclusion Criteria: * Patients with newly diagnosed Group A (low risk) lymphoma. Patients with Group B (intermediate risk) if classified as Murphy Stage III/IV and diagnostic LDH > 2 XULN and patients with primary mediastinal B-cell lymphoma (PMBL). * Patients who have received any steroids in the week prior to diagnosis except as stated in Section 4.1.4 of the protocol. * No congenital or acquired immune deficiency. These patients are excluded due to the expected intense immunosuppression, increased risk of opportunistic infections, and higher expected septic death rate in this subgroup of patients with this proposed therapy. * No prior solid organ transplantation. * Patients with previous malignancies that have been treated with systemic chemotherapy with alkylator or anthracycline therapy. The latter group of patients are excluded due to an expected increase in late effects (eg. late cardiac toxicity, secondary malignancies, sterility, etc.). * Patients with known G6PD deficiency are NOT ELIGIBLE for Rasburicase therapy. Patients with G6PD deficiency should be treated with alkalinization, IV hydration and po and/or IV allopurinol during the reduction phase (COP). *2.6 Patients with serious (sepsis, pneumonia, etc..) proven or suspected infections at diagnosis will be excluded. *2.7 Pregnancy or Breast-Feeding: No information is available regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.

NCT_ID NCT01859819

Study_NameTreatment for Advanced B-Cell Lymphoma

Study Objectives Research Problem: Bladder cancer is one of the major health concerns of the world. The present methods of diagnosis are: Ultra sound, Cystoscopy, CT scan and urine cytology. All these are stressful to the patients, particularly Cystoscopy which is commonly employed for the follow up of Bladder cancer patients. Research Significance: The present study will employ a new photodynamic diagnostic procedure to quantify a certain cancer specific biomarker called Porphyrin, which selectively binds on to the bladder cancer tissues. In this context the present technique offer viable, very easy and reliable table top instrumentation for diagnosis and continual monitoring of disease regression through urine. Research Objectives: * To quantify bladder cancer specific biomarkers such as Porphyrin using photodynamic diagnostic procedure * To find out whether this technique might be a new and easy tool for bladder cancer diagnosis only by urine. Research Methodology: The bladder cancer patients is required to swallow a chemical called ALA (5 Amino levulinic Acid hydrochloride), about 10mg/kg body weight which will play a role of biological indicator. ALA gets metabolized into certain types of porphyrins which selectively bind on to the tumor tissues (for a longer time than the normal tissues). 5ml of blood and one urine samples will be taken before using ALA. The patient must drink water then the urine will be collected after 4, 8 and 12 hours of taking ALA and the samples will be analyzed by photodynamic diagnostic procedure. Conditions: Transitional Cell Carcinoma of the Bladder Intervention / Treatment: DRUG: Amino levulinic Acid Location: Saudi Arabia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: DIAGNOSTIC Allocation: NA Interventional Model: SINGLE_GROUP Masking: SINGLE

Inclusion Criteria: * Patients: Urothelial (transitional cell) carcinoma. Early and advanced stages of with transitional cell carcinoma of the bladder before transurethral resection of bladder Tumor (TURBT) . * Controls: Healthy volunteer's adults matched with age. Exclusion Criteria: * Urinary tract infection (UTI) patients * Cardiac patients

NCT_ID NCT02101931

Study_NameA Laser Detection for Bladder Cancer by (Photodynamic) Spectra of Urine

Study Objectives AEE788 is an orally active, reversible, small-molecule, multi-targeted kinase inhibitor with potent inhibitory activity against ErbB and VEGF receptor family of tyrosine kinases. It has an IC50 of less than 100 nM against p-EGFR, p-ErbB2, and p-KDR (VEGFR2). This study will assess the safety, pharmacokinetic (PK)/pharmacodynamic (PD) profiles and clinical activity of AEE788 in advanced cancers. Conditions: Cancer Intervention / Treatment: DRUG: AEE788 Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed solid tumor * Adequate hematologic, renal and hepatic function * Age >= 18 years * Karnofsky performance status score >= 70% * Life expectancy >= 12 weeks Exclusion Criteria: * Active brain metastases * Peripheral neuropathy > grade 2 * Diarrhea > grade 1 * Gastrointestinal (GI) dysfunction * Compromised cardiac function * Concurrent severe and/or uncontrolled medical conditions

NCT_ID NCT00118456

Study_NameStudy of Oral AEE788 in Adults With Advanced Cancer

Study Objectives This randomized phase II clinical trial evaluates the combination of a monoclonal antibody-based drug (SGN-15) with a chemotherapeutic agent compared to chemotherapy given alone in patients with non-small cell lung cancer that has failed at least one prior systemic therapy. The objective of the study is to determine the safety and clinical benefit, as measured by tumor response and quality of life, to the combination regimen. Monoclonal antibody therapy has been used in other types of cancer to target therapy to the tumor, thereby allowing for the chemotherapeutic agent to have a lesser effect on normal, healthy tissue. Conditions: Carcinoma, Non-Small-Cell Lung Intervention / Treatment: DRUG: SGN-15, DRUG: Docetaxel Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

INCLUSION CRITERIA: Patients with pathologically confirmed NSCLC which is metastatic or recurrent (non-resectable), who have failed at least one but no more than two prior therapies for advanced stage disease or have a recurrence within 6 months of completing adjuvant chemotherapy. Lewis-y antigen expression documented by immunohistochemistry for all patients. Patients must have: * Bidimensionally or unidimensionally measurable disease on the basis of physical exam or imaging studies, or * Evaluable disease: bone metastases defined on bone scan or malignant pleural effusion Performance status <= 2 (ECOG scale) with a life expectancy of at least 3 months Patients must be at least four weeks from prior treatment (chemotherapy, hormonal therapy, or definitive radiotherapy) EXCLUSION CRITERIA: Prior therapy with TAXOTERE (docetaxel) Cumulative anthracycline exposure > 300 mg/m2. More than one primary malignancy with the exception of: * Non-melanoma skin cancer * In situ carcinoma of the cervix * Localized prostate cancer * Completely resected stage I or II disease with no evidence of recurrent cancer from which the patient has remained disease free for more than 3 years. Uncontrolled significant non-malignant disease (e.g. congestive heart failure, bleeding, renal failure, hepatic failure). Uncontrolled, symptomatic brain metastasis. Peripheral neuropathy > grade 2. Concomitant therapy with other anti-neoplastic agents or experimental agents except for small volume radiation to a solitary bony metastasis. Active viral, bacterial or systemic fungal infections including known HIV or Hepatitis B or C. Women who are pregnant or breastfeeding Any serious underlying medical condition, which would impair the ability of the patient to receive the planned treatment including prior allergic reactions to recombinant human or murine proteins. Dementia or altered mental status that would prohibit the understanding and rendering of informed consent. Patients with uncontrolled peptic ulcer disease will be excluded.

NCT_ID NCT00051571

Study_NameSafety/Efficacy Study of Immunoconjugate With Docetaxel in Non-small Cell Lung Carcinoma

Study Objectives The formation of metastasis is responsible for as much as 90% of cancer-associated mortality. In spite of recent advances in oncologic therapy, approximately 50 % of the lung cancer patients have already overt disseminated cancer at diagnosis. Additionally, numerous patients with locoregional disease initially treated with curative intent develop (oligo)metastases during the course of disease. In both instances, these stage IV patients are generally considered to be incurable and mostly treated palliatively. Oligometastases, defined as 1-5 sites of active disease on whole body imaging, was coined to refer to isolated sites of metastasis resembling limited tumor metastatic capacity. The implication of this concept is that local cancer treatments are curative in a proportion of patients with metastases and that incorporating local therapy is a conceptually attractive approach. In several, but not all, academic centers the standard treatment of patients with oligometastases in good general health is standard chemotherapy followed by surgery or by Stereotactic Ablative Body Radiotherapy (SABR) with radical dose on the macroscopic visible tumors. The widespread introduction of SABR and of minimally invasive surgery has fuelled research in treating patients with oligometastases. Indeed, local control of metastases can be obtained in virtually all parts of the body with a low proportion of patients experiencing severe side effects. In the few prospective studies published to date, approximately 20% of patients remained free of recurrence several years after treatment when all sites of disease were targeted by radiation. Along with standard anti-cancer therapeutic modalities like chemotherapy and radiotherapy (RT), immunotherapy has recently gained a lot of attention. Angiogenesis is one of the hallmarks of cancer, and therefore, considerable efforts have been made to exploit this unique target for selective drug delivery. One of the appealing targets for both approaches is the splice variant of fibronectin containing extra domain B (EDB), which is abundantly expressed in vascular endothelial cells of a variety of primary tumors as well as metastases , but virtually absent in normal tissues. Recently, a human recombinant scFv fragment directed against EDB, designated L19, was developed and subsequently combined with the pro-inflammatory interleukin-2 (IL2), resulting in the immunocytokine L19-IL2. L19-IL2 delivers high doses of IL2 to the (metastatic) tumor site(s) exploiting the selective expression of EDB on newly formed blood vessels. Interleukin-2 (IL2) plays an essential role in the activation phases of both specific and natural immune responses. Even though it has no direct cytotoxic effects on cancer cells, it can induce tumor regression by stimulating a potent cell-mediated response. In summary, L19-IL2 is an immunocytokine which will stimulate immune response specifically in tumors with angiogenesis and tissue remodeling. Radiotherapy is a particularly interesting partner for immunotherapy, since it can be harnessed to specifically modify the immunogenicity of the primary tumors and their microenvironment, in the attempt to generate an in situ immunization of the host against a patient's own cancer. Our hypothesis is that three independent therapeutic approaches will synergize to improve dramatically survival in patients with oligometastases of solid tumors. Conditions: Solid Tumour Intervention / Treatment: DRUG: L19-IL2 Location: Netherlands Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion criteria: * Histological or cytological confirmed oligometastatic originating from NSCLC, HNSCC, CRC, RCC and melanoma occurring synchronous (at time of diagnosis) or metachronous (> 6 months after radical treatment for primary tumor; i.e., surgically. A biopsy could be omitted in selected cases if a biopsy is medically contraindicated or unfeasable (e.g. fear of ent-metastasis, lesion not accessible). In this case the diagnosis of metastatic disease should be certified using an alternative approach (e.g. imaging..) * determination of possible activating mutations (e.g., ALK/EGFR/ROS in NSCLC, and BRAF, NRAS and KIT in melanoma); * All oligometastatic tumor sites (including brain) are eligible; * <= 5 metastases, or 4 if the primary tumor is to be treated concomitantly; * <= 3 metastatic lesions confined to one organ; * <= 2 organ systems affected with metastases; * WHO performance status 0 <= age <= 2; * Adequate bone marrow: Normal white blood cell count and formula, normal platelet count, no anemia requiring blood transfusion or erythropoietin; * Adequate hepatic function: total bilirubin <= 1.5 x upper limit of normal (ULN) for the institution; ALT, AST, and alkaline phosphatase <= 2.5 x ULN for the institution); * Adequate renal function: calculated creatinine clearance at least 60 ml/min; * The patient is capable of complying with study procedures; * Signed and dated written informed consent; * Life expectancy of at least 12 weeks; * For women of childbearing potential, a negative pregnancy test prior to the first dose of study treatment; * Men and women with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 12 weeks after the last dose of study medication. Exclusion criteria * Other oligometastatic (hormone-sensitive) solid tumors; * Previous radiotherapy to an area that would be re-treated by SABR; * Previous systemic treatment to treat recurrent disease; * Other active malignancy or malignancy within the last 2 years (with exception of localized skin basal/squamous cell carcinoma, bladder in situ carcinoma); * History of allergy to intravenously administered proteins/peptides/antibodies; * HIV infection, active infection, or active hepatitis; * Chronic use of corticosteroids used in the management of cancer or non-cancer-related illness; * Acute or sub-acute coronary syndromes within the last year, accute inflammatory heart disease, heart insufficiency or irreversible cardiac arrhythmias; * Impaired cardiac function defined as left ventricular ejection fraction (LVEF) <50% (or below the study site's lower limit of normal) as measured by MUGA of ECHO. (LVEF measurements dating back up to 8 weeks will be acceptable in the absence of intercurrent use of potentially cardiotoxic treatment of cardiac medical history * Uncontrolled hypertensive disease * History or evidence of active autoimmune disease; * Severe diabetic retinopathy (38); * Major trauma including surgery within 4 weeks prior to entering the study; * Any underlying medical or psychiatric condition which in the opinion of the investigator will make administration of study drug hazardous or hinder the interpretation of study results (e.g., AE); * Unstable or serious concurrent uncontrolled medical conditions; * Pregnancy or breast-feeding.

NCT_ID NCT02086721

Study_NamePhase I Clinical Study Combining L19-IL2 With SABR in Patients With Oligometastatic Solid Tumor

Study Objectives To evaluate efficacy, safety, and pharmacokinetics of BAY 43-9006 in patients with unresectable and/or metastatic renal cell cancer (RCC) who have failed at least one cytokine containing regimen. Conditions: Carcinoma, Renal Cell Intervention / Treatment: DRUG: Nexavar (Sorafenib, BAY43-9006) Location: Japan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients who suffer from unresectable and/or metastatic, measurable RCC histologically or cytologically documented. * Patients with rare subtypes of RCC, such as pure papillary cell tumor, mixed tumor containing predominantly sarcomatoid cells, Bellini carcinoma, medullary carcinoma, or chromophobe oncocytic tumors, are excluded from study participation. Exclusion Criteria: * More than three regimens of previous treatment for RCC

NCT_ID NCT00661375

Study_NameBAY43-9006 Phase II Study for Renal Cell Carcinoma

Study Objectives This trial will be conducted to explore the biological effects in the skin following treatment with PEP005 Gel, 0.05% administered for two consecutive days, assessed by reflectance confocal microscopy. Conditions: Actinic Keratosis Intervention / Treatment: DRUG: Ingenol mebutate, DRUG: Placebo Gel Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Male or female subjects at least 18 years * Subjects with AK lesions and subclinical AK lesions within a contiguous 25 cm2 area on the upper extremity * Subjects must have a 25 cm2 area of normal skin on the inner upper arm * Female subjects must be of either: * Non-childbearing potential, post-menopausal, or have a confirmed clinical history of sterility or * Childbearing potential, with a confirmed negative urine pregnancy test prior to exposure. * Female subjects of childbearing potential must be willing to consent to using high effective methods of contraception * Ability to follow trial instructions and likely to complete all trial requirements * Obtained written informed consent prior to any trial-related procedures Exclusion Criteria: * Location of the selected treatment areas: * Within 5 cm of an incompletely healed wound or infected area of the skin * Within 10 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma(SCC) * History or evidence of skin conditions other than the trial indication that would interfere with evaluation of the investigational product * Clinical diagnosis/history or evidence of any medical condition that would expose a subject to an undue risk of a significant AE or interfere with assessments of safety during the course of the trial, as determined by Investigator clinical judgment * Anticipated need for in-patient hospitalisation or in-patient surgery during the trial period. * Current participation in any other interventional clinical trial * Subjects who have received treatment with any non-marketed drug product within the last two months * Previous enrolment in this clinical trial * Prohibited Therapies and/or Medications 2 weeks prior to the Screening visit within 2 cm of selected treatment area: *Cosmetic or therapeutic procedures *Use of acid-containing therapeutic products * Use of topical salves or topical steroids * Prohibited Therapies and/or Medications: within 4 weeks prior to the Screening visit: * Treatment with immunomodulators, cytotoxic drugs or interferon/interferon inducers,systemic medications that suppress the immune system, or with UVB * Prohibited Therapies and/or Medications: within 8 weeks prior to the Screening visit: * Treatment with 5-FU, imiquimod, diclofenac, or photodynamic therapy: within 2 cm of the selected treatment areas. * Use of systemic retinoids

NCT_ID NCT01449513

Study_NamePEP005 Gel - Biological Effects in Actinic Keratosis Assessed by Reflectance Confocal Microscopy

Study Objectives Second-line induction therapy with fludarabine, idarubicin, cytarabine,Granulocyte colony-stimulating factor (G-CSF) and plerixafor, in patients with relapsed or refractory Acute Myeloblastic Leukemia (AML) aged 65 or younger. Conditions: Acute Myeloblastic Leukemia Intervention / Treatment: DRUG: fludarabine, DRUG: Idarubicin, DRUG: cytarabine, DRUG: G-CSF, DRUG: plerixafor Location: Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Diagnosis of AML according to the WHO criteria * Relapsed or refractory AML as defined below First relapse after standard treatment with duration of the first remission less than year * Refractoriness to an induction cycle that includes cytarabine and anthracyclines * Nonpromyelocytic leukemia (absence of t(15;17) or PML-RARα rearrangement and its variants) * Peripheral blood blast cell count less than 50 x 109/L. Hydroxyurea and leukopheresis can be used to lower the blast count prior to beginning treatment * Age <= 65 years and >= 18 years * ECOG performance status of 0 <= age <= 2 * Provide signed written informed consent * Be able to comply with study procedures and follow-up examinations * Be nonfertile or agree to use birth control during the study through the end of last treatment visit * Adequate renal and hepatic function as indicated by all of the following: Total bilirubin <1.5 x Institutional Upper Limit of Normal (ULN); and AST and ALT <2.5 xULN; and Serum creatinine <1.0 mg/dL; if serum creatinine <1.0 mg/dL, then, the estimated glomerular filtration rate (GFR) must be <60 ml/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation - Minimal impairment of cardiac function as measured by at least 1 of the following: Left ventricular ejection fraction (LVEF) >40% on multigated acquisition (MUGA) scan or radionuclide angiographic scan; or Left ventricular fractional shortening >22% on echocardiography exam; Exclusion Criteria: * Diagnosis of acute promyelocytic leukemia (APL, French-American-British [FAB] classification M3 or WHO classification of APL with t(15;17)(q22;q12), (PML/RARalfa and variants) * AML secondary to previous treatment for myelodysplastic syndrome (MDS) * Peripheral blood blast cell count >= 50 x 109/L. Hydroxyurea and leukopheresis can be used to lower the blast count prior to beginning treatment * Prior investigational treatment within 30 days prior to the first dose of study drug. If any investigational treatment has been received prior to this time point, drug related toxicities must have recovered to Grade 1 or less prior to first dose of study drug * Prior hematopoietic stem cell transplant (HSCT) (previous autologous hematopoietic stem cell transplant is allowed) * Investigational agent received within 5 days prior to the first dose of study drug. If received any investigational agent prior to this time point, drug-related toxicities must have recovered to Grade 1 or less prior to first dose of study drug * Impaired renal and liver function as indicated by the following: Total bilirubin > 1.5 x upper limit of normal (ULN) provided that this is not attributable to AML itself; or AST and ALT > 2.5 xULN provided that this is not attributable to AML itself; or Serum creatinine > 1.0 mg/dL provided that the estimated glomerular filtration rate (GFR) is <= 60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation * Impaired cardiac function as measured by at least 1 of the following: Left ventricular ejection fraction (LVEF) < 40% on multigated acquisition (MUGA) scan or radionuclide angiographic scan; or Left ventricular fractional shortening < 22% on echocardiography exam; * Poor overall condition ECOG 3 <= age <= 4 * Refusal to sign the informed consent * Unable to comply with study procedures and follow-up examinations * Psychiatric disorders that could interfere with consent, study participation or follow-up * Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) * Diagnosis of another malignancy, unless the patient has been disease-free for at least 5 years following the completion of curative intent therapy with the following exceptions: Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed * Clinical evidence suggestive of central nervous system (CNS) involvement with leukemia unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal fluid (CSF) * Prior positive test for the human immunodeficiency virus (HIV) * History of hypersensitivity to any of the study drugs

NCT_ID NCT01435343

Study_NameTreatment of Relapsed or Refractory Acute Myeloblastic Leukemia

Study Objectives This is a multicenter, open-label Phase 1 study of orally administered CB-5339 in participants with R/R AML or participants with R/R intermediate- to high-risk MDS. Conditions: Acute Myeloid Leukemia, in Relapse, Myelodysplastic Syndromes Intervention / Treatment: DRUG: CB-5339 Location: United States, Australia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Male or female and >= 18 years at the time of signing the consent form * One of the following advanced hematologic malignancies including: * Relapsed or refractory AML as defined by 2016 WHO criteria and are not candidates for curative therapies such as allogeneic hematopoietic cell transplant or for whom there is no standard of care therapy available that is likely to lead to disease remission according the investigator * MDS high-very high risk by the revised international scoring system for evaluating prognosis in myelodysplastic syndromes that is recurrent or refractory or the participant is intolerant to established therapy known to provide clinical benefit for their condition (e.g., relapsed following treatment with hypomethylating agent or lack of response after > 4 cycles), according to treating physician. Potential participants who meet the criteria for intermediate risk may be considered with approval by the medical monitor if the participant has severe cytopenia(s) and/or elevated bone marrow blast counts. * Adequate organ function defined as: * Serum creatinine <=1.5 mg/dL or an estimated glomerular filtration rate of >=60 mL/min as calculated by the Cockcroft-Gault glomerular filtration rate equation * Total bilirubin <= 1.5 × the upper limit of normal (ULN) unless considered due to Gilbert's disease or leukemic disease * Aspartate aminotransferase (AST) <=3 × the ULN; alanine aminotransferase (ALT) <=3 × the ULN. Levels of AST and/or ALT <=5 × the ULN may be acceptable for participants with known leukemic involvement of the liver after discussion with the study medical monitor * Eastern Cooperative Oncology Group (ECOG) performance status <=2. * Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If of childbearing potential, agree to use an effective barrier method of birth control (i.e., latex condom, diaphragm, cervical cap, etc.) to avoid pregnancy during the study and 90 days after the last dose of CB-5339. Female participants of childbearing potential need a negative serum or urine pregnancy test within 7 days of study enrollment. Non-childbearing is defined as >= 1 year postmenopausal or surgically sterilized * Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol Exclusion Criteria: * Acute promyelocytic leukemia with t(15;17)(q22;q12); or abnormal promyelocytic leukemia/retinoic acid receptor alpha (PML-RARA). * Participants with clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if there is a clinical suspicion of CNS involvement by leukemia during screening. * Participants with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation. * Concomitant malignancy, requiring active treatment, except for basal-cell or squamous cell carcinoma of the skin, carcinoma-in-situ of the uterine cervix, or localized prostate cancer. * Adjuvant therapy for breast cancer or prostate cancer is allowed. * Active, uncontrolled, systemic infection or severe localized infection during screening or prior to Cycle 1 Day 1 (C1D1; unless considered due to tumor by the investigator). * Note, participants receiving prophylactic anti-infectives are allowed on study. * Known human immunodeficiency virus (HIV) infection with CD4+ T cell counts <350 cells/μL, initiation of antiretroviral therapy within 4 weeks before C1D1, or acquired immunodeficiency syndrome (AIDS)-related infection within 12 months before C1D1. * Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with viral load above the limit of quantification * Major cardiac abnormalities as defined but not limited to the following: uncontrolled angina or unstable life-threatening arrhythmias, history of myocardial infarction within 12 weeks prior to Baseline, Class 3 or higher New York Heart Association (NYHA) congestive heart failure, or left ventricular ejection fraction (LVEF) <45% as measured by echocardiogram (ECHO) within 28 days of C1D1 * Persistent (3 consecutive ECGs performed >=5 minutes apart) prolongation of the corrected QT interval by Fredericia's method (QTcF) to > 480 msec * Gastrointestinal conditions that may interfere with the absorption of orally-administered drugs including but not limited to short gut syndrome, gastroparesis, inflammatory bowel disease, or acute pancreatitis. * Any other severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or CB-5339 administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, may interfere with the interpretation of the study results and, in the Investigator's opinion, or would make the participant inappropriate for entry into this study * A condition that is expected to require concomitant use of any medication listed as prohibited while on study. * Known hypersensitivity to any components of CB-5339. * Use of chemotherapy (except hydroxyurea), radiation or monoclonal antibodies within 14 days or 5 half-lives for small molecule inhibitors prior to first dose of CB-5339 * Participants who have undergone a hematopoietic cell transplant (HCT) within 100 days of the first dose of CB-5339, or participants on immunosuppressive therapy post-HCT at the time of screening, use of calcineurin inhibitors within 4 weeks prior to first dose of CB-5339, or with clinically significant graft-versus-host disease (GVHD). * Note: The use of topical steroids or <10mg oral prednisone for ongoing skin GVHD is permitted. * Major surgery within 4 weeks prior to first dose of CB-5339. Participant must have recovered from surgery and be without current complications of infection or dehiscence * Enrollment in other clinical trials unless approved by Medical Monitor

NCT_ID NCT04402541

Study_NameStudy of CB-5339 in Acute Myeloid Leukemia or Myelodysplastic Syndrome

Study Objectives The purpose of this study is to see whether the combination for RAD001 and Nexavar® works better when given together than they do alone. The purpose of the first phase of this study is to determine the best dose of RAD001 given with Nexavar®, and to see what effects, good and/or bad, the study drug has on the subject and the subject's tumor. This study will also observe side effects experienced by the subject. Conditions: Carcinoma, Renal Cell Intervention / Treatment: DRUG: RAD001, DRUG: Sorafenib Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologic confirmed predominant clear cell renal cell carcinoma. * Patients must have progressive metastatic disease. * Paraffin RCC tissue blocks or unstained slides must be available. * Karnofsky performance status > 70% . * Not pregnant * Age > 18 * Initial laboratory values must meet requirements * Phase I: No more than three prior systemic and/or investigative therapy for MRCC. Previous therapy may include prior single agent exposure to RAD001 or Nexavar®. Four weeks must have elapsed from previous therapy. * Phase II: No more than one prior systemic and/or investigative therapy of any kind for MRCC. Four weeks must have elapsed from previous therapy. * Phase II: Previous therapy may not include RAD001 or Nexavar®. * Phase II: Patients with primary tumor in place are strongly encouraged to undergo nephrectomy prior to initiation of study agent. * Phase II: Prior palliative radiotherapy to metastatic lesion(s) is permitted. Patient must have adequately recovered from the acute toxicities of this treatment. * Phase II: All major surgery of any type and/or radiotherapy must be completed at least 4 weeks prior to registration. Exclusion Criteria: * No ongoing hemoptysis or cerebrovascular accident within 12 months, or peripheral vascular disease with claudication on less than 1 block, or history of clinically significant bleeding. * No deep venous thrombosis or pulmonary embolus within one year and no ongoing need for full-dose oral or parenteral anticoagulation. * No evidence of current central nervous system (CNS) metastases. * No significant cardiovascular disease * No patients with uncontrolled hypertension * Any ongoing requirement for systemic corticosteroid therapy (except replacement therapy for adrenal insufficiency) or other immunosuppressants are not permitted. * Patients with a pre-existing thyroid abnormality whose thyroid function cannot be maintained in the normal range by medication are ineligible. * No uncontrolled psychiatric disorder. * Patients with delayed healing of wounds, ulcers, and/or bone fractures are not eligible. * Patients with a 'currently active' second malignancy other than non-melanoma skin cancers are not eligible. Patients are not considered to have a 'currently active' malignancy if they have completed anti-cancer therapy and are considered by their physician to be a less than 30% risk of relapse. * Pregnant women are excluded * All fertile patients must use adequate contraception (barrier method) while on study and for three months thereafter. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. * Prior treatment with any investigational drug within the preceding 4 weeks. * Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, severe infection, severe malnutrition, ventricular arrhythmias, chronic liver or renal disease, active upper GI tract ulceration). * A known history of HIV seropositivity. * Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).

NCT_ID NCT00448149

Study_NamePhase I/II Trial of RAD001 Plus Nexavar in Patients With Kidney Cancer

Study Objectives The purpose of this study is to determine whether oral rucaparib is effective in the treatment of patients with locally advanced or metastatic pancreatic cancer and a known deleterious BRCA mutation. Conditions: Pancreatic Cancer, Pancreatic Ductal Adenocarcinoma Intervention / Treatment: DRUG: Rucaparib Location: Israel, United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Confirmed diagnosis of pancreatic cancer (ductal adenocarcinoma and related subtypes eligible; endocrine and neuroendocrine tumors excluded) * Received at least 1, but no more than 2, chemotherapy-based regimens for locally advanced or metastatic disease and has relapsed or progressive disease. Patients no longer able to continue treatment with chemotherapy due to intolerable toxicity may be considered for study participation provided that radiology assessment confirms either stable disease or disease progression (i.e. no response to treatment) * Documented deleterious or suspected deleterious (or equivalent interpretation) BRCA mutation (germline or somatic) as assessed by a local laboratory * Measurable disease Exclusion Criteria: * Presence of another active cancer * Prior treatment with any PARP inhibitor, including rucaparib. Patients treated with prior iniparib are eligible. * Symptomatic and/or untreated central nervous system metastases. * Clinical evidence of malabsorption and/or any other gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with the absorption of rucaparib.

NCT_ID NCT02042378

Study_NameA Study of Rucaparib in Patients With Pancreatic Cancer and a Known Deleterious BRCA Mutation

Study Objectives This is a phase I study evaluating tolerability, pharmacokinetics, and preliminary efficacy of HC-1119 in patients with metastatic castration-resistant prostate cancer. The study objective is to study the tolerability, safety, and dose-limiting toxicities (DLT) of HC-1119 in patients with mCRPC. Conditions: Metastatic Castration Resistant Prostate Cancer Intervention / Treatment: DRUG: HC-1119 Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria (those who meet all of the following are eligible): * Voluntarily participated in the study, with understanding of relevant study procedures and signed informed consent form; * Male , >=18 years; * With histologically or cytologically confirmed prostate cancer, without neuroendocrine carcinoma or ductal adenocarcinoma; * With evidence of metastatic disease (such as bone scan and CT/MRI results); * Patients with relapsed, refractory, or progressive disease despite castration (surgery or chemical) or combined androgen deprivation therapy (Progressive disease is defined as 1 or more of the following 3 criteria: Serum PSA progression: A minimum of 3 rising PSA values with an interval of at least 1 week between determinations, resulting in a final value higher than 50% of the minimum, with a starting PSA value > 2 ng/ml; Soft tissue disease progression as defined by RECIST 1.1; Bone disease progression defined by PCWG2 with 2 or more new metastatic lesions on bone scan); * Castrate levels of testosterone (< 50 ng/dl) at screening; * Bilateral orchiectomy or ongoing androgen deprivation therapy with effective GnRH analogues; * Estimated life expectancy > 6 months; * ECOG performance status <= 1; * Laboratory tests must meet the following criteria: 1. Routine Blood Test: hemoglobin (Hb) >= 90 g/L (no blood transfusion within the last 14 days); absolute neutrophil count (ANC) >= 1.5 x 109/L; platelet count (PLT) >= 80 x 109/L; 2. Blood Biochemistry: creatinine (Cr) <= 2 x upper limit of normal (ULN), or Cr > 2 x ULN but the calculated CrCl >= 60 mL/min; bilirubin (BIL) <= 2 x ULN; alanine aminotransferase (ALT), aspartate aminotransferase (AST) <= 2.5 x ULN (or <= 5.0 x ULN for patients with liver metastases); 3. Coagulation: INR < 1.5. Exclusion Criteria (those who meet any one of the following are ineligible): * Ongoing toxicity ( >= Grade 2 toxicity) from previous treatments; * Clinically significant GI dysfunction which may affect the intake, transport, or absorption of drug (such as inability to swallow, chronic diarrhea, and bowel obstruction, etc.), or patients with complete gastrectomy; * History of allergies, or known hypersensitivity to components of the investigational drug; * Brain metastases; * Other malignancies within the last 5 years (except for curatively treated non-melanoma skin cancer); * History of organ transplants * HIV seropositive; * Past medical history of seizures or serious CNS diseases; * History of unexplained coma; * Family history of seizures; * History of traumatic brain injury; * History of medication or drug abuse; * Patients with severe cardiovascular diseases, including those with myocardial infarction, arterial thrombosis, unstable angina, or clinical symptomatic heart failure within the past 6 months; * Uncontrolled hypertension (systolic >= 160 mmHg or diastolic >= 100 mmHg). Patients with a history of hypertension is eligible if his blood pressure is controlled with antihypertensives; * Medications that lower the seizure threshold must be used during the study; * Treatment with 5α-reductase inhibitors (finasteride, dutasteride), estrogen, or cyproterone within the past 4 weeks; * Treatment with ketoconazole within the past 4 weeks; * Previously treated with investigational or approved medications that inhibit testosterone synthesis (such as abiraterone acetate, TAK-683, and TAK-448) or target testosterone receptors (such as enzalutamide, SHR3680, proxalutamide, and ARN509); * Participated in other clinical trials within 1 month prior to enrollment; * Subjects is determined by the investigator to be unsuitable for this study.

NCT_ID NCT03774056

Study_NameA Study Evaluating Tolerability, Pharmacokinetics, and Preliminary Efficacy of HC-1119 in Patients.

Study Objectives The purpose of this study is to evaluate the safety and efficacy of NOX A12 in combination with a background therapy of bendamustine and rituximab (BR) chemotherapy in previously treated patients with chronic lymphocytic leukemia (CLL). Conditions: Chronic Lymphocytic Leukemia Intervention / Treatment: DRUG: NOX-A12 Location: Belgium, France, Austria, Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Diagnosis of B-cell CLL * Relapsed, bendamustine-sensitive (at least partial response with a duration of at least six months) or bendamustine-naive patients after at least one but not more than 3 prior treatments of their disease. * CLL in need of treatment (Binet C or A/B with active disease) according to Hallek et al. 2008 * Subject must have measurable disease according to NCI-WG criteria (for details see Hallek M, Blood 2008; 111: 5446 <= age <= 5456). * Pre-study WHO performance status <= 2 and modified cumulative illness rating score (CIRS) of less than 7. * Signed, written informed consent. * Men and women of reproductive potential must agree to follow accepted birth control methods during treatment and for 3 months after completion of treatment. * Acceptable liver function: Bilirubin <= 1.5 x upper limit of normal (ULN) at screening, AST (SGOT) and/or ALT (SGPT) <= 2.5 x ULN. * Acceptable hematologic status: Platelet count >= 75 x 109/L, ANC > 0.75x109/L. * Acceptable renal function: Serum creatinine <=1.5 ULN and/or calculated creatinine clearance (Cockroft-Gault Formula) >= 50 mL/min * Male or female, age >= 18 * No clinically significant abnormalities of liver volume, liver hemodynamics or elasticity, measured by abdominal ultrasound. Exclusion Criteria: * Relapse of B-cell CLL within 12 months after last chemotherapy. * Subjects who have progressed to more aggressive B-cell cancers such as Richter's syndrome. * CLL with documented loss of the short arm of chromosome 17 (17p-) associated with the loss of p53. * The subject has a history of or is clinically suspicious for cancer-related Central Nervous System disease. * Patients at risk of hemostasis or spleen rupture. * Autoimmune hemolytic anemia. * Prior allogeneic stem cell transplant (alloSCT) or patients who are considered to be candidates for allo SCT as assessed by their treating physician * Patient has a history of other active malignancies within three years prior to study entry, with the exception of: adequately treated in situ carcinoma of the cervix uteri; basal or squamous cell carcinoma of the skin; in situ carcinoma of the bladder; previous malignancy confined and surgically resected with curative intent. * The patient exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to: uncontrolled systemic infection (viral, bacterial, or fungal); diagnosis of fever and neutropenia within 1 week prior to study drug administration. * Female subject is pregnant or breast-feeding. * Known infection with HIV, active Hepatitis B or Hepatitis C. * The patient has a history of prior toxicity from bendamustine or rituximab that resulted in permanent discontinuation of treatments. * Treatment with other investigational drugs, or participation in another clinical trial within 30 days prior to study drug administration. * Uncontrolled hypertension (defined as systolic blood pressure (BP) > 160 mm Hg or diastolic BP > 100 mm Hg). * Myocardial infarction or unstable angina within the past 6 months prior to study drug administration. * Systemic illnesses or other severe concurrent disease including alcoholism which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and efficacy of the investigational treatments. * Known or suspected of not being able to comply with the trial protocol. * Having been previously enrolled in this clinical trial. * Known hypersensitivity to rituximab or to any of the excipients or to murine proteins * History of recurring or chronic infections or underlying conditions which may further predispose patients to serious infection. * Known hypersensitivity to bendamustine or to mannitol. * Invasive surgery within 30 days prior to study drug administration.

NCT_ID NCT01486797

Study_NameNOX-A12 in Combination With Bendamustine and Rituximab in Relapsed Chronic Lymphocytic Leukemia (CLL)

Study Objectives Colon resection is one of the major surgery, the postoperative pain is so severe that it is necessary to use additional analgesics as well as a patient controlled analgesia (PCA). The most common pain management of this surgery is the intravenous (IV) PCA. If it is relatively insufficient amount of narcotic analgesics ,in the case of IV PCA, may be failed to reduce the pain effectively. Consequently, it may result in the a lot of rescue analgesics use, which leads to the adverse effects in patients who are very sensitive to narcotic analgesics. And the patient's satisfaction to the PCA may be low. For the recently released PCA instrument 'PAINSTOP', the investigators can specify the mode setting including total volume, flow rate (basal rate) per hour, bolus dose, and lock out time (LOT). Furthermore, this device can be set to optimize basal infusion (B.I), which is a new mode, so that the administered rate and amount of drug can be increased or decreased according to the patient's use of bolus button. Therefore, this PCA device can be implemented to the conventional mode, and added the function of automatically controlling the basal rate and administered amount of drug according to the use demand of the patient. However, since there are few studies related to this new mode of PCA, more research is needed in patients with postoperative pain. Conditions: Colon Cancer Intervention / Treatment: OTHER: Optimizing B.I (New) PCA mode, OTHER: Conventional PCA mode Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: OTHER Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * The subjects who undergoing colon resection due to colon cancer * ASA class Ⅰ-Ⅲ * Written consents obtained to participate voluntarily in this clinical trial Exclusion Criteria: * Sudden change of surgical plan * Patients who have the hypersensitivity to the pain killers including narcotics * Patients who are unable to express the degree of pain

NCT_ID NCT03011359

Study_NameThe Comparison of Postoperative Pain After Colon Resection in Intravenous Patient-controlled Analgesia Between Conventional Mode and Optimizing B.I Mode With 'PAINSTOP' Equipment

Study Objectives Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Phase II trial to study the effectiveness of tipifarnib in treating older patients who have previously untreated acute myeloid leukemia Conditions: Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Erythroid Leukemia (M6), Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1), Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Acute Myelomonocytic Leukemia (M4), Adult Erythroleukemia (M6a), Adult Pure Erythroid Leukemia (M6b), Cellular Diagnosis, Adult Acute Myeloid Leukemia, Untreated Adult Acute Myeloid Leukemia Intervention / Treatment: DRUG: tipifarnib, OTHER: laboratory biomarker analysis Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Pathologic confirmation of the diagnosis of AML (>= 20% marrow blasts) * ECOG performance status 0 or 1 * Patients must be able to give informed consent * SGOT and SGPT =< 2.5 x normal limits (grade 1) * Serum creatinine =< 1.5 x normal limits (grade 1) * AML (any of the following): * Newly diagnosed AML in adults >= 75 years * Newly diagnosed AML arising from MDS in adults >= 65 years * Hyperleukocytosis with >= 30,000 leukemic blasts/uL Exclusion Criteria: * Acute promyelocytic (FAB M3) subtype * Previously treated with chemotherapy for leukemia (except for hydroxyurea) * Disseminated intravascular coagulation (laboratory or clinical) * Active central nervous system leukemia * Concomitant radiation therapy, chemotherapy, or immunotherapy; previous therapy for another malignancy is permitted, provided that at least 1 month has occurred since patient received any of these treatments * Intrinsic impaired organ function (as stated above) * Symptomatic neuropathy (grade 2 or worse) * Known allergy to imidazole drugs, such as ketoconazole, miconazole, econazole, teconazole, clotrimazole, fenticonazole, isoconazole, sulconazole, or ticonazole * Physical or psychiatric conditions that in the estimation of the principal investigator (PI) or designee place the patient at high risk of toxicity or non-compliance, e.g. severe congestive heart failure (CHF), unstable angina, or poorly controlled psychosis

NCT_ID NCT00027872

Study_NameTipifarnib in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

Study Objectives This study is for newly diagnosed WHO Grade IV malignant glioma patients to determine whether an investigational drug known as marizomib (MRZ) will improve the treatment of newly diagnosed glioblastoma patients by delaying the growth of the cancer, reducing the size of the tumor, and/or improving survival. Marizomib (MRZ) is being added to standard-of-care treatments of radiotherapy (RT), temozolomide (TMZ), and Optune. Conditions: Glioblastoma, Malignant Glioma Intervention / Treatment: DRUG: MRZ, DRUG: TMZ, RADIATION: RT, DEVICE: Optune Location: Canada, United States, Switzerland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Signed Informed Consent Form * Males and females of age >= 18 years or of age >= 22 years for those assigned to Optune™ at the time of signing of the informed consent document. * Histologically confirmed newly diagnosed G4 MG * Karnofsky Performance Status (KPS) score >= 70% * For Concomitant Treatment: Prior tumor resection or biopsy up to 8 weeks prior to first MRZ dose * For Adjuvant Treatment: All AEs resulting from surgery must have resolved to NCI-CTCAE (v. 4.03) Grade <= 1 * Stable or decreasing dose of corticosteroids over 14 days prior to first MRZ dose * For Concomitant Treatment: No prior treatment with MRZ or any other PIs, including BTZ, carfilzomib (CFZ), or ixazomib (IXZ) * For Adjuvant Treatment: No prior treatment with BTZ, CFZ, or IXZ * No investigational agent within 4 weeks prior to first dose of study drug * Adequate hematological, renal, and hepatic function * Patients must be without seizures for at least 14 days prior to enrollment, and patients who receive treatment with AEDs must be on stable doses for at least 14 days prior to enrollment * Absence of known HIV infection, chronic hepatitis B, or hepatitis C infection; absence of any other serious medical condition which could interfere with oral medication intake * Patients with archival tumor tissue suitable for measurement of proteasome activity and biomarker status must give permission to access and test the tissue. Patients without archival tumor tissue are eligible for the Dose-Escalation stage, but not the Dose-Expansion stage of the study * For women of child-bearing potential and for men with partners of child-bearing potential, patient must agree to take contraceptive measures for duration of treatments and for one month after last study treatment * Willing and able to adhere to the study visit schedule and other protocol requirements Exclusion Criteria: * Co-medication or concomitant therapy that may interfere with study results * History of thrombotic or hemorrhagic stroke or myocardial infarction within 6 months * Other chemotherapy or anti-tumor treatment for brain tumor (other than therapies required by the inclusion criteria of this protocol) * Pregnant or breast feeding * Uncontrolled intercurrent illness that would limit compliance with study requirements, or disorders associated with significant immunocompromised state * Known other previous/current malignancy requiring treatment within <= 3 years except for liited disease treated with curative intent * Any comorbid condition that confounds the ability to interpret data from the study as judged by the Investigator or Medial Monitor * For those enrolled in Adjuvant Treatment with Optune™, patients are excluded if they are < 22 years, have an active implanted medical device, a skull defect, bullet fragments in the head, sensitivity to conductive hydrogels, a scalp condition that might interfere with wearing the device, or GBM that is not supratentorial.

NCT_ID NCT02903069

Study_NameStudy of Marizomib With Temozolomide and Radiotherapy in Patients With Newly Diagnosed Brain Cancer

Study Objectives This study is designed to compare between intravenous infusion of dexmedetomidine and intravenous infusion of lidocaine in reduction of proinflammatory cytokines as IL-6 and TNF-α, some stress reactions (serum insulin and serum lactate),and postoperative analgesic requirements in patients undergoing surgery for pelviabdominal cancers. Conditions: Inflammatory Response Intervention / Treatment: DRUG: dexmedetomidine infusion, DRUG: lidocaine infusion, DRUG: Placebos Location: Egypt Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * American society of anesthesia (ASA) Physical Status classification: ASA II physical status. * Age between 18 <= age <= 60 old. * Patients who will undergo major pelviabdominal surgery. Exclusion Criteria: * Patient refusal. * Allergy to local anesthetics. * Cognitive disorders. * uncontrolled diabetes or hypertension.

NCT_ID NCT04148599

Study_NameEffect of IV Infusion of Lidocaine Compared to IV Infusion of Dexmedetomidine on Proinflammatory Cytokines

Study Objectives Primary Objectives: * To determine the safety, toxicity and the maximum tolerated dose (MTD) of intravenous STA-5312 when administered weekly (3 of 4 weeks) to subjects with advanced or metastatic solid tumors. * To determine the pharmacokinetics of STA-5312. Secondary Objective: • To assess antitumor activity of STA-5312 administration. Conditions: Advanced or Metastatic Solid Tumors Intervention / Treatment: DRUG: STA-5312 Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Male and female subjects aged at least 18 years with histologically-confirmed non hematological malignancy that is metastatic or unresectable and for which no standard therapy exists. * Eastern Cooperative Oncology Group (ECOG) Performance status of 0 <= age <= 2. * Peripheral neuropathy less than Grade 2 on National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3 adverse event scale. * Subjects must have acceptable organ and marrow function during the Screening Period as defined below. (Note: Subjects must meet these criteria at each pre-dose visit to receive additional doses of STA-5312). * Absolute neutrophil count (ANC) greater than 1500 cells/µL * Platelets greater than 100,000/µL * Total bilirubin must be <1.5 times ULN * Aspartate transaminase (AST) <=3 times ULN or less than 5 times the ULN in subjects with liver metastases * Alanine transaminase (ALT) <=3 times ULN or less than 5 times the ULN in subjects with liver metastases * Adequate renal function (serum creatinine <2.0 mg/dL). * Electrocardiogram (ECG) without evidence of clinically significant ventricular arrhythmias or active ischemia as determined by the investigator. * Documented cardiac ejection fraction greater than 50% obtained within 30 days of administration of the first dose. * The effects of STA-5312 on the developing human fetus are unknown. Therefore, women of childbearing potential (defined as women > 50 years or history of amenorrhea for <12 months prior to study entry) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a female subject become pregnant or suspect she is pregnant while participating in this study, she should inform the treating physician immediately. * Ability to understand and willingness to sign a written informed consent document. Exclusion Criteria: * Women who are pregnant or breast-feeding. * Subjects who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study * Subjects with previous high-dose chemotherapy with autologous allogeneic hematopoietic stem cell transplantation. * Subjects with primary brain tumors or active brain metastases are excluded. Subjects with previously treated brain metastases who are not receiving corticosteroids or anticonvulsants are eligible. * History of stroke within 6 months of treatment or other significant neurological limitations. * Use of any investigational agents within 4 weeks of study enrollment. * History of severe allergic reactions to excipients (e.g. Tween 80/polysorbate 80), including severe hypersensitivity reactions defined as greater than Grade 3 based on NCI CTC version 3. * Uncontrolled intercurrent illness including, but not limited to, human immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

NCT_ID NCT00276913

Study_NameA Phase I Study of STA-5312 in Subjects With Advanced or Metastatic Solid Tumors

Study Objectives The purpose of this trial is to evaluate 2-year disease-free survival in this patient population treated with single agent cisplatin and patients treated with cisplatin in combination with Rucaparib following preoperative chemotherapy. Side effects and tolerability of this treatment in patients with residual disease following preoperative chemotherapy will also be observed and characterized. Conditions: Breast Cancer Intervention / Treatment: DRUG: Cisplatin, DRUG: Rucaparib, DRUG: Cisplatin Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Must have histologically or cytologically confirmed triple negative (ER-/PR-/HER2-) invasive breast cancer, stage I-III at diagnosis (AJCC 6th edition) based on initial evaluation by clinical examination and/or breast imaging. NOTE: Patients with ER+ and/or PR+ may enroll ONLY if they are known carriers of a deleterious mutation in BRCA1 or BRCA2. Patients with HER2+ tumors may not enroll regardless of BRCA status. * Must have completed preoperative (neoadjuvant) chemotherapy. NOTE: Acceptable preoperative regimens include an anthracycline or a taxane, or both. Patients may NOT have received cisplatin as part of their neoadjuvant therapy regimen. Patients who received preoperative therapy as part of a clinical trial may enroll. No adjuvant chemotherapy after surgery other than that specified in this protocol is allowed. Adjuvant bisphosphonate use is allowed. * Must have completed definitive resection of primary tumor. The last surgery for breast cancer must have been completed at least 14 days prior to registration for protocol therapy. * Must have significant residual invasive disease at the time of definitive surgery following preoperative chemotherapy. Significant residual disease is defined at least one of the following: * Miller-Payne response in the breast of 0 <= age <= 25. * Residual Cancer Burden (RBC) classification II or III6 * Residual carcinoma in one or more regional lymph nodes that would meet AJCC 6th edition criteria for N1 - N3 disease. * Alternatively, if Miller-Payne or RCB grading is not available, the patient will be eligible if the pathology report indicates that the area of residual invasive disease in the breast measures at least 2 cm following preoperative therapy. The presence of DCIS without invasion does not qualify as residual disease in the breast. * Whole breast radiotherapy is required for patients who underwent breast conserving therapy, including lumpectomy or partial mastectomy. Patients receiving adjuvant radiation therapy must have completed radiotherapy at least 14 days prior to registration for protocol therapy. * Written informed consent and HIPAA authorization for release of personal health information. * Age > 18 years at the time of consent. * Must consent to allow submission of archived tumor tissue sample from definitive surgery. * Must consent to collection of blood samples for PK analysis. * Women of childbearing potential and males must be willing to use an effective method of contraception from the time consent is signed until 4 weeks after treatment discontinuation. * Women of childbearing potential must have a negative pregnancy test within 14 days prior to registration for protocol therapy. * Women must not be breastfeeding. Exclusion Criteria: * No stage IV (metastatic) disease, however no specific staging studies are required in the absence of symptoms or physical exam findings that would suggest distant disease. * No treatment with any investigational agent within 30 days prior to registration for protocol therapy. * No history of chronic hepatitis B or C * No clinically significant infections as judged by the treating investigator.

NCT_ID NCT01074970

Study_NamePARP Inhibition for Triple Negative Breast Cancer (ER-/PR-/HER2-)With BRCA1/2 Mutations

Study Objectives This is a Phase 4, open, prospective, non-interventional, multicenter trial for previously treated adult participants with relapsed/refractory follicular lymphoma (FL). Eligible participants with FL will receive 6-8 infusions of induction standard regimen of rituximab plus chemotherapy. Participants with complete or partial remission at end of induction will be assigned to maintenance therapy with rituximab once every 3 months for a maximum of 2 years or until relapse. The choice of the treatment regimen will be established on a per center basis, according to the standard in use in the country and in the center, and each center will use the same regimen through the study. Participants will be followed up for safety and efficacy evaluation in accordance with routine practice. Conditions: Lymphoma, Follicular Intervention / Treatment: DRUG: Chemotherapy, DRUG: Rituximab Location: Serbia Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Participants diagnosed with FL and had already received one or more treatments Exclusion Criteria: * Participants who are not eligible for rituximab treatment according to summary of product characteristics (SmPC)

NCT_ID NCT02472756

Study_NameA Study of Rituximab in Combination With Chemotherapy in Relapsed/Refractory Follicular Lymphoma

Study Objectives This is a randomised, double-blind, positive drug parallel controlled equivalence clinical trial initiated at about 30 sites in China. In the trial, it is planned to enroll 414 subjects, randomized to two treatment groups in a ratio of 1:1 to receive the test drug and the positive control. Conditions: Diffuse Large B-Cell Lymphoma Intervention / Treatment: DRUG: SIBP-02, DRUG: Rituximab Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * 18 <= age <= 75 years, male or female; * Patients diagnosed as CD20-positive diffuse large B-cell lymphoma after histopathological or cytological examination and untreated; * ECOG score <= 2 when enrolled; * Echocardiography measured LVEF >= 50%; * The laboratory indicators during the screening period shall meet the following criteria: White blood cell count (WBC) >= 4.0 × 109/L or the lower limit of normal of the local laboratory; patients with bone marrow invasion, WBC >= 3.0 × 109/L; Absolute neutrophil count (ANC) >= 2.0 × 109/L or the lower limit of normal of the local laboratory; in the patients with bone marrow invasion, ANC >= 1.5 × 109/L; Hemoglobin (HB) >= 90 g/L; in the patients with bone marrow invasion, HB >= 80 g/L; Platelets (PLT) >= 100 × 109/L; in the patients with bone marrow invasion, PLT >= 75 × 109/L; Total bilirubin <= 1.5 times upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 × ULN; Alkaline phosphatase <= 1.5 × ULN in the patients without bone marrow invasion; Serum creatinine level <= 1.5 × ULN; * Patients having at least one two-dimensional measurable lesion as the basis for evaluation: for intra-nodal lesions, >=1.5 cm in the long diameter and >=1.0 cm in the short diameter; for extra-nodal lesions, >=1.0 cm in the long diameter; * Patients with lymphoma International Prognostic Index (IPI) score of 0 <= age <= 2, with stage I to IV; * Female at the childbearing age who show negative in the pregnancy test, and agree to take effective contraceptive measures during the study period and within 12 months after the last dose; male patients who agree to take effective contraceptive measures during the study period and within 3 months after the last dose; * Patients with the expected survival period of greater than 6 months; * Patients voluntary to sign the Informed Consent Form. Exclusion Criteria: * Patients with primary central nervous system lymphoma and secondary central nervous system invasion, gray zone lymphoma between Burkitt and DLBCL, gray zone lymphoma between DLBCL and HL, primary mediastinal DLBCL, primary exudative lymphoma, plasmablastic lymphoma, primary skin DLBCL, ALK-positive DLBCL or transformed lymphoma; * Patients with double hit (BCL-2 and c-MYC gene rearrangement) or triple hit (BCL-2, BCL-6 and c-MYC gene rearrangement) diffuse large B-cell lymphoma diagnosed by the FISH test method; or patients with the pathological immunohistochemical test results as follows: BCL-2 >=70% positive and c-MYC>=40% positive and tumor cells judged to be the source of germinal center according to Han's evaluation criteria but without exact FISH test result; * Patients with history of malignant tumors other than cutaneous squamous cell carcinoma, cutaneous basal cell carcinoma and cervical carcinoma in situ within 5 years prior to enrollment; * Patients with major surgery (excluding diagnostic surgery) within 2 months prior to enrollment; * Patients treated for non-Hodgkin's lymphoma: Chemotherapy and immunotherapy; Radiotherapy or local radiotherapy for DLBCL; Monoclonal antibody therapy (including Rituxan® and biosimilars of Rituxan®) Surgery (except biopsy); * Patients previously receiving cytotoxic drugs or anti-CD20 antibodies to treat other diseases (e.g. rheumatoid arthritis); * Patients receiving any monoclonal antibody within 3 months prior to enrollment; * Patients who participated in other clinical trials and used other trial-related drugs within 3 months prior to enrollment; * Those vaccinated within 1 month prior to enrollment; * Those receiving hematopoietic cytokines, e.g. granulocyte colony-stimulating factor (G-CSF) within 2 weeks prior to enrollment; * Those with the maximum dose of >100mg Prednisone Acetate Tablets or equivalent cortisols for more than 5 days for the purpose of controlling lymphoma, or with the daily dose of >30mg Prednisone Acetate Tablets or equivalent cortisols for more than 10 days for the other purposes. For the patients with daily dose of <=30mg Prednisone Acetate Tablets or equivalent cortisols, there shall be written record on stable use of pre-randomization dose for at least 4 weeks; * Patients with peripheral nervous system or central nervous system disorder; * Patients with suspected active or latent tuberculosis; * Patients with known uncontrolled active bacterial, viral, fungal, mycobacterial, parasitic or other infections (excluding nail bed fungal infection) or with any significant systemic infection event that requires intravenous antibiotic treatment or hospitalization (except for neoplastic fever) within 4 weeks prior to enrollment; * HIV antibody positive; * HCV antibody positive; * HBV infection: (1) HBsAg positive, or (2) HBsAg negative, HBcAb positive and HBV DNA > 1 × 103 * Patients with complicated other diseases that might restrict the patients from participation in the clinical trial in the opinion of the investigator, including but not limited to: Cardiovascular disease: congestive heart failure (NYHA Class III-IV), unstable angina, poorly controlled arrhythmias, poorly controlled hypertension or hypotension or myocardial infarction in the past 6 months; Severe mental illness; Gastric ulcer, intestinal infarction or gastrointestinal perforation (except for ones caused by primary disease); Pulmonary diseases (asthma, interstitial lung disease or severe obstructive pulmonary disease); Poorly controlled diabetes. * Patients with contraindication to any drug in the CHOP chemotherapy regime; * Patients with allergy constitution or known to be allergic to the active ingredient, excipient or rodent product or xenogeneic protein of any drug contained in this clinical trial (including the CHOP regime); * Patients unsuitable for enrollment due to alcohol or drug abuse in the opinion of the investigator; * Female in the pregnancy or breast-feeding period; * Those unsuitable to participate in the clinical trial in the opinion of the investigator.

NCT_ID NCT04361279

Study_NameA Study Comparing SIBP-02 and Rituximab Combination With CHOP in Previously Untreated Subjects With CD20+ DLBCL

Study Objectives This is a Phase 3, multi-national, open-label, 2-arm randomized study in patients with surgically incurable metastatic melanoma who have received no prior chemotherapy, or biochemotherapy for the treatment of metastatic disease. The primary objective of this trial is to compare overall survival for patients with advanced melanoma who are randomized to receive CP-675,206 with that of patients who are randomized to receive either dacarbazine or temozolomide (investigator choice) Conditions: Melanoma Intervention / Treatment: DRUG: dacarbazine, DRUG: CP-675,206, DRUG: temozolomide Location: Poland, United Kingdom, South Africa, Australia, Austria, France, Netherlands, Greece, Canada, Slovakia, Germany, Sweden, Spain, Italy, Switzerland, Argentina, Israel, United States, Belgium, Russian Federation, Mexico Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Surgically incurable melanoma, either Stage IV or IIIC with N3 status for regional lymph nodes and in-transit or satellite lesions. * Serum lactic acid dehydrogenase (LDH) <= 2 x ULN * ECOG performance status of 0 or 1 Exclusion Criteria: * Received any systemic therapy for metastatic melanoma except post-surgical adjuvant treatment with cytokines (eg, alpha-interferon or GM-CSF) or with vaccines after complete resection of melanoma. * History of brain metastases

NCT_ID NCT00257205

Study_NameCP-675,206 Versus Either Dacarbazine Or Temozolomide In Patients Without Prior Therapy

Study Objectives PS-341 may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. Phase II trial to study the effectiveness of PS-341 in treating women who have metastatic breast cancer Conditions: Recurrent Breast Cancer, Stage IV Breast Cancer Intervention / Treatment: DRUG: bortezomib, OTHER: laboratory biomarker analysis Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed invasive breast cancer * Clinical and/or radiological evidence of stage IV disease * Relapsed or resistant disease within 6 <= age <= 12 months after completion of prior chemotherapy with doxorubicin or epirubicin and/or paclitaxel or docetaxel foradvanced disease or in the adjuvant setting * At least 1 unidimensionally measurable lesion * At least 20 mm by conventional techniques * At least 10 mm by spiral CT scan * No bone metastases as only measurable site * Pleural or peritoneal effusions not acceptable as measurable disease * No known brain metastases * Hormone receptor status: * Estrogen receptor-negative * Estrogen receptor-positive * Female * Performance status - ECOG 0 <= age <= 2 * Performance status - Karnofsky 60 <= age <= 100% * More than 12 weeks * WBC at least 3,000/mm^3 * Absolute neutrophil count at least 1,500/mm^3 * Platelet count at least 100,000/mm^3 * Bilirubin normal * AST or ALT no greater than 2.5 times upper limit of normal * Creatinine normal * Creatinine clearance at least 60 mL/min * No acute ischemia or significant conduction abnormality by EKG * No symptomatic congestive heart failure * No unstable angina pectoris * No cardiac arrhythmia * LVEF greater than 50% * No uncontrolled concurrent illness * No psychiatric illness or social situation that would preclude study * No ongoing or active infection * No prior allergic reaction(s) to compounds of similar chemical or biologic composition to PS-341 * No other malignancy within the past 5 years except carcinoma in situ of the cervix or basal cell skin cancer * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier-method contraception * See Chemotherapy * See Disease Characteristics * No more than 1 prior chemotherapy regimen for metastatic disease * High-dose regimen or bone marrow transplantation considered 1 prior regimen * At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered * Prior hormonal therapy for metastatic disease or in adjuvant setting allowed * Prior localized radiotherapy allowed if it does not influence the signal evaluable lesion * At least 4 weeks since prior radiotherapy and recovered * At least 2 weeks since prior minor surgery and recovered * At least 4 weeks since prior major surgery and recovered * No other concurrent investigational agent * No other concurrent investigational or commercial agents or therapies to treat this malignancy

NCT_ID NCT00025584

Study_NamePS-341 in Treating Women With Metastatic Breast Cancer

Study Objectives To Determine the Safety and Efficacy of Oxycodone / Naloxone Prolonged Release Tablets compared to Oxycodone PR in Subjects with Moderate to Severe, Chronic Cancer Pain Conditions: Cancer, Pain Intervention / Treatment: DRUG: Oxycodone/Naloxone, DRUG: Oxycodone Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria Males & females, at least >= 18 years with a diagnosis of cancer. Females less than one year post-menopausal must have a negative urine pregnancy test recorded prior to the first dose of study medication, be non-lactating, & willing to use adequate & highly effective method of contraception throughout the study. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently correctly such as sterilisation, implants, injectables, combined oral contraceptives, some IUDs (hormonal), sexual abstinence or vasectomised partner. Subjects who are receiving WHO step II or Step III analgesic medication who have constipation induced, or worsened by their opioid medication, as shown by * the subject's medical need of regular intake of laxatives to have at least 3 bowel evacuations per week, or having less than 3 bowel evacuations when not taking a laxative, respectively. * the subject's self-assessment that their constipation was induced or worsened by their current pre-study opioid medication. Documented history of moderate to severe, chronic cancer pain that requires around the-clock opioid therapy (starting dose of oxycodone PR between 20 <= age <= 80 mg/day) & are likely to benefit from WHO step III opioid therapy for the duration of the study. Subjects must be willing to discontinue their current opioid analgesic routine. Opioid medication continue at a stable or nearly stable dose in the investigator's opinion during the treatment. Subjects are willing to discontinue pre study laxative medication & take study specific laxative medication. Subjects taking daily fibre supplementation or bulking agents are eligible if they can be maintained on a stable dose & regimen throughout the study, & in the investigators opinion are willing & able to maintain adequate hydration. Subjects willing & able (e.g. mental & physical condition) to participate in all aspects of the study, including use of medication, completion of subjective evaluations, attending scheduled clinic visits, completing telephone contacts, & compliance with protocol requirements as evidenced by providing written, informed consent. Subjects already taking non-opioid analgesics & all other concomitant medications (including those for the treatment of depression) are eligible to take part in the study. However, all concomitant medications that are considered necessary for the subject's welfare should be continued at a stable dose throughout the double-blind phase of the study & under the supervision of the investigator. Expected survival time > 3 months. With capability of reading, understanding & signing inform consent form & compliance with protocol requirements. Exclusion Criteria Subjects that require a dose >80 mg/day oxycodone PR at the start of the double-blind phase. Any history of hypersensitivity to oxycodone, naloxone, morphine, bisacodyl, related products & other ingredients. Subjects with any situation in which opioids are contra-indicated, severe respiratory depression with hypoxia & or hypercapnia, severe chronic obstructive pulmonary disease, cor pulmonal, severe bronchial asthma, paralytic ileus. Subjects with evidence of clinically significant gastrointestinal disease (e.g. paralytic ileus, peritoneal carcinosis), significant structural abnormalities of the gastrointestinal tract (e.g. scarring, obstruction etc) either related or not related to the underlying cancer or disease progression. Evidence of clinically significant cardiovascular, renal, hepatic or psychiatric disease, as determined by medical history, clinical laboratory tests, ECG results & physical examination, that would place the subject at risk upon exposure to the study medication or that may confound the analysis & or interpretation of the study results. Abnormal aspartate aminotransferase (AST; SGOT), alanine aminotransferase (ALT; SGPT), r-glutamyltransferase (GGT) or alkaline phosphatase levels (>3 times the upper limit of normal) or an abnormal total bilirubin & or creatinine level(s) (greater than 1.5 times the upper limit of normal). Cyclic chemotherapy in the two weeks before the screening visit or planned during the core study that has shown in the past to influence bowel function. If subjects are having their first cycle of chemotherapy during the 2 weeks before the screening visit or during the double-blind phase of the study they should be excluded from the study. Radiotherapy that, in the investigators opinion, would influence bowel function or pain during the double-blind phase of the study. Subjects with known or suspected unstable brain metastases or spinal cord compression that may require changes in steroid treatment throughout the duration of the study. Subjects with uncontrolled seizures. Subjects with increased intracranial pressure. In the investigator's opinion, subjects who are receiving hypnotics or other central nervous system (CNS) depressants that may pose a risk of additional CNS depression with opioid study medication. Subjects with myxoedema, not adequately treated hypothyroidism or Addisons disease. Subjects who have a confirmed diagnosis of ongoing irritable bowel syndrome(IBS). Surgery completed within 4 weeks prior to the start of the Screening Period, or planned surgery during the study that would influence pain or bowel function during the study or preclude completion of the study. Subjects receiving opioid substitution therapy for opioid addiction (e.g. methadone or buprenorphine). Active alcohol or drug abuse & or history of opioid abuse. Subjects suffering from diarrhoea & or opioid withdrawal. Subjects presently taking, or who have taken, naloxone <=30 days prior to the start of the Screening Period. Subjects who participated in a clinical research study involving a new chemical entity or an experimental drug within 30 days of study entry (defined as the start of the Screening Period), unless the subject is on data collection phase for Overall Survival.

NCT_ID NCT01885182

Study_NameDetermine the Safety and Efficacy of Oxy/Nal Tablets Compared to Oxy PR in Subjects With Cancer Pain

Study Objectives This randomized study will assess the efficacy and safety of the combination of Pivanex and docetaxel compared to docetaxel alone in patients with a type of lung cancer called non-small cell lung cancer. Pivanex is an investigational agent, and docetaxel is an approved drug. Conditions: Carcinoma, Non-Small-Cell Lung Intervention / Treatment: DRUG: Pivanex, DRUG: Docetaxel Location: United Kingdom, United States, India Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed non-small cell lung cancer (NSCLC); Treatment with one prior platinum-based chemotherapy regimen (Eligible patients may include: 1. Patients previously treated with adjuvant or neoadjuvant chemotherapy (must be completed within 6 months prior to randomization) or 2. Patients who have received chemotherapy for advanced or metastatic lung cancer); * Recurrent or progressive NSCLC (local, distant, or both) following initial chemotherapy); * Measurable or non-measurable disease; * Males and females, age => 18 years; * Adequate renal function with creatinine => 1.5 mg/dl; * Adequate liver function with alkaline phosphatase => 2.5 X upper limit of normal, SGOT, and SGPT => 1.5 X upper limit of normal; and total bilirubin => upper limit of normal; * Adequate bone marrow function: platelets > 100,000/mm3, hemoglobin => 9 g/dL, and absolute neutrophil count (ANC) => 1,500 cells/mm3; * Able to give informed consent; * Discontinuation of previous surgery, radiation therapy or cancer chemotherapy at least four weeks prior to randomization (six weeks if a prior nitrosourea or mitomycin C), with recovery from treatment-associated toxicity; * A predicted life expectancy of at least 12 weeks; and * ECOG performance status of 0, 1, or 2. Exclusion Criteria: * Receipt of more than one chemotherapy regimen for NSCLC; * A second malignancy within the last 5 years other than curatively treated carcinoma-in-situ or non-melanoma skin cancer; * Pregnant or lactating females (Females of childbearing potential must have a negative pregnancy test and all male and female patients of reproductive potential must agree to use adequate birth control); * Known HIV-positive patients; * Acute medical problems, such as ischemic heart or lung disease or uncontrolled systemic infection; * Patients with any underlying medical conditions or circumstance, which would contraindicate therapy with study treatment, affect compliance or impair evaluation of study endpoints; * Patients receiving investigational agents within 30 days of the screening visit; * Known allergy to reagents in the study; * Prior docetaxel therapy; * Symptomatic or untreated brain metastases (Patients with brain metastases are eligible if they are clinically and neurologically stable for > 4 weeks since therapy (radiation therapy, radiosurgery/gamma knife; surgical resection) as determined by the investigator and either off corticosteroids or on a stable dose of corticosteroids).

NCT_ID NCT00073385

Study_NameComparative Trial of Pivanex and Docetaxel Vs Docetaxel Monotherapy in Patients With Advanced Non-Small Cell Lung Cancer

Study Objectives This is a multi center, open-label study to evaluate the drug-drug interaction of LDE225 on the PK of bupropion and warfarin patients with advanced solid tumors. Subjects will receive 800mg daily of LDE225 and two separate doses of either bupropion or warfarin. Conditions: Advanced Solid Tumor Intervention / Treatment: DRUG: LDE225, DRUG: Wafarin, DRUG: Bupropion Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Adults * Patients with cytopathologically or histopathologically confirmed diagnosis of an advanced solid tumor which has progressed despite standard therapy, or for which no standard therapy exists or patients with locally advanced or metastatic basal cell carcinoma who are not amendable or eligible for standard therapy. * Protocol-defined renal , liver and bone marrow function Exclusion Criteria: * CNS (Central Nervous System) tumors as well as history of brain metastases * Systemic anticancer treatment (including biologic therapy/antibodies) within 2 weeks before first dose of study treatment (6 weeks for nitrosourea, mitomycin, and monoclonal antibodies). * Radiation therapy within 4 weeks before first dose * Investigational agents within 4 weeks before start of study therapy * Patients with known allergy/hypersensitivity to warfarin or bupropion and/or related compounds * Patients with a history of/or active bleeding disorders * Patients receiving treatment with vitamin K, Coumadin or other agents containing warfarin and heparin. Heparin flush to maintain patency of a central venous access device is allowed. * Patients receiving treatment with bupropion. * Patients who have neuromuscular disorders that are associated with elevated CK (Creatine phosphokinase) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy). * Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B or C (testing is not mandatory for study entry) * Patients currently receiving systemic corticosteroids Other protocol-defined inclusion/exclusion criteria may apply

NCT_ID NCT01769768

Study_NamePhase I Study to Evaluate the Effect of LDE225 on the Pharmacokinetics of Bupropion and Warfarin in Patients

Study Objectives Estrogen is known to be a regulator of bone and lipid metabolism. Letrozole is a potent inhibitor of estrogen synthesis. This study evaluated the effects of letrozole and tamoxifen on bone and lipid metabolism in postmenopausal women with resected, receptor positive early breast cancer. Conditions: Hormone Sensitive Resected Primary Breast Cancer in Postmenopausal Women Intervention / Treatment: DRUG: Letrozole, DRUG: Tamoxifen Location: Denmark, United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria * Female * Post-menopausal hormone status defined as: * Patients with menostasis (amenorrhea) > 12 months or history of oophorectomy. * Patients >= 55 years with history of hysterectomy or having continued/renewed menstruation on cyclic hormone treatment. * Patients of 50 <= age <= 54 years: Menopausal status was determined on the basis of follicle-stimulating hormone (FSH)/luteinizing hormone (LH) values. * Histologically confirmed resected breast cancer and eligible for adjuvant endocrine therapy. As a minimum, patients had to have receptor-positive tumors, which were defined either as estrogen receptor (ER) and/or progesterone receptor (PgR) >= 10 fmol/mg cytosol protein; or >= 10% of the tumor cells positive by immunocytochemical evaluation. * Adequate bone marrow function (white blood cell count [WBC] > 3.0 x 109 /L, platelets >= 100.0 x 109 /L, and hemoglobin > 10 g/dL). * Documented evidence of adequate renal function (creatinine < 180 µmol/L) and hepatic function (bilirubin < 30 µmol/L, alanine aminotransferase (ALT) < 1.5 x upper normal limit of the laboratory). * Life expectancy of at least 24 months at the time of enrollment. * Written voluntary informed consent prior to initiation of any study procedure. * Willingness to undergo all scheduled tests and examinations for evaluation of bone density and bone metabolism, and lipid profiles in addition to the standard assessments for monitoring their breast cancer status. Exclusion Criteria * Patients with distant metastases as defined by the criteria of the Danish Breast Cancer Co-operative Group (DBCCOG). * Pre-existing bone disease (e.g. osteomalacia, osteogenesis imperfecta, Paget's disease). * Patients receiving bisphosphonates for more than 3 months before randomization. * Chronic treatment with drugs known to interfere with bone metabolism, e.g. * Anti-convulsants within the past year. * Corticosteroids at doses greater than the equivalent of 5 mg/day prednisone for more than two weeks in the past 6 months (prior to randomization). * Any previous treatment with sodium fluoride at daily doses >= 5 mg/day for a period exceeding 1 month. * Anabolic steroids in the past 12 months. * Long term use of coumarin derivatives and heparin at the time of randomization. * Metabolic diseases known to interfere with bone metabolism (e.g., Hyperparathyroidism, hypoparathyroidism, uncontrolled thyroid disease, Cushing's disease, vitamin D deficiency, malabsorption syndrome, etc.). * Treatment with lipid-lowering agents within the 3 months prior to randomization (this exclusion criterion did not apply to patients randomized in the United Kingdom). * Patients receiving other anti-cancer treatment. * Previous neoadjuvant / adjuvant chemotherapy and /or previous adjuvant endocrine therapy (e.g., anti-estrogens, AIs). * History of previous or concomitant malignancy within the past 5 years other than adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Patients who had a previous other malignancy must have been disease free for five years. Patients with endometrial cancer and/or invasive breast cancer at any time in their medical history were excluded. Patients with invasive bilateral breast cancer were excluded. Patients with vaginal discharge/ vaginal bleeding with evidence of malignancy were excluded. * Any other non-malignant systemic diseases (cardiovascular, renal, hepatic, lung embolism, etc.) which would prevent prolonged follow-up.

NCT_ID NCT00171704

Study_NameA Study to Evaluate the Effect of Letrozole and Tamoxifen on Bone and Lipids in Postmenopausal Women With Breast Cancer

Study Objectives This open-label, multicenter, global study is designed to assess the safety, tolerability, preliminary efficacy, and pharmacokinetics of intravenous atezolizumab (MPDL3280A) and obinutuzumab in participants with refractory or relapsed follicular lymphoma (FL) or atezolizumab and obinutuzumab or tazemetostat administered in participants with refractory or relapsed diffuse large B-cell lymphoma (DLBCL). The anticipated duration of this study is approximately 4.5 years. Conditions: Lymphoma Intervention / Treatment: DRUG: Atezolizumab, DRUG: Obinutuzumab, DRUG: Tazemetostat Location: Germany, United Kingdom, United States, Italy, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically documented, CD20-positive, relapsed or refractory (defined as having relapsed within 6 months to the previous treatment) FL or DLBCL (including primary mediastinal large B-cell lymphoma [PMLBCL]) * Bone marrow biopsy at screening (unless it was performed within 3 months prior to screening) * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 * Life expectancy greater than or equal to (>=) 12 weeks * Has a QT interval corrected by Fridericia's formula (QTcF) less than or equal to (<=) 480 milliseconds (msec) * At least one bi-dimensionally measurable nodal lesion >1.5 cm in its longest diameter by computed tomography (CT) scan or MRI, as defined by the Lugano Classification * Adequate hematologic and end-organ function * Archival tumor tissue * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 90 days after the last dose of atezolizumab or 18 months after the last dose of obinutuzumab, whichever is longer * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm Exclusion Criteria: * Known central nervous system lymphoma, leptomeningeal lymphoma, or histologic evidence of transformation from an indolent lymphoma to a high-grade or DLBCL * Grade 3b FL, small lymphocytic lymphoma (SLL), or Waldenström's macroglobulinemia (WM) or other lymphoma subtypes except as stated in the inclusion criteria * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently); participants with indwelling catheters are eligible * Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab * History of severe allergic or anaphylactic reactions to monoclonal antibody therapy * Has had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homolog 2 (EZH2) * Regular treatment with corticosteroids within the 2 or 4 weeks prior to the start of Cycle 1, unless administered for indications other than non-Hodgkin's lymphoma at a dose equivalent to < 30 mg/day prednisone/prednisolone * Pregnant and lactating women * History of autoimmune disease * Participants with history of confirmed progressive multifocal leukoencephalopathy (PML) * Participants with prior allogeneic bone marrow transplantation or prior solid organ transplantation * History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis per chest CT scan at screening. History of radiation pneumonitis in the radiation field (fibrosis) is allowed * Positive test for Human Immunodeficiency Virus (HIV) * History of chronic hepatitis B infection or positive test results for active or chronic hepatitis B or hepatitis C * Significant cardiovascular disease, such as cardiac disease (New York Heart Association Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina * Hypersensitivity or prior treatment with obinutuzumab * Fludarabine or Campath within 12 months prior to study entry * Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA4, anti-PD-1, and anti-PD-L1 therapeutic antibodies * Treatment with systemic immunostimulatory agents (including but not limited to interferon, interleukin-2) within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1 * Treatment with systemic immunosuppressive medications, including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (anti-TNF) agents within 2 weeks prior to Cycle 1, Day 1; inhaled corticosteroids and mineralocorticoids are allowed * Participants with active tuberculosis (TB) will be excluded from the clinical trial

NCT_ID NCT02220842

Study_NameA Safety and Pharmacology Study of Atezolizumab (MPDL3280A) Administered With Obinutuzumab or Tazemetostat in Participants With Relapsed/Refractory Follicular Lymphoma and Diffuse Large B-cell Lymphoma

Study Objectives The purpose of this study is to determine whether treatment with Selumetinib (AZD6244) (Hyd-Sulfate) in combination with Irinotecan as a second treatment in patients with K-ras or B-raf mutation will prevent tumor progression and prolong progression free survival. Conditions: Colorectal Cancer Intervention / Treatment: DRUG: AZD6244, DRUG: Irinotecan Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histological or cytological confirmation of advanced or metastatic colorectal cancer with available tissue and tumor sample confirmed as K-ras or B-raf mutation positive. Current failure of 1st line anti-cancer therapy with an oxaliplatin and bevacizumab based regimen or patients relapsing within 12 months of completing adjuvant FOLFOX . Exclusion Criteria: * Treatment within 14 days prior to first study treatment with conventional therapy or treatment within 28 days prior to first study treatment with an investigational drug Prior treatment with a MEK or B-raf inhibitor or any irinotecan-containing regimen Prior treatment with a MEK or B-raf inhibitor or any irinotecan-containing regimen

NCT_ID NCT01116271

Study_NameStudy of Selumetinib (AZD6244)(ARRY-142886) in Combination With Irinotecan in Previously Treated Patients With Colorec

Study Objectives The purpose of this study is in non small-cell lung cancer stage IV et IIIB (T4 with pleural effusion) in elderly dependent patients with evaluation of the sequence Gemcitabine first line followed by Erlotinib when progression versus Erlotinib first line followed by Gemcitabine when progression Conditions: Non Small Cell Lung Cancer Intervention / Treatment: DRUG: TARCEVA, DRUG: Gemzar Location: France Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Age > 65 * Comorbidities score, PS and frailty score according to table 1 * No dementia, faecal or urinary incontinence, repeated falls * ADL = 0, IADL = 0 <= age <= 1 * Life expectancy at least 12 weeks * Creatinin clearance > = 30 ml/mn (according to Cockcrofts-Gault formula) * Competency to give written informed consent * Haematological functions as follows : neutrophiles count > 1.5 x 109/l and platelets > 100 x 109/l hemoglobin > 9,5 g/dl - Hepatic function as follows : Bilirubin < 1,25 LNS ASAT / ALAT <5 x NAlcPh <5 x N * PS < 3 * cerebral metastasis eligible if asymptomatic * Histologically or cytologically confirmed NSCLC * Stage IV/IIIB4 (T4 with pleural effusion) * No prior chemotherapy * relapses of previous NSCLC treated by surgery or radiotherapy are eligible, if the target is measurable out of initial radiotherapy field and if cytological or histological proof * At least one measurable target lesion by RECIST guidelines Exclusion Criteria: * symptomatic cerebral metastasis * Any severe comorbidity calculated by Charlson score according to table 1 * ADL > 0 and IADL > 1- performance status >2 (ECOG) * peripheral neuropathy grade 2 or more * dementia, repeated falls, urinary or faecal incontinence * contra-indication to corticosteroids * contra indication to a product of this study * unwilling or unable to comply with study requirements, for personal, family, sociologic, geographic or any other reason * inability of the subject to give written informed consent * lack of liberty following legal or administrative decision * hypersensitivity to polysorbate * hypersensitivity to erlotinib or any excipients of this product * unusual hereditary disorders, as galactosemia, deficit in lactase and syndrome of malabsorption in glucose or galactose * participation in concomitant clinical trial * bronchioloalveolar or neuroendocrine or composite carcinoma * superior vena cava syndrome

NCT_ID NCT00419042

Study_NameElderly Dependent Patients With Non Small Cell Lung Cancer (NSCLC)

Study Objectives This is an open-label, non-randomized, multi-center, phase II trial of brentuximab vedotin to evaluate ORR primarily in patients with EBV- and CD30-positive lymphomas. Conditions: Relapsed or Refractory EBV-and CD30-positive Lymphomas Intervention / Treatment: DRUG: brentuximab vedotin Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with relapsed or refractory EBV- and CD30-positive lymphomas * Age >= 18 years * ECOG performance status 0 <= age <= 2 * At least one measurable lesion based on revised Cheson's or modified SWAT criteria * Provision archival tumor tissues (4 μm thickness x 5 unstained slides) and blood samples * Voluntary written informed consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care. * Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse. * Male patients, even if surgically sterilized, (i.e., status post vasectomy) agree to practice effective barrier contraception during the entire study period and through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse. * Adequate hematologic function: absolute neutrophil count (ANC) >=1,500/µL, platelet count >= 75,000/µL, and hemoglobin >=8.0 g/dL unless there is known hematologic tumor marrow involvement (ANC >= 1,000/µL and platelet count >= 50,000/µL if there is known bone marrow involvement) * Adequate liver function: total bilirubin < 1.5 x the upper limit of the normal (ULN) unless the elevation is known to be due to Gilbert syndrome and ALT or AST < 3 x ULN (AST and AST < 5 x ULN if their elevation can be reasonably ascribed to the presence of hematologic tumor in liver) * Adequate renal function: serum creatinine < 2.0 mg/dL and/or creatinine clearance or calculated creatinine clearance > 40 mL/minute. * Expected survival > 3 months Exclusion Criteria: * Female patient who are both lactating and breast-feeding or have a positive serum pregnancy test * Any serious medical or psychiatric illness * Known cerebral or meningeal involvement (EBV- and CD30-positive lymphoma or any other etiology), including signs or symptoms of PML * Symptomatic neurologic disease compromising normal activities or requiring medication * Any sensory or motor peripheral neuropathy greater than or equal to Grade 2 * Known history of myocardial infarction within 1 year, NYHA class III/IV heart failure, or uncontrolled cardiovascular conditions including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Recent evidence (within 6 months before first dose of study drug) of a left-ventricular ejection fraction <50%. * Any active systemic viral, bacterial, or fungal infection within 2 weeks prior to first study drug dose * Any prior chemotherapy and/or other investigational agents within at least 5 half-lives of last dose * Prior stem cell transplantation within 100 days or radioimmunotherapy within 8 weeks * Prior exposure to CD30-targeted agents * Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin * Known human immunodeficiency virus (HIV) positive * Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection * Another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.

NCT_ID NCT02388490

Study_NameBrentuximab Vedotin in Patients With Relapsed or Refractory EBV-and CD30-positive Lymphomas

Study Objectives The primary objective of Part I of the study is to determine tumor response rate of sequential topoisomerase targeting with irinotecan/oxaliplatin followed by etoposide /carboplatin in chemotherapy-naïve patients with extensive small cell lung cancer. The primary objective of Part II of the study is to determine the objective tumor response rate of irinotecan/oxaliplatin in patients with either refractory disease or who have relapsed to first line chemotherapy or chemoradiotherapy. Conditions: Non-Small Cell Lung Cancer Intervention / Treatment: DRUG: Intervention A: Irinotecan; Oxaliplatin; Neulasta, DRUG: Intervention B: Etoposide; Carboplatin; Neulasta Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologic or cytologic diagnosis of SCLC. * Measurable or assessable tumor parameters. * Eastern Cooperative Oncology Group (ECOG) Performance Status 0 <= age <= 2. * Age between 18 and 79 years (in the State of Alabama > 18). * Adequate bone marrow, liver and renal function, defined as: * Absolute neutrophil count (ANC) >= 1500/µL * Platelet count >= 100,000/µL * SGOT/SGPT <= 2.5 x upper limit of normal or <= 5 x upper limit of normal when liver metastases are present. * Total bilirubin value <= 1.5 x upper limit of normal. * Serum creatinine value <= 1.5 x upper limit of normal. * Fully recovered from any previous surgery (at least 4 weeks since major surgery) * Must have recovered from prior radiation therapy (at least 3 weeks) * All participants must agree to practice approved methods of birth control (if applicable). A negative pregnancy test must be documented during the screening period for women of childbearing potential. * Must provide written informed consent and authorization to use and disclose health information (HIPAA). For Part I * Extensive-stage SCLC as defined as disease not confined to one hemithorax, including ipsilateral pleural effusion or pericardial effusion. * No prior chemotherapy. For Part II * Patients with either refractory disease, or who have relapsed 1st line therapy. No prior chemotherapy with Oxaliplatin or irinotecan. * Demonstrated tumor progression at the time of study entry. Exclusion Criteria: * Concurrent cancer chemotherapy, biologic therapy or radiotherapy. * Administration of any investigational drug within 28 days prior to administration of the current therapy. * Symptomatic brain metastases; those patients should be treated first with either whole brain radiation therapy or radiosurgery. * Concurrent serious infection. * Concomitant severe or uncontrolled underlying medical disease unrelated to the tumor, which is likely to compromise patient safety and affect the outcome of the study. * History of other malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for a minimum of 2 years. * Neuropathy at baseline >= Grade 2. * Any evidence or history of hypersensitivity or other contraindications for the drugs used in this trial. * History of chronic diarrhea; or diarrhea (excess of 2 <= age <= 3 stools/day above normal frequency) in the past 2 weeks. * History of a positive serology for human immunodeficiency virus (HIV). * Psychiatric disorder that prevents patients from providing informed consent or following protocol instructions. * Pregnant or lactating women.

NCT_ID NCT00240097

Study_NameStudy of Sequential Topoisomerase, Irinotecan/Oxaliplatin - Etoposide /Carboplatin in Extensive Small Cell Lung Cancer (SCLC)

Study Objectives RATIONALE: Drugs used in chemotherapy, such as epirubicin, oxaliplatin, fluorouracil, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy and radiation therapy after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase II trial is studying how well giving combination chemotherapy, surgery, and radiation therapy works in treating patients with locoregionally advanced cancer of the esophagus, gastroesophageal junction, or stomach. Conditions: Esophageal Cancer, Gastric Cancer Intervention / Treatment: DRUG: cisplatin, DRUG: epirubicin hydrochloride, DRUG: fluorouracil, DRUG: oxaliplatin, PROCEDURE: adjuvant therapy, PROCEDURE: neoadjuvant therapy Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must have a histologic diagnosis of adenocarcinoma of the esophagus, gastroesophageal junction or gastric cardia, based on biopsy material or adequate cytologic exam. * Patients must be clinically staged according to the AJCC 2002 staging system and must have either T3 <= age <= 4, or N1 or M1a disease. Staging should include at least an upper endoscopy with endoscopic ultrasound and an FDG-PET/CT scan. * Patients must have an ECOG performance status of 0 <= age <= 1. * Patients must have adequate bone marrow function as evidenced by: Absolute neutrophil count > 1,500/uL Platelet count > 100,000/uL * Patients must have adequate renal function as evidenced by serum creatinine < 1.6 mg/dL * Patients must have adequate hepatic function as evidenced by:Serum total bilirubin < 1.5 mg/dL Alkaline phosphatase < 3X the institutional ULN AST/ALT < 3X the institutional ULN * Patients must have adequate pulmonary function as evidenced by an FEV1 > 50% predicted. * Patients or their legal representatives must be able to read, understand, provide and sign informed consent to participate in the trial. * Patients of childbearing potential agree to use an effective form of contraception during the study and for 90 days following the last dose of study medication (an effective form of contraception is an oral contraceptive or a double barrier method) * Age > 18 years Exclusion Criteria: * Patients with any other diagnosis except for adenocarcinoma (squamous cell carcinoma, small cell carcinoma, mixed adenosquamous, lymphoma, sarcoma etc,) will be ineligible. * Patients with any evidence of distant hematogenous or distant nodal disease (M1b) will be ineligible. * No prior chemotherapy, radiation therapy or surgery for this malignancy will be allowed. Prior endoscopic debulking, laser therapy or dilatation will not exclude a patient. * Patients with another active malignancy will not be eligible except for curatively treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized prostate cancer with a current PSA of < 1.0 mg/dL on 2 successive evaluations at least 3 months apart, with the most recent evaluation within 4 weeks of entry * Patients with an active infection will not be eligible. * Patients with known hypersensitivity to any of the components of oxaliplatin, epirubicin, fluorouracil or cisplatin will not be eligible. * Patients who are receiving any other concurrent investigational therapy, or who have received investigational therapy within 30 days of the first scheduled day of protocol treatment (investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication) will not be eligible. * Patients with a baseline peripheral neuropathy greater than or equal Grade 2 will not be eligible. * Patients who are pregnant or lactating will not be eligible. * Patients with any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results, will not be eligible. * Patients with any history of an allogeneic transplant will not be eligible. * Patients with known infection with HIV, Hepatitis B or C (active, previously treated or both) will not be eligible.

NCT_ID NCT00601705

Study_NameEpirubicin, Oxaliplatin and Fluorouracil (EOF) in Cancer of the Esophagus, Gastroesophageal Junction, or Stomach

Study Objectives The purpose of this study is to evaluate the effect of the anti-programmed death 1 (PD-1) agent nivolumab following selective internal radiation therapy (SIRT) for patients with unresectable hepatocellular carcinoma (HCC). SIRT using yttrium90-loaded microspheres is increasingly used to treat patients with HCC, particularly those that are not good candidates for transarterial chemoembolization or TACE. SIRT induces disease control (objective tumor remission or stabilization) in most patients while progression usually results from the growth of new lesions. SIR-Spheres are resin-made microspheres used for SIRT. On the other hand, nivolumab is under clinical development for the treatment of more advanced HCC. Available data in patients that mostly had progression to other therapies and vascular involvement or metastatic disease show significant systemic antitumor activity that results in durable objective remissions and disease stabilizations. Therefore, in patients with HCC that has not spread beyond the liver, the systemic action of nivolumab may improve the anti-tumor effect of SIRT. Furthermore, by inducing immunogenic tumor cell death, SIRT may have a synergistic effect with nivolumab. Conditions: Hepatocellular Carcinoma Intervention / Treatment: DRUG: Nivolumab, DEVICE: SIR-Spheres Location: Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Diagnosis of HCC based on histology or non-invasive criteria if cirrhotics. Patients with fibrolamellar carcinoma are not excluded. * Cirrhosis absent, non-viral or due to hepatitis C or B virus infection. Subjects with chronic hepatitis B virus infection must be on effective antiviral therapy * Preserved liver function (without cirrhosis or with compensated cirrhosis in Child Pugh Class A). * ECOG performance status 0 or 1 * Willing to have a liver biopsy pre-treatment * Considered candidates for locoregional therapy using SIR-Spheres based on * the absence of extrahepatic disease (patients with regional lymph nodes < 2 cm in short axis are accepted) * unsuitability for liver resection or transplantation, or percutaneous ablation * considered not good candidates for TACE because they have; Single tumors larger than 5 cm. Multiple tumors that cannot be targeted superselectively. Unilobar tumors with segmental or lobar portal vein thrombosis. * At least one measurable lesion by RECIST 1.1 criteria. * Adequate organ and marrow function as evidenced by: * White blood cell count >= 2000/μL. * Neutrophils >= 1000/μL. * Platelets >= 60 x 103/μL. * Hemoglobin >= 9.0 g/dL. * Creatinine Clearance > 40 mL/min. * AST and ALT <= 5 X ULN * Bilirubin <= 2 mg/dL * INR <= 1.8. * Albumin >= 3.0 g/dL * Willing and able to comply with immune-monitoring sample collection and required study follow-up. Exclusion Criteria: * Any history of hepatic encephalopathy * Any prior (within 6 months) or current clinical ascites. * Any history of clinically meaningful variceal bleeding within the last three months. * Active coinfection with both hepatitis B and C or hepatitis D infection in subjects with hepatitis B * Occlusive main trunk portal vein thrombosis or absence of intrahepatic portal blood flow if patient carries a portocaval shunt. * Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured. * Any autoimmune disease that may require immunosuppressive therapy. * Any severe organ disease * Prior therapy with any drug specifically targeting T-cell costimulation or checkpoint pathways. * Prior organ allograft or allogeneic bone marrow transplantation * Active bacterial or fungal infections within 7 days of study entry. * Any condition requiring systemic treatment with corticosteroids or other immunosuppressive medications within 14 days of study drug administration.

NCT_ID NCT03380130

Study_NameA Study of the Safety and Antitumoral Efficacy of Nivolumab After SIRT for the Treatment of Patients With HCC

Study Objectives The purpose of this study is to determine the safety and effectiveness of the combination of docetaxel and ZD1839 on destroying prostate cancer before removal of the prostate. Conditions: Prostate Cancer Intervention / Treatment: DRUG: docetaxel, DRUG: ZD1839 Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * prostate carcinoma: clinical stage T2b-3 or serum PSA>20 ng/ml or Gleason sum score 8 <= age <= 10. * clinical T2 patients are eligible if endorectal coil MRI shows T3 disease, or Gleason 4+3 cancer in 5 or more biopsies (minimum of 10 biopsies total required) * ECOG performance status of 0, 1 or 2 * adequate hematological, liver and renal function * existing peripheral neuropathy < grade 1 * ability to tolerate oral medications. Exclusion Criteria: * Concurrent or prior treatment with radiation, cytotoxic, biologic therapy for prostate cancer * any major surgery within four weeks * prior hormonal therapy (except finasteride for obstructive voiding symptoms- -evidence of metastatic disease, confirmed by physical examination, computed tomography of the abdomen and pelvis within 45 days and by bone scan within 60 days of signing informed consent

NCT_ID NCT00242918

Study_NameSafety and Effectiveness Study of Docetaxel and ZD1839 Followed by Removal of the Prostate to Treat Prostate Cancer

Study Objectives The trial is a study conducted to evaluate the safety, tolerability and PK characteristics of Carrimycin tablet and measure its anti-tumor efficacy initially in the treatment of patients with locally advanced, recurrent, or metastatic head and neck squamous cell carcinoma (non NPC). Conditions: Oral Squamous Cell Carcinoma, Head and Neck Squamous Cell Carcinoma Intervention / Treatment: DRUG: Carrimycin Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Locally advanced, recurrent, or metastatic head and neck squamous cell carcinoma (non NPC) confirmed by histopathological or cytological diagnosis * Expected life expectancy is no less than 6 months; * ECOG PS is 0, 1 or 2; * Subjects should be enrolled at least 4 weeks after the lastest treatment of surgery, radiotherapy, chemotherapy, or biotherapy, etc. * The laboratory inspection indexes should meet the following requirements: Leukocyte>3×109/L, Neutrophils>1.5×109/L, Platelet count>75×109/L，Hemoglobin>80g/L, Serum total bilirubin<1.5ULN, ALT or AST<2.5ULN, Creatinine<2.0ULN, BUN<2.0ULN, Maximum extension of APTT normal is within 10s, Maximum extension of PT normal is within 3s. * Women of reproductive age (18 <= age <= 45 years) must have a negative urine pregnancy test and agree to receive effective contraception. Male subjects must voluntarily receive appropriate contraception. Exclusion Criteria: * There is still any undiminished CTCAE grade 2 or higher toxicity from previous anti-cancer treatments; * There are significant cardiovascular abnormalities (e.g. myocardial infarction, upper-cavity venous syndrome, heart disease of grade 2 or higher diagnosed according to the New York Heart Association (NYHA) classification criteria 3 months prior to enrollment); * There is active severe clinical infection (>NCI-CTCAE V5.0 Level 2) * Urine routine shows albuminuria >= ++, but if albuminuria at baseline >= ++, patients with albuminuria /24h<1g measured quantitatively based on 24-hour urine collection can be enrolled; * Allergic to macrolides; * Uncontrolled hypertension (systolic > 150 mmHg and / or diastolic >100mmHg) or clinically significant (e.g. active) cardiovascular diseases - such as stroke (<= 6 months before randomization), myocardial infarction (<= 6 months before randomization), unstable angina pectoris, congestive heart failure of New York Heart Association (NYHA) functional class III or above, or serious arrhythmia that cannot be controlled with drugs or has potential impact on trial treatment. * Known to have acute or chronic active HBV or HCV infection and need antiviral treatment with non nucleoside drugs; * Women pregnant or lactation; * Having participated in other clinical studies and received any other investigational drug for treatment within 30 days before enrollment; * Having taken macrolide antibiotics (azithromycin, erythromycin, roxithromycin, clarithromycin, dirithromycin, spiramycin, acetylspiramycin, midecamycin, rokitamycin, meleumycin, josamycin, leucomycin, miocamycin) within 3 days before enrollment; * Other cases considered inappropriate by the investigator to participate in the study.

NCT_ID NCT04413214

Study_NameCarrimycin in Patients With Locally Advanced, Recurrent, or Metastatic HNSCC (Non NPC): A Phase I Trial

Study Objectives The aim of this study is to determine the maximal tolerated dose level of lenalidomide combined with fludarabine/rituximab in the therapy of patients with previously untreated CD20-positive chronic lymphocytic leukemia. Following a dose escalation phase lenalidomide will be given at the pre-determined maximum tolerated dose in combination with rituximab to further determine the efficacy and tolerability of this regimen. Conditions: Leukemia, Lymphocytic, Chronic, B-Cell Intervention / Treatment: DRUG: Lenalidomide, DRUG: Fludarabine, BIOLOGICAL: Rituximab Location: Austria Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * B-CLL (CD23+, CD5+, CD19+, CD20+) * Treatment indication according to NCI criteria * Age >= 18 yrs * No previous treatment of CLL by chemo-, radio- or immunotherapy * Life expectancy > 6 months * Written informed consent * Women of non-childbearing potential or women of childbearing potential and men using effective contraception Exclusion Criteria: * Active bacterial, viral or fungal infection * Positivity for HIV, Hepatitis B or C * Reduce organ functions and bone marrow dysfunction not due to CLL * Creatinine clearance below 30 ml/min * Patients with medical conditions requiring long-term use of systemic corticosteroids during study treatment * Patients with a history of severe cardiac disease * Other known co-morbidity with the potential to dominate survival * Transformation to aggressive B-cell malignancy * Known hypersensitivity to humanised monoclonal antibodies or any of the study drugs * Pregnant or breast-feeding women * Any co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent

NCT_ID NCT00738829

Study_NameLenalidomide Dose Escalation Combined With Rituximab/Fludarabine in Untreated CLL

Study Objectives This phase I/II trial studies the side effects and best dose of tivozanib and to see how well it works in treating patients with liver cancer that has spread to other parts of the body or cannot be removed by surgery. Tivozanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Conditions: Advanced Adult Hepatocellular Carcinoma, Non-Resectable Hepatocellular Carcinoma Intervention / Treatment: DRUG: Tivozanib (1mg), DRUG: Tivozanib (1.5mg) Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: * Advanced staged HCC (unresectable and not amenable to local or regional therapy; or metastatic HCC); the diagnosis of HCC should be based on at least one of the following: * Magnetic resonance imaging (MRI) or computed tomography (CT) consistent with liver cirrhosis AND at least one solid liver lesion measuring >= 2 cm, with characteristics arterial enhancement and venous washout regardless of alpha-fetoprotein (AFP) levels * AFP >= 400 ng/mL AND evidence of at least one solid liver lesion >= 2 cm regardless of specific imaging characteristics on CT or MRI * Histological/cytology biopsy confirming HCC * Patients must have measurable disease per RECIST 1.1 criteria defined as at least one lesion that can be accurately measured in at least one dimension, and that has not been the target of local or regional therapy including transarterial chemoembolization, intra-arterial chemotherapy, ethanol or radiofrequency ablation * Life expectancy of greater than 3 months * Child-Pugh liver function class A * Aspartate aminotransferase (AST) =< 5 x institutional upper limits of normal (ULN) * Total bilirubin =< 3 mg/dL * International normalized ratio (INR) =< 2.0 (unless due to therapeutic warfarin use) * Serum albumin > 2.8 g/dL * Creatinine =< 1.5 x institutional ULN * Absolute neutrophil count (ANC) >= 1200/mm^3 * Platelets >= 60,000/mm^3 * Hemoglobin (Hgb) >= 8.5 g/dL * Patients must not have any evidence of bleeding diathesis or active gastrointestinal bleeding * Patients must not be known to be human immunodeficiency virus (HIV) positive * Patients must not have other uncontrolled intercurrent illnesses (excluding HBV or HCV); this includes (but is not limited to) ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Sexually active fertile patients (male and female), and their partners, must agree to use medically accepted methods of contraception during the course of the study and for 3 months after the last dose of the study drug * Female patients of childbearing potential must have a negative pregnancy test at screening * Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 * Subject or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: * Patients who have had prior anti-angiogenic therapy, including but not limited to sorafenib, brivanib, bevacizumab, or sunitinib * Patients who have had any prior line of systemic therapy including cytotoxic agents or molecularly targeted agents for advanced/unresectable disease; any number of prior regional therapies with transarterial chemoembolization (TACE), brachytherapy with yttrium-90 microsphere, intra-arterial chemotherapy, surgery, or ablative therapy are allowed * Prior liver transplantation and on immunosuppression * Known symptomatic or uncontrolled brain metastases or epidural disease * Patient has a corrected QT interval (QTcF) > 500 ms at screening * The patient is unable to swallow pills or diagnosed with a gastrointestinal disorder that are likely to interfere with the absorption of the study drug or with the patient's ability to take regular oral medication * The patient is pregnant or breastfeeding * Patients with second primary cancer (except adequately treated nonmelanoma skin cancer, curatively treated in-situ carcinoma of the cervix or superficial bladder cancer, or other solid tumors including lymphoma without bone marrow involvement curatively treated with no evidence of disease for >= 5 years) * The patient has a previously-identified allergy or hypersensitivity to components of the study treatment formulation * Patients receiving any medications or substances that are strong inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible; moderate inducers of CYP3A4 should be used with caution * Urine protein: creatinine ratio > 1

NCT_ID NCT01835223

Study_NameTivozanib in Treating Patients With Liver Cancer That Is Metastatic or Cannot Be Removed by Surgery

Study Objectives CERTIM is a cohort created in July 2015 to set up a multidisciplinary follow-up of cancer patients treated with immune checkpoint inhibitors. From the CERTIM cohort, we conducted a longitudinal, prospective, observational study (ELY) in two tertiary university centers (Cochin hospital and European Georges Pompidou Hospital), which included patients between August 2016 and October 2019 and ended follow-up in April 2020. Patients were treated with nivolumab, at a dose of 3 mg/kg every 2 weeks, or pembrolizumab, at a dose of 2mg/kg every 3 weeks. The investigators report findings from an evaluation of rest energy expenditure (REE) assessed using indirect calorimetry in the outpatient setting before treatment with checkpoints inhibitors. Conditions: Non-small Cell Lung Cancer, Progression, Disease Intervention / Treatment: OTHER: Resting Energy Expenditure measurement Location: France Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * >= 18 years * Stage IV histologically proven Non Small Cell Lung Cancer (NSCLC) * Monotherapy with nivolumab or pembrolizumab. * Patients were required to have measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Exclusion Criteria: * Active malignancy other than NSCLC, * ALK or EGFR mutated NSCLC * Anticancer therapy or surgery within the past 2 weeks or inability to breathe under the calorimetry.

NCT_ID NCT04879316

Study_NameEnergy for Lymphocytes

Study Objectives This study is proposed based on our work showing that the diabetes drug Pioglitazone strongly inhibits growth of tissue cultured squamous cell carcinoma (SCC) of the skin. This occurs at concentrations readily achievable by oral administration of this drug using doses currently approved for the treatment of diabetes. In our study, we propose to enroll 40 non-diabetic adult subjects (18-80 yrs of age inclusive) with a documented clinical history of frequent occurrence of skin squamous cell cancer to receive Pioglitazone (Actos®,Takeda Pharmaceuticals). Each subject will receive usual care for all new tumors they develop while on study (i.e, excision and plastic repair). The study protocol will randomize (1:1) patients for 6 months of observation followed by 6 months of treatment (group 1) or 6 months of treatment with drug followed by observation for 6 months (to examine washout effects). The biopsy specimens collected on and off therapy will be examined to determine if they express AKR1C3, an enzyme we believe increases resistance of SCC to prostaglandin inflammatory mediators. We will also examine the histologic grade of the removed tumors and study whether Pioglitazone treatment can decrease the number of aggressive versus well differentiated tumors in study patients. This pilot study is designed to detect a statistically significant change in SCC tumor numbers but is not sponsored by the drug manufacturer. The data obtained will not be used to effect a change in the product label. Conditions: Squamous Cell Carcinoma of the Skin Intervention / Treatment: DRUG: Pioglitazone Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * >18 years, male or female, state of health stable * Able understand protocol and give consent * Has had treatment of 2 - 6 squamous cell carcinomas of the skin during the year prior to enrollment, & pathology is available for verification * Stable treatment regimen for their skin cancer problems in place for 1 year, with expectation to keep medications the same during study * Able to keep study appointments & comply with protocol Exclusion Criteria: * Unwillingness or unable to complete informed consent process * < 18 years * Allergy to Pioglitazone * Taking Rifampin, Trimethoprim, Celebrex or Gemfibrozil * Pregnant or breastfeeding (Pregnancy Category C) * History of heart failure NYHA Class III or Class IV * Subjects with type 1 or type 2 diabetes * Problems with pedal edema * Liver disease (ETOH, viral hepatitis, drug-induced hepatitis) or elevated ALT, AST or total bilirubin * Osteoporosis with high risk of fracture * History of bladder cancer * Recent change in chronic oral medications. Participants enrolled while on a systemic medication for their skin cancer must remain on treatment.

NCT_ID NCT02347813

Study_NamePreventing Squamous Cell Skin Cancer

Study Objectives For advanced head and neck cancer, combined radiation and chemotherapy prevents recurrences and for many patients, improves survival. While combined cisplatin and radiation or cetuximab and radiation is more effective than radiation alone, approximately 50% of these patients will still recur. A more aggressive approach may be needed for these patients to prevent recurrence and death. The strategy of using multiple chemotherapy drugs with radiation given twice a day has been tested at Mount Sinai and University of Chicago. Approximately 80% of patients are cured with this strategy. While cure rates are higher than standard chemotherapy and radiation and the treatment is tolerable, side effects during treatment are common. We propose replacing a chemotherapy drug with a less toxic, targeted therapy called cetuximab. Our goal is to reduce toxicity while maintaining or improving cure rates for these patients. Conditions: Head and Neck Cancer, Cancer of the Pharynx, Cancer of the Larynx, Nose Neoplasms, Paranasal Sinus Neoplasms, Cancer of the Oral Cavity Intervention / Treatment: DRUG: Cetuximab, DRUG: Hydroxyurea, DRUG: Fluorouracil, PROCEDURE: radiotherapy Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Age >= 18 years * Histologically or cytologically confirmed diagnosis of squamous cell or poorly differentiated carcinomas of the head and neck or lymphoepithelioma * No prior chemotherapy or radiotherapy * Prior surgical therapy will consist only of incisional or excisional biopsy, and organ sparing procedures such as debulking of airway-compromising tumors or neck dissection in a patient with an existing primary tumor * Karnofsky performance status of >= 70% * Intact organ and bone marrow function * Obtained informed consent Exclusion Criteria: * Demonstration of metastatic disease (i.e. M1 disease). * Patients with a history of severe allergic reaction to docetaxel or other drugs formulated with polysorbate 80. History of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, 5-fluorouracil, or hydroxyurea. * Other coexisting malignancies or malignancies diagnosed within the previous 3 years with the exception of basal cell carcinoma, cervical cancer in situ, and other treated malignancies with no evidence of disease for at least 3 years. * Prior surgical therapy other than incisional or excisional biopsy and organ-sparing procedures such as debulking of airway-compromising tumors or neck dissection in a patient with an unknown primary tumor. Any non-biopsy procedure must have taken place less than 3 months from initiating protocol treatment. * Incomplete healing from previous surgery * Pregnancy or breast feeding (men and women of child-bearing potential are eligible but must consent to using effective contraception during therapy and for at least 3 months after completing therapy) * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Patients with clinically significant pulmonary dysfunction, cardiomyopathy, or any history of clinically significant CHF are excluded. The exclusion of patients with active coronary artery disease will be at the discretion of the attending physician. * Uncontrolled active infection unless curable with treatment of their cancer.

NCT_ID NCT00462735

Study_NameFluorouracil, Hydroxyurea, Cetuximab and Twice-daily Intensity Radiation Therapy for Advanced Head and Neck Cancer

Study Objectives The purpose of this study is to find out whether the combination of avelumab and SBRT is safe and what effect avelumab has on mesothelioma when given in combination with SBRT. In addition, a goal of this protocol is to study the effect of radiation therapy on the immune system. It is thought that radiation treatment may create a form of 'vaccine' against cancer inside the body and immunotherapy may improve this effect. The combination of radiation treatment and immunotherapy may be more effective against cancer than either radiation or immunotherapy alone. Conditions: Malignant Mesothelioma (MPM) Intervention / Treatment: DRUG: Avelumab, RADIATION: Stereotactic Body Radiation Therapy Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patient willing and able to provide written informed consent for the trial. * Patient age >= 18 at time of consent. * Histologically or cytologically confirmed malignant pleural or peritoneal mesothelioma (MPM). * No plans for surgical resection. * At least one prior line of systemic therapy. Note: Patients on prior immunotherapy are eligible. * At least one targetable lesion appropriate for palliative SBRT and one non-target lesion * Karnofsky Performance Score (KPS) >= 70% * If of childbearing potential, must be willing to use highly effective mode of contraception for at least one month prior, during, and for 2 months after the end of active therapy * Adequate organ function, defined as: * Absolute Neutrophil Count >= 1.5K/mcL. * Platelet count >= 100K/mcL. * Adequate renal function as defined by an estimated creatinine clearance >= 30 mL/min according to the Cockcroft-Gault formula or serum creatinine <= 1.5 x ULN * Hemoglobin > 9g/dL (prior transfusion permitted) * Total bilirubin level <= 1.5 × the upper limit of normal (ULN) range * AST and ALT levels <= 2.5 × ULN or AST and ALT levels <= 5 x ULN (for subjects with documented metastatic disease to the liver). * If the patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. Exclusion Criteria: * Currently participating and receiving another study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. * Prior radiation therapy precluding SBRT * Continuous oxygen use * Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses <= 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). * Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. * Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade >= 3) * Patient who rapidly progressed on prior immunotherapy, as determined by the treating physician, are not eligible. * Prior Therapies: 1. Treatment with a monoclonal antibody within 4 weeks prior to study Day 1 or has not recovered (i.e., >= Grade 1 at baseline) from adverse events due to agents administered 2. Prior chemotherapy, targeted small molecule therapy, within 4 weeks prior to study Day 1 or has not recovered (i.e., >= Grade 1 at baseline) from adverse events due to a previously administered agent (excluding Grade 2 neuropathy). 3. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti- Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) within 4 weeks prior to study Day 1 or has not recovered (i.e., >= Grade 1 at baseline) from adverse events * Comorbidities or Prior Conditions: 1. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 2. Prior organ transplantation including allogenic stem-cell transplantation. 3. Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. 4. Known history of active TB (Tuberculosis). 5. Known history of HIV or known acquired immunodeficiency syndrome. 6. Active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection at screening or positive serologies indicating prior infection. 7. Active infection requiring systemic therapy. 8. Evidence of interstitial lung disease or active, non-infectious pneumonitis. 9. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (>= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication. * Pregnant women or women who are breastfeeding or of childbearing potential and not using a highly effective method of birth control for at least one month prior to enrollment. If the risk of contraception exists, male and female subjects must use highly effective contraception throughout the study and for at least 60 days after last avelumab treatment. a. Highly effective contraception includes either 2 barrier methods (diaphragm, condom by the partner, copper intrauterine device, sponge, or spermicide), or 1 barrier method and 1 hormonal method (any oral, subcutaneous, intrauterine, or intramuscular registered and marketed contraceptive agent that contains an estrogen and/or a progesterone agent). * Vaccination within 4 weeks prior to the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines. * Concomitant use of the following medications 1. Any investigational anticancer therapy. 2. Any concurrent chemotherapy, immunotherapy, or biologic therapy. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable. 3. Immunosuppressive medications including, but not limited to systemic corticosteroids (>10 mg/day prednisone or equivalent), methotrexate, azathioprine, and tumor necrosis factor alpha (TNF-α) blockers. Use of immunosuppressive medications for the management of investigational product-related AEs, in subjects with contrast allergies is acceptable. In addition, use of inhaled and intranasal corticosteroids is permitted. * Known contraindications to radiotherapy

NCT_ID NCT03399552

Study_NameStereotactic Body Radiation Therapy and Avelumab Immunotherapy for Treatment of Malignant Mesothelioma

Study Objectives The best dose of radiation to be given with bevacizumab is currently unknown. This study will use higher doses of radiation with bevacizumab than have been used before. This study will test the safety of radiation given at different doses with bevacizumab to find out what effects, good and/or bad, it has on the patient and the malignant glioma or related brain cancers. Conditions: Brain Cancer, MALIGNANT GLIOMA, Glioblastoma, Anaplastic Astrocytoma (AA), Anaplastic Oligodendroglioma (AO), Anaplastic Oligo-astrocytoma (AOA), Anaplastic Mixed Gliomas, Malignant Glioma NOS Intervention / Treatment: OTHER: Bevacizumab & Stereotactic Radiotherapy Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must have EITHER * Histologically confirmed intracranial malignant glioma of the following types: Glioblastoma, Anaplastic astrocytoma (AA), Anaplastic oligodendroglioma (AO), Anaplastic oligo-astrocytoma (AOA) also called anaplastic mixed gliomas, Malignant glioma NOS (not otherwise specified). Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a high grade (malignant) glioma is made. OR * Histologically confirmed low grade (WHO grade II) gliomas (such as low grade astrocytoma, low grade oligodendroglioma, low grade oligo-astrocytoma (mixed gliomas), or low grade glioma NOS) IF there is radiographic evidence by MRI of malignant transformation but histologic confirmation of high grade (malignant) transformation would not be otherwise undertaken for routine clinical care. Inclusion of patients in this group will allow increased accrual rapidity by enrolling patients who are otherwise ineligible for almost all malignant glioma trials yet whom are treated presumptively for malignant glioma. The primary aim of the phase I study is not determination of efficacy. Therefore, inclusion of such patients will not affect efficacy analyses. Participating site confirmation is adequate. * Able to undergo brain MRI scans. * MRI scan with gadolinium contrast showing geographically-circumscribed tumor <=40 cc incorporating both enhancing and non-enhancing volume. This is calculated by the product of maximum measurements in 3 dimensions divided by 2. Tumors exceeding this limit may be eligible and any question should be directed to a Radiation Oncology Investigator and the MSK PI. (The MRI must be performed on a steroid dosage that has been stable or decreasing for at least 5 days. Patients on no steroids are eligible. If the steroid dose is increased between date of imaging and registration, a new baseline MRI is required). * Prior treatment with approximately 60 Gy of radiotherapy. * Patients must have recovered from the toxic effects of prior therapy including but not limited to: * An interval of >= 4 weeks (28 days) from prior cytotoxic therapy except 6 weeks from nitrosoureas * An interval of >= 1 week (7 days) from any non-cytotoxic agents * An interval of >= 3 months from the completion of radiation therapy * Absolute neutrophil count >= 1,500/mm3. * Platelet count >= 100,000/mm3. * Hemoglobin >= 10 g/dl. * Serum creatinine <= 2 times upper limit of normal. * Total bilirubin <= 2 times upper limit of normal. * SGOT and SGPT both <= 3 times upper limit of normal. * >=18 years. * Karnofsky Performance Score >= 60 * Life expectancy >= 12 weeks * Men and women with reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment. * Written informed consent prior to registration on study. Exclusion Criteria: * Prior treatment with radiosurgery * Prior disease progression/recurrence during or immediately following treatment with bevacizumab. Any question should be directed to the PI. * Multicentric glioma * Other malignancy (with the exception of cervical carcinoma in situ or basal cell carcinoma of the skin) for which there has been treatment within the last 3 years * Serious medical or psychiatric illness that would in the opinion of the investigator interferes with the prescribed treatment. * Pregnant or breast feeding women * Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg) * Any prior history of hypertensive crisis or hypertensive encephalopathy * Grade 2 or greater congestive heart failure * History of myocardial infarction, unstable angina, stroke, or transient ischemic attack within 12 months prior to Day 1 * Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1 * History of hemoptysis >=1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1 * Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of treatment or anticipation of need for major surgical procedure during the course of the study * Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1 * Serious, non-healing wound, active ulcer, or untreated bone fracture * Proteinuria as demonstrated by a UPC ratio >= 1.0 at screening * Known hypersensitivity to any component of bevacizumab * History of peptic ulcer within the last 6 months * Clinically significant peripheral vascular disease * Craniotomy wound that has not sufficiently healed * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment * Glioma showing prior spontaneous hemorrhage as determined from the clinical history or from any preoperative CT or MRI scan (excluding grade 1 punctate, incidentally found). * Longest uni-dimensional measurement of contrast enhancing tumor >= 4cm. Tumors exceeding this limit may be eligible and any question should be directed to a Radiation Oncology Investigator and the MSK PI. * Tumor must not invade the corpus callosum * Tumor must not invade the brainstem * Suspected or documented radionecrosis

NCT_ID NCT01392209

Study_NameHypofractionated Stereotactic Radiotherapy With Bevacizumab in the Treatment of Recurrent Malignant Glioma

Study Objectives The purpose of this study is to test the safety and tolerability of ruxolitinib at different dose levels in combination with decitabine and the effectiveness of ruxolitinib in combination with decitabine in patients with accelerated or blast phase Myeloproliferative Neoplasm (MPN), which is a group of diseases of the bone marrow in which excess cells are produced. Ruxolitinib is a drug that is approved by the Federal Drug Administration (FDA) for the treatment of patients with advanced forms of myelofibrosis. It inhibits the Jak proteins that are often abnormal in MPN. A recent clinical study showed that ruxolitinib treatment could put some patients with this disease into remission. Decitabine is a chemotherapy, approved by the Federal Drug Administration (FDA), that has been used to treat acute leukemia. It works in some patients, but most patients with accelerated and blastic MPN do not respond to treatment. Ruxolitinib and decitabine will be combined in this study to find out what dose of the two medicines are safe together. Using Ruxolitinib in combination with Decitabine is experimental. The investigators want to find out what effects, good and/or bad it has on the patient and the disease. Conditions: Myeloproliferative Neoplasms Intervention / Treatment: DRUG: Ruxolitinib, DRUG: Decitabine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Accelerated phase MPN as defined by 10%-19% blasts in the peripheral blood or bone marrow and evidence of dysplastic marrow features with a concomitant diagnosis of essential thrombocythemia (ET), polycythemia vera (PV) or primary myelofibrosis (PMF) or a diagnosis of acute myelogenous leukemia as defined by 20% blasts in the blood or bone marrow following a previous diagnosis of ET, PV or PMF. * >18 years * Eastern Cooperative Oncology Group (ECOG) Performance status of 0 <= age <= 2. Patients with ECOG performance status of 3 will be eligible if the lower performance status is deemed by the investigator to be due entirely to accelerated or blastic phase MPN and not due to another comorbidity. * Acceptable pre-study organ function during screening as defined as: Total bilirubin < 1.5 times the upper limit of normal (ULN) unless due to Gilbert's disease or hemolysis, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 times ULN, Serum creatinine <= 1.5 x ULN * Women of childbearing potential and males must agree to use adequate contraception (i.e., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a female subject become pregnant or suspect she is pregnant while participating in this study, she should inform the treating physician immediately. * Patients who are not candidates for or have declined an allograft. * Ability to understand and willingness to sign a written informed consent document. Exclusion Criteria: * Have had chemotherapy or investigational therapy, with the exception of hydroxyurea, within 4 weeks of study entry. Previous treatment with either ruxolitinib or decitabine as single agents will not exclude eligibility. Previous stem cell transplant will also not exclude eligibility as long as other inclusion/exclusion criteria have been met. * Patients with acute myelofibrosis are excluded. * Uncontrolled intercurrent illness including, but not limited to hepatitis, human immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Other medications, severe acute/chronic medical or psychiatric conditions, or laboratory abnormalities that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, that in the judgment of the Investigator would make the subject inappropriate for entry into this study.

NCT_ID NCT02076191

Study_NameStudy of Combination Ruxolitinib and Decitabine Treatment for Accelerated Phase MPN or Post-MPN AML

Study Objectives This 2 arm study will compare the efficacy and safety of Taxotere + Xeloda, versus Taxotere alone, following a regimen of Adriamycin plus Cytoxan in women with high-risk breast cancer. Following 4 cycles of Adriamycin and Cytoxan, patients will be randomized to receive either 1)Taxotere 75mg/m2 iv on day 1 and Xeloda 825mg/m2 po bid on days 1-14 of each 3 week cycle or 2) Taxotere 100mg/m2 iv alone on day 1 of each 3 week cycle. The anticipated time on study treatment is until disease progression, and the target sample size is 500+ individuals. Conditions: Breast Cancer Intervention / Treatment: DRUG: capecitabine [Xeloda], DRUG: Taxotere, DRUG: Taxotere Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * female patients 18 <= age <= 70 years; * adenocarcinoma of the breast; * previous invasive breast cancer if diagnosed >5 years before entering study; * no evidence of metastatic disease. Exclusion Criteria: * history of severe hypersensitivity reaction to Taxotere; * previous treatment with anthracycline, anthracenedione (mitoxantrone), or taxane; * treatment with fluoropyrimidine (5-fluorouracil) within the last 5 years.

NCT_ID NCT00089479

Study_NameA Study of Xeloda (Capecitabine) in Women With High-Risk Breast Cancer

Study Objectives The primary objective of the present study is to investigate the influence of co-administration of itraconazole and volasertib on the pharmacokinetic profile of volasertib without co-administration of itraconazole. Secondary objectives are to investigate safety, tolerability and preliminary therapeutic effects following intravenous administration of volasertib. Conditions: Neoplasms Intervention / Treatment: DRUG: volasertib, DRUG: itraconazole Location: Hungary Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion criteria: * Patients with histologically or cytologically confirmed diagnosis of advanced, non resectable and / or metastatic solid tumour, for whom conventional treatment has failed, or for whom no therapy of proven efficacy exists, or who are not amenable to established forms of treatment based on the investigator's assessment * Male or female * Age =>18 and =<70 years * Eastern Cooperative Oncology Group (ECOG) performance score =< 2 * Recovery from Common Terminology Criteria for Adverse Events (CTCAE) Grade >= 2 therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapy (except alopecia) Exclusion criteria: * Serious concomitant non-oncological disease considered by the investigator to be incompatible with the protocol * Active infectious disease * Viral hepatitis, HIV infection * Clinical evidence of active brain metastasis or leptomeningeal disease during the past 6 months * Second malignancy currently requiring active therapy (except for hormonal / antihormonal treatment e.g. in prostate or breast cancer) * Absolute neutrophil count less than 1,500/mm3 * Platelet count less than 100,000/mm3 * Total bilirubin greater than 1.5 mg/dL (> 26 µmol/L, SI unit equivalent) * Aspartate amino transferase (AST) and / or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal) * Serum creatinine greater than 2x upper limit of normal (ULN) * QTcF prolongation > 470 ms or QT prolongation deemed clinically relevant by the investigator (e.g., congenital long QT syndrome).The QTcF will be calculated as the mean of the 3 ECGs taken at screening * Female patients with childbearing potential and unwilling to use a medically acceptable method of contraception during the trial and for at least six months after end of active therapy. Woman of childbearing potential (premenopausal female) is defined as the female who is not surgically sterilised by hysterectomy or bilateral tubal ligation or post-menopausal for at least 12 months. * Treatment with other investigational drugs or participation in another clinical trial within the past four weeks prior to start of therapy or concomitantly with this trial * Chemo-, radio- immuno-, or molecular-targeted cancer-therapy within the past four weeks prior to start of therapy or concomitantly with this trial. This restriction does not apply to steroids, bisphosphonates hormonal / antihormonal treatment (e.g. in prostate or breast cancer). * Alcohol abuse more than an average 3 units of alcoholic beverages per day or more than 21 units per week (1 unit equals 0.5 pint [285 mL] of beer or lager, 1 glass [125 mL] of wine, 25 mL shot of 40% spirit) or drug abuse * Life expectancy less than 12 weeks * Potent CYP 3A4 and P-glycoprotein inhibitors other than the study drug or inducers between one week prior to first drug administration or expected treatment with a respective drug until the last PK sample is collected 1. Strong CYP 3A4 inhibitors: atazanavir, clarithromycin, indinavir, itraconazole (other then study drug), ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin 2. CYP 3A4 inducers: carbamazepine, rifampicin 3. P-gp inhibitors: cyclosporine, erythromycin, itraconazole (other then study drug), ketoconazole, quinidine, phenobarbital salt with quinidine, ritonavir, valspodar, verapamil 4. P-gp inducers: hypericum perforatum, rifampicin

NCT_ID NCT01772563

Study_NameInvestigation of Potential Drug-drug Interaction of Volasertib With Itraconazole in Patients With Various Tumours

Study Objectives This research study is studying a drug called FCN-437c as a possible treatment for patients with advanced unresectable/metastatic solid tumors. Conditions: Solid Tumor, Adult Intervention / Treatment: DRUG: FCN-437 Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Have given written informed consent prior to any study specific procedures * Male or female subject >= 18 years * Histologically/cytologically confirmed, unresectable locally advanced or metastatic solid tumors that are refractory to standard therapy or for which no standard therapy exists. Note for patients with non-small cell lung cancer [NSCLC] and patients with activating ALK translocation, or EFGR mutations must have been treated and failed appropriate targeted treatment). Subjects enrolled in cohort expansion at MTD should have specific tumor types as below: * KRAS mutant NSCLC confirmed by a documented historical report * Breast cancer previously treated with a CDK4/6 inhibitor * All subjects should have evaluable disease as per RECIST 1.1 (Eisenhauer, 2009). Subjects enrolled in cohort expansion at MTD should have measurable disease (presence of at least one measurable lesion) as per RECIST 1.1. * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) <= 1 * Subjects with life expectancy of >= 3 months * Subjects with central nervous system (CNS) metatases are eligible if clinically controlled that is defined as surgical excision/and or radiation therapy followed by 3 weeks of stable neurologic function and no evidence of CNS disease progression as determined by contrast-enhanced computer tomography (CT) and nuclear magnetic resonance imaging (MRI) within 3 weeks prior to the first dose of study drug. * Must have adequate organ function, including the following: * Bone marrow reserve: absolute neutrophil count (ANC) >= 1.5 X 10 9/L; platelet count >= 100 x 10 9/L;hemoglobin >= 9g/dL or >= 5.6 mmol/L * Hepatic: total bilirubin <= 1.5 times the upper limit of normal (ULN), aspartate transaminase (AST) and/or alanine aminotransferase (ALT) <= 2.5 times ULN (< 5 times ULN if liver metastases). * Renal: estimated creatinine clearance >= 45 mL/min based on the Cockcroft-Gault equation (Appendix 19.4). * Coagulation: INR < 2.0, activated partial thromboplastin time (aPTT) <= 1.5 x ULN. * Subjects are able to swallow capsules. * Subjects (women of child-bearing potential and males) should be willing to use viable contraception method that is deemed effective by the Investigator throughout the treatment period and for at least 3 months following the last dose of study drug. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Exclusion Criteria: * Females during pregnancy or breastfeeding. * Subjects on any anticancer therapy approved or experimental, including chemotherapy, immune therapy, radiation therapy, hormonal therapy (Exceptions: hormone-replacement therapy, testosterone or oral contraceptives), biologic therapy, within 3 weeks (or 5 half-lives whichever is shorter) prior to initiation of study treatment. Note: Subjects should be recovered from treatment related toxicity resolved to baseline except for residual alopecia. * Subjects who had prior treatment with a CDK4/6 inhibitor except Hormone receptor (HR)+/Human epidermal growth factor receptor 2 (HER2)- breast cancer patients who may have received CDK4/6 inhibitor as a standard treatment. * Subjects with history of gastric bypass surgery or banding procedure. * Subjects who have had major surgery within the 28-days from the screening or subjects who have undergone organ transplant surgery. * Active hepatitis B (HBV) or hepatitis C (HCV). HBV carriers without active disease (HBV DNA titer < 1000 cps/mL or 200 IU/mL), or cured HCV (negative HCV RNA test) may be enrolled. Subjects with controlled human immunodeficiency virus (HIV) disease may be eligible. * Subjects with a concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator or Sponsor. * Unresolved toxicities (other than alopecia) from previous anti-cancer therapy defined as toxicities not resolved to NCI CTCAE Version 5.0, Grade <= 1. * Subject who have had severe infection within 4 weeks or signs and symptoms of any active infection within 2 weeks prior to the first dose administration. * Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure New York Heart Association (NYHA) III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 3 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia). * A resting ECG with QTcF >= 470 msc or the subject has a congenital prolonged QT syndrome or with concomitant medications known to prolong the QT interval. * Taking a prohibited concomitant medication or inability to follow concomitant medications guidelines * Any other serious underlying medical (e.g., uncontrolled diabetes mellitus, uncontrolled hypertension, active uncontrolled infection, active gastric ulcer, uncontrolled seizures, severe hearing impairment, cerebrovascular incidents, gastrointestinal bleeding, severe signs and symptoms of coagulation and clotting disorders, cardiac conditions), psychiatric, psychological, familial or geographical condition that, in the judgment of the Investigator, may interfere with the planned staging, treatment and follow-up, affect subject compliance or place the subject at high risk from treatment-related complications.

NCT_ID NCT03951116

Study_NameStudy of FCN-437c in Patients With Advanced Solid Tumors

Study Objectives This study will investigate clinical activity, safety, and tolerability of the anti-angiogenic compound cilengitide (EMD 121974) in the treatment of first recurrence of glioblastoma multiforme (GBM). Conditions: Glioblastoma Multiforme Intervention / Treatment: DRUG: Cilengitide 500 mg, DRUG: Cilengitide 2000 mg Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Written informed consent obtained before undergoing any study-related activities. * Males or females 18 years or older who can be treated in an outpatient setting. * Histologically proven GBM, which is recurrent or progressive following surgery or biopsy, external beam radiation therapy, and 1 previous regimen of systemic chemotherapy (Gliadel wafer therapy is not considered systemic chemotherapy). Malignancy is to be documented with a previous histopathological report. * Subjects initially diagnosed with other conditions similar to GBM (such as anaplastic astrocytoma [AA] or low grade glioma) that subsequently progressed to histologically proven GBM and have had surgery or biopsy, external beam radiation therapy, and 1 previous regimen of systemic chemotherapy for the original diagnosis are eligible if they meet all inclusion criteria. * GBM recurring only in the contralateral hemisphere must be histologically confirmed by biopsy. GBM recurring bilaterally does not need to be histologically confirmed by biopsy (i.e., if recurrence is ipsilateral and contralateral). * Archived tumor tissue specimens from the GBM surgery or biopsy must be available for central pathology review and exploratory analysis of angiogenic markers (e.g. αvβ3 and αvβ5 integrins). * Measurable disease (solid contrast-enhancing lesion greater than or equal to (>=)1 cm in any dimension) evaluated by gadolinium-enhanced magnetic resonance imaging (Gd MRI) within 2 weeks prior to the first dose of EMD 121974. * At least 12 weeks have elapsed since the last radiation treatment, and at least 4 weeks have elapsed since the last chemotherapy dose (at least 6 weeks for nitrosourea-containing chemotherapy) prior to the first dose of EMD 121974. * If the subject underwent recent surgery, status must be >=2 weeks post surgery or >=1 week post biopsy, in stable condition, and maintained on a stable corticosteroid regimen for >=5 days prior to first dose of EMD 121974. * Karnofsky Performance Score (KPS) of >=70%. * Subjects with the potential for pregnancy or impregnating their partner must agree to follow acceptable methods of birth control to avoid conception during the study and for at least 6 months after receiving the last dose of study drug. * Women of childbearing potential must have a negative pregnancy test at screening. * Laboratory values (within 1 week prior to the first dose of EMD 121974, except for blood count and Prothrombin time (PT)/Partial thromboplastin time (PTT), which are to be within 72 hours of the first dose): Absolute neutrophil count >=1500/millimeter (mm)^3. Platelets >=100,000/mm^3. Creatinine less than or equal to (<=) 1.5 milligram/deciliter (mg/dL) or creatinine clearance >=60 mL/min. Hematocrit >=30%. Prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits. Hemoglobin >=10 mg/dL. Total bilirubin <=1.5 times the upper limit of normal. Aspartate aminotransferase and alanine aminotransferase <=2.5 times above upper limit of normal. * No more than 8 weeks have elapsed since recurrence was detected Exclusion Criteria: * Prior radiation therapy greater than (>) 66 Gray. * Subject anticipates undergoing elective surgery, dental extraction, or invasive dental procedures. * History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months of enrollment. * History of prior malignancy. Subjects with curatively treated cervical carcinoma in situ or basal cell carcinoma of the skin, or subjects who have been free of other malignancies for >=5 years are eligible for this study. * History of coagulation disorder associated with bleeding or recurrent thrombotic events. * Concurrent illness, including severe infection, which may jeopardize the ability of the subject to receive the procedures outlined in this protocol with reasonable safety. * Subject is pregnant, anticipates becoming pregnant within 6 months after study participation, or is currently breast-feeding. * Receiving concurrent investigational agents or has received an investigational agent within the past 30 days prior to the first dose of EMD 121974. * Prior antiangiogenic therapy. * Placement of Gliadel wafer at surgery for recurrence. * Unable to undergo Gd MRI. * Current known alcohol dependence or drug abuse. * Requiring concomitant chemotherapy. * Treatment with a prohibited concomitant medication. * Known hypersensitivity to the study treatment. * Legal incapacity or limited legal capacity.

NCT_ID NCT00093964

Study_NameCilengitide (EMD 121974) for Recurrent Glioblastoma Multiforme (Brain Tumor)

Study Objectives The aim of this study is to demonstrate the bioequivalence of DOXIL/CAELYX, 40 mg/m2 (IV infusion over 90 minutes) between two manufacturing facilities. According to the Food and Drug Administration (FDA), two products are considered to be bioequivalent when they are equal in the rate and extent to which the active pharmaceutical ingredient (API) becomes available at the site(s) of drug action. Any abnormalities of the safety endpoints (Clinical Laboratory Test, Electrocardiogram, Left Ventricular Ejection Fraction, Physical Examination) will be captured as Adverse Events. Conditions: Ovarian Cancer, AIDS-related Kaposi Sarcoma, Multiple Myeloma, Metastatic Breast Cancer Intervention / Treatment: DRUG: DOXIL/CAELYX Location: India Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * Be a man or woman aged from 18 <= age <= 75, inclusive. * Patients with advanced or refractory ovarian or breast cancer, expected to require at least 2 cycles of DOXIL/CAELYX therapy at Screening, are eligible for treatment per this study protocol. This includes: 1. Histologically or cytologically confirmed advanced ovarian cancer failing platinum-based chemotherapy 2. Histologically or cytologically confirmed metastatic breast cancer after failing approved life-prolonging therapies * Life expectancy greater than 6 months based on the clinical evaluation by the investigator at the time of Screening. * Eastern Cooperative Oncology Group (ECOG) Performance status 0 to 2, inclusive. * Recovered from the acute toxicity of any prior treatment (exemptions: alopecia, neuropathy Grade I). All toxicities from prior treatment should return to baseline or Grade I. * Prior doxorubicin (or other anthracyclines) at cumulative dose of <= 240 mg/m2 or cumulative epirubicin dose <= 720 mg/m2 (calculated using doxorubicin equivalent doses: 1 mg doxorubicin = 1 mg DOXIL/CAELYX = 0.3 mg mitoxantrone = 0.25 mg idarubicin). Patients without any prior anthracycline exposure can also be included. * Adequate liver function as determined by serum total bilirubin levels <= 1.2 mg/dL, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels <= 2.5 x ULN. * Adequate bone marrow function, as determined by an absolute neutrophil count (ANC) >= 1500/mm3 (or >= 1.5 x 109/L), a platelet count >= 100,000/mm3 (or >= 100 x 109/L), and a hemoglobin level >= 9 g/dL (or >= 90 g/L), in the absence of transfusion requirements or cytokine support for at least 7 days prior to enrolling in the study. * Adequate renal function (mL/min), as determined by multiplying estimated glomerular filtration rate (e-GFR) by the body surface area (BSA) and dividing the value by 1.73 m2. * Left ventricular ejection fraction (LVEF) within normal limits of the institution, as determined by multiple uptake gated acquisition (MUGA) or echocardiography. * Female patients (of childbearing potential) must use medically acceptable methods of birth control (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patches, intrauterine devices, the double-barrier method, male partner sterilization) before enrollment, throughout the study and for at least 8 months after the last DOXIL/CAELYX infusion. * Male patients must agree to use an adequate contraception method as deemed appropriate by the Investigator and always use condoms when sexually active during the study. Medically acceptable methods of contraception that may be used by the patient and/or his partner include oral contraceptives, contraceptive injections, contraceptive patches, intrauterine devices, the double-barrier method, and surgical sterilization (vasectomy or tubal ligation) for minimally 6 months after the last administration of DOXIL/CAELYX. Sperm donation is not allowed during the study and for minimally 6 months after the last administration of DOXIL/CAELYX. * Negative pregnancy test (urinary or serum beta-human chorionic gonadotropin [β-HCG]) at Screening (applicable to women of childbearing potential) within 7 days prior to starting treatment. * Patients with no history of addiction to any recreational drug or drug dependence or alcohol addiction. * Patients must have signed an informed consent form indicating that they understand the purpose and procedures required, and are willing to participate in the study. Exclusion Criteria: * Positive history of known brain metastases or leptomeningeal disease. Patients with brain metastases can only be enrolled if the following conditions are all met: 1. Brain metastases have been treated and stable for > 4 weeks (> 2 weeks after SRS/Cyberknife) 2. No evidence for progression or hemorrhage after treatment 3. Steroid treatment was discontinued at least 2 weeks prior to first administration of DOXIL/CAELYX 4. Enzyme inducing anti-epileptic drugs were discontinued at least 4 weeks before the first administration of DOXIL/CAELYX * Has a history of hypersensitivity reaction to doxorubicin HCl or other components of DOXIL/CAELYX. * Has a history of prior or concomitant malignancy that requires other active treatment. * Require any antineoplastic treatment while on the study (including therapy with another agent, radiation therapy, and/or surgical resection). * Any major surgery, radiotherapy, or immunotherapy within the last 21 days (limited palliative radiation is allowed >= 2 weeks prior to the first dose; >= 4 weeks for whole brain radiotherapy). Chemotherapy regimens with delayed toxicity within the last 3 weeks (or within the last 6 weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last 2 weeks or 5 half-lives (whichever is shorter). * Use of an investigational drug within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of DOXIL/CAELYX. * Impaired cardiac function including any of the following conditions within the past 6 months: 1. Unstable angina 2. QTc prolongation (QTc > 470 millisecond) or other significant ECG abnormalities 3. Coronary artery bypass graft surgery 4. Symptomatic peripheral vascular disease 5. Myocardial infarction 6. NYHA class II-IV heart failure 7. Severe uncontrolled ventricular arrhythmias 8. Clinically significant pericardial disease 9. Electrocardiographic evidence of acute ischemic or active conduction system abnormalities 10. Patients with evidence of abnormal cardiac conduction (e.g. bundle branch block or heart block) are eligible if their disease has been stable for the past six months 11. Severe uncontrolled arrhythmias * Has an infection that is either uncontrolled, clinically important (occurred within 4 weeks prior to first dose of study agent), or requiring current systemic IV treatment. * Patients with active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, P. carinii or other microorganism if under treatment with myelotoxic drugs * Patient has received a diagnosis of COVID-19 (diagnosis <= 2 months prior and/or symptoms have not resolved). * A patient with uncontrolled concurrent illness including, but not limited to, poorly controlled hypertension or diabetes, or psychiatric illness/social situation that may potentially impair the patient's compliance with study procedures. * Concomitant use of strong CYP3A4 inhibitors (such as clarithromycin, diltiazem, erythromycin, itraconazole, ketoconazole, nefazodone, ritonavir, telithromycin and verapamil) and strong CYP3A4 inducers (such as carbamazepine, phenobarbital, phenytoin, rifampin and St John's wort) from at least 4 weeks before the first dose of DOXIL/CAELYX in Cycle 1 and until after completion of all PK sampling on Day 26 of Cycle 2. * Has any condition that, in the opinion of the Investigator, would make participation not be in the best interest (e.g., compromise the well-being) of the patient or that could prevent, limit, or confound the protocol-specified assessments. * Is a woman who is pregnant, or breast-feeding, or planning to become pregnant within 8 months or is a man who plans to father a child while enrolled in this study or within 6 months after the last dose of study drug. * Is an employee of the Investigator or study site, with direct involvement in the proposed study or other studies under the direction of that Investigator or study site, as well as family members of the employees or the Investigator.

NCT_ID NCT05567601

Study_NameDoxil/Caelyx BE Study

Study Objectives This is a multicenter, double-blind, randomized study comparing the efficacy, pharmacokinetics (PK)/pharmacodynamics (PD), safety and immunogenicity profile of RTXM83 (rituximab biosimilar) vs reference rituximab (MabThera®), both with CHOP, as first-line treatment of Diffuse-Large-B-Cell-Lymphoma (DLBCL). Rituximab biosimilar and MabThera® were both administered intravenously on Day 1 of each 3-week cycle with CHOP chemotherapy for six cycles. Two additional cycles of treatment were permitted at the Investigator's discretion. Patients were followed up for 9 months after last study dose. Conditions: Diffuse Large B-cell Lymphoma Intervention / Treatment: BIOLOGICAL: RTXM83, BIOLOGICAL: Mabthera Location: Malaysia, Indonesia, Philippines, Brazil, South Africa, Argentina, Paraguay, Mexico, Russian Federation, Colombia, Iran, Islamic Republic of, India Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * Patients with measurable disease defined as existence of a unidimensional or bidimensional lesion greater than 2 cm in its longest diameter or malignant lymphocytosis greater than 5x109/L. Any other procedure for measurable disease in particular cases, may be allowed upon Sponsor approval * Newly diagnosed patients with a confirmed pathologic diagnosis of Diffuse large B cell-non-Hodgkin's lymphoma (DLBCL) with untreated CD20+ receptor (CD20+). Defined by the local Haematopathologist at the local laboratory according to World Health Organization (WHO) criteria * Stage II-III or IV or stage I with bulk defined by the referring physician on the basis of the Cotswolds modification of the Ann Arbor classification 2 * Age-adjusted International Prognostic Index (IPI) score 0 or 1 * Age >=18 to <=65 years * Performance status according to Eastern Cooperative Oncology Group (ECOG) of <=2 * Written informed consent obtained before starting any study-specific procedure * Females of child-bearing potential must test negative on standard serum pregnancy test and must be willing to practice appropriate contraceptive methods for the duration of the study (e.g. oral contraceptive, double barrier method, intra-uterine device, intra-muscular contraceptive) * All male patients must take adequate contraceptive precautions during the course of the study Exclusion Criteria: * Life expectancy of less than three months * Any other lymphoma other than CD20+ DLBCL * Indolent lymphoma, Primary central nervous system (CNS) Lymphoma or gastro-intestinal Mucosa Associated Lymphoid Tissue (MALT) Lymphoma * Known hypersensitivity to active ingredients, excipients and murine and foreign proteins * Concurrent disease or general status that would exclude giving the treatment as outlined in the protocol * Active uncontrolled infection requiring systemic treatment with antibiotics or antiviral agents at Screening or history of documented recurrent clinically significant infection (e.g. 2 or more viral, bacterial or fungal infections requiring inpatient treatment) * Cardiac contra-indication to Doxorubicin therapy: non-compensated heart failure, dilated cardiomyopathy, coronary heart disease with ST segment depression on electrocardiogram (ECG), myocardial infarction in the last 6 months * Neurologic contra-indication to Vincristine as it is indicated in the Summary of Product Characteristics (SmPC): (e.g. peripheral neuropathy) * Chronic lung disease with hypoxemia measured by pulse oximetry (gasometry is not mandatory) * Severe uncontrolled hypertension, despite optimal medical treatment * Severe uncontrolled diabetes mellitus, despite optimal medical treatment * Renal insufficiency (Serum Creatinine >2 x Upper Normal Limit [UNL]) * Hepatic insufficiency: aspartate aminotransferase (AST)/ alanine aminotransferase (ALT)>3 x UNL or >5 x UNL with involvement of the liver, total bilirubin >34.2 µmol/L, or both) not related to lymphoma * Clinical signs of cerebral dysfunction * Severe psychiatric disease * Known human immunodeficiency virus (HIV) infection or active chronic hepatitis B or C * Abnormal bone marrow function (platelets <100x109/L, neutrophils <1.5x109/L and Haemoglobin <9g/dL) * Post-transplantation lymphoproliferative disease * Pregnant or lactating women or women that intend to get pregnant during study or within 12 months following the last infusion * Treatment with any investigational product in the 30 days period before inclusion in the study * Prior radiotherapy to treat the DLBCL Non-Hodgkin's Lymphoma (NHL) * Limitation of the patient's ability to comply with the treatment or follow-up protocol

NCT_ID NCT02268045

Study_NameStudy of RTXM83 Plus CHOP Chemotherapy Versus a Rituximab Plus CHOP Therapy in Patients With Non Hodgkin's Lymphoma

Study Objectives This phase II trial studies how well combination chemotherapy works in treating patients with advanced stomach, gastroesophageal, or esophageal cancer. Drugs used in chemotherapy, such as irinotecan hydrochloride, oxaliplatin, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Conditions: Stomach Neoplasms, Esophageal Neoplasms Intervention / Treatment: DRUG: Irinotecan, DRUG: Trastuzumab, DRUG: Oxaliplatin, DRUG: Leucovorin, DRUG: Fluorouracil Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Biopsy-proven and inoperable locally advanced, recurrent, or metastatic cancer of the esophagus, stomach, or gastro-esophageal junction. * Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >=10 mm with CT scan, as >=20 mm by chest x-ray, or >=10 mm with calipers by clinical exam. * Prior single modality radiation therapy is allowed. * At least 18 years. * ECOG performance status <= 2 * Normal bone marrow and organ function as defined below: 1. Absolute neutrophil count >= 1,500/mcl 2. Platelets >= 100,000/mcl 3. AST(SGOT)/ALT(SGPT) <= 2.5 x IULN 4. Creatinine <= IULN OR creatinine clearance >= 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal 5. LVEF >= 50% * Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. * Ability to understand and willingness to sign an IRB approved written informed consent document (legally authorized representative is allowed). * Patients already receiving treatment with FOLFIRINOX +/- trastuzumab may participate in the study and have their data collected retrospectively if they met inclusion criteria at the start of therapy and sign consent for study participation moving forward. Exclusion Criteria: * Chemotherapy in the 6 months prior to registration. * Any active malignancy within 3 years that may alter the course of esophageal cancer (Apparently cured localized malignancy or advanced, but indolent malignancy with significantly more favorable prognosis are allowed) * Receiving any other investigational agents at the time of registration. * Known untreated brain metastases. These patients must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. * A history of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in the study. * Previous therapy for metastatic gastroesophageal cancer. Previous perioperative chemotherapy is allowed as long as the duration without treatment has been greater than 6 months.. * A history of congestive heart failure, transmural myocardial infarction, symptomatic valvular disease, or high-risk arrhythmia. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant and/or breastfeeding. Patient must have a negative urine pregnancy test within 14 days of study entry. * Known HIV-positivity and on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with trastuzumab. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated. Inclusion of Women and Minorities Both men and women and members of all races and ethnic groups are eligible for this trial.

NCT_ID NCT01928290

Study_NameCombination Chemotherapy in Treating Patients With Advanced Stomach, Gastroesophageal, or Esophageal Cancer

Study Objectives This trial will look at 2 different drug combinations that have well known safety profiles and are known to be active against non small cell lung cancer and combine them with bevacizumab, an experimental drug that has shown effectiveness when added to other drug combinations for advanced non-small cell lung cancer. The primary objective in this study is to see how well this combination of drugs keeps the cancer from getting worse in this elderly population of non-small cell lung cancer patients. Conditions: Lung Cancer Intervention / Treatment: DRUG: Pemetrexed, DRUG: Gemcitabine, DRUG: Bevacizumab, DRUG: Carboplatin Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed non-small cell bronchogenic carcinoma, (adenocarcinoma, or large cell carcinoma) * Patients who have newly diagnosed unresectable stage III or stage IV disease are eligible. * Must be at least 70 years * Must have measurable disease by CT scan * Must be able to be up and about and care for themselves * May not have received prior treatment for stage III or IV disease * Must have adequate white and red blood cells and platelets. * Must be able to take Vitamin B12, Folic Acid and dexamethasone as stated in the study * Must be able to understand the nature of this study and give written informed consent * Adequate liver and kidney function Exclusion Criteria: * Past or current history of cancer with the exception of treated non- melanoma skin cancer or carcinoma in-situ of the cervix, or other cancers cured by local therapy alone and have been disease free for five years * Female patients who are pregnant or are lactating are ineligible * History of unstable angina or myocardial infarction within 6 months prior to beginning bevacizumab * Brain metastasis - cancer that has spread to the brain * Major surgical procedure, open biopsy, or significant traumatic injury within 6 weeks of beginning bevacizumab or anticipation of need for major surgical procedure during the course of the study * Full-dose oral or by vein anticoagulation or receiving anti-clotting therapy within 10 days of starting treatment * Serious nonhealing wound, ulcer, or bone fracture * Bleeding or clotting disorders * Uncontrolled high blood pressure or serious heart arrhythmia requiring medication * History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 6 months prior to beginning bevacizumab * Chronic non-steroidal anti-inflammatory use is not allowed on study * History of stroke or TIAs within the last 6 months Please Note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have.

NCT_ID NCT00456261

Study_NameFirst-Line Treatment of A Comparison of 2 Treatments in Elderly Patients With Advanced NSCLC

Study Objectives Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells. AE-941 may help shrink or slow the growth of non-small cell lung cancer cells. It is not yet known if combination chemotherapy plus radiation therapy is more effective with or without AE-941 for non-small cell lung cancer. This randomized phase III trial is studying combination chemotherapy and radiation therapy given with AE-941 to see how well they work compared to combination chemotherapy and radiation therapy alone in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery Conditions: Adenocarcinoma of the Lung, Adenosquamous Cell Lung Cancer, Large Cell Lung Cancer, Squamous Cell Lung Cancer, Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer Intervention / Treatment: DRUG: shark cartilage extract AE-941, OTHER: placebo, DRUG: cisplatin, DRUG: vinorelbine tartrate, DRUG: carboplatin, DRUG: paclitaxel, RADIATION: radiation therapy Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Histologically or cytologically confirmed newly diagnosed, untreated, unresectable stage IIIA or stage IIIB non-small cell lung cancer * Squamous cell carcinoma, adenocarcinoma, or large cell carcinoma of the lung * Mixed tumors allowed if non-small cell elements identified * Contralateral supraclavicular and/or scalene lymph node involvement allowed * No disease extending into the cervical region * At least 1 bidimensionally or unidimensionally measurable lesion * No pleural effusion unless cytologically negative or too small to safely aspirate * Not scheduled for curative cancer surgery * Performance status - ECOG 0 <= age <= 1 * Absolute neutrophil count greater than 1,500/mm^3 * Platelet count greater than 100,000/mm^3 * Hematocrit greater than 30% * SGOT or SGPT less than 1.5 times upper limit of normal * Bilirubin normal * Creatinine less than 1.5 mg/dL * Creatinine clearance greater than 60 mL/min * No other major medical or psychiatric illness that would preclude study participation or consent * No medical condition that interferes with oral medication intake and/or absorption (gastrectomy or major intestinal resection) * No grade 2 or greater peripheral neuropathy unless secondary to mechanical etiology * No hypersensitivity to fish products * No more than 10% weight loss within past 3 months * No other malignancy within past 3 years except inactive carcinoma in situ of the cervix or nonmelanoma skin cancer * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * At least 30 days since prior chemotherapy * See Disease Characteristics * Recovered from prior major surgery * At least 30 days since prior shark cartilage products * No other concurrent investigational anticancer agents * No other concurrent cartilage products * No other concurrent investigational agents * No concurrent amifostine or other radioprotectants * No concurrent enrollment in other clinical trials

NCT_ID NCT00005838

Study_NameCombination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery

Study Objectives To compare 3 doses of EMD 640744 administered by subcutaneous injection in combination with Montanide® ISA 51 VG with regard to immunological efficacy. The primary target variable is the immune response as assessed by ELISPOT before and until week 17 after vaccination with EMD 640744 in Montanide® ISA 51 VG. Conditions: Advanced Solid Tumors Intervention / Treatment: BIOLOGICAL: EMD 640744, BIOLOGICAL: EMD 640744, BIOLOGICAL: EMD 640744, OTHER: Montanide ISA 51 VG, OTHER: Montanide ISA 51 VG, OTHER: Montanide ISA 51 VG Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Male and female subjects >=18 years * Signed written informed consent * Histologically or cytologically documented metastatic or locally advanced survivin-expressing solid tumor for which no established therapy exists * Disease must be measurable by RECIST criteria or evaluable by clinical, radiographic, or laboratory criteria established for the given tumor entity * Expressing at least one of the following HLA alleles:HLA-A1,-A2,-A3,-A24, and -B7 assessed by HLAgenotyping * ECOG performance status of <=1, estimated life expectancy of at least 3 months * Adequate hematological function defined by WBC >=3 x 10x9/L, lymphocyte count >=0.5 x 10x9/L, hemoglobin >=10 g/dL, platelet count >=100 x 10x9/L * Adequate blood coagulation parameters defined as aPTT and INR <= 1.5 x ULN * Adequate renal function defined by a serum creatinine <=2 x ULN * Adequate hepatic function defined by total bilirubin <=2 x ULN and AST and ALT levels <=2.5 x ULN (in subjects with liver metastases <=5 x ULN) * Effective contraception for female and male subjects if the risk of conception exists Exclusion Criteria: * Treatment in another clinical study within the past 30 days prior to the first administration of study treatment * Previous treatment with an investigational anticancer vaccine * Requirement of concurrent treatment with a nonpermitted drug * Active significant autoimmune disease (with the exception of vitiligo) * Receipt of allogeneic stem cell transplantation * Significant acute or chronic infections (e.g. viral hepatitis, HIV) * Primary brain tumors and brain metastases (with the exception of brain metastases that are stable after irradiation or surgically resected brain metastases if subjects have been asymptomatic for >=6 months) * Rapidly progressive disease (e.g. tumor lysis syndrome) * Radiotherapy, chemotherapy, surgery (excluding prior diagnostic biopsy), immunotherapy or any investigational drug within 30 days before the start of study treatment * Pregnancy or lactation * Active drug or alcohol abuse * Known hypersensitivity to the study treatment or any of its components * Any significant disease that, in the Investigator's opinion, should exclude the subject from the study; for questions about this criterion, the Investigator should contact the sponsor. * Persisting toxicity related to prior therapy >=grade 2 National Cancer Institute-Common Terminology Criteria For Adverse Events version 3.0 * Legal incapacity or limited legal capacity

NCT_ID NCT01012102

Study_NameEMD 640 744 in Montanide ISA 51 VG Administered in Subjects With Advanced Solid Tumors

Study Objectives This is an open-label, two-part, multicenter study to evaluate the safety and tolerability of DS-8201a in participants with advanced solid malignant tumors. Conditions: Advanced Solid Tumors Intervention / Treatment: DRUG: DS-8201a (DP1), DRUG: DS-8201a (DP2), DRUG: DS-8201a (DP) Location: Japan, United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: * Eastern Cooperative Oncology Group performance status( PS) of 0 or 1. * Left Ventricular Ejection Fraction (LVEF) >= 50% Part 1: * Advanced/unresectable or metastatic breast cancer or gastric or gastroesophageal junction adenocarcinoma that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. Part 2a: * Advanced breast cancer with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. * Treated with ado-trastuzumab emtansine (T-DM1) Part 2b: * Advanced gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. * Treated with trastuzumab Part 2c: * Advanced breast cancer with HER2 low expression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. Part 2d: * Satisfy at least one of the following criteria 1. Advanced/unresectable or metastatic solid malignant tumor with HER2 expression other than breast cancer and gastric or gastroesophageal junction adenocarcinoma that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. 2. Advanced/unresectable or metastatic tumor with HER2 mutation that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. Part 2e: * Advanced breast cancer with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. * Treated with ado-trastuzumab emtansine (T-DM1) (patients with HER2 overexpression only) Exclusion Criteria: * Has a medical history of symptomatic Congestive Heart Failure (CHF) (NYHA classes II-IV) or serious cardiac arrhythmia. * Has a medical history of myocardial infarction or unstable angina. * Has a QTc prolongation to > 450 millisecond (ms) in males and > 470 ms in females. * Has a medical history of clinically significant lung diseases

NCT_ID NCT02564900

Study_NameStudy of DS-8201a in Subjects With Advanced Solid Malignant Tumors

Study Objectives The purpose of this study was to determine the effect of 0.5% amlexanox oral rinse compared to a vehicle control on mucositis-related ulceration and erythema (objective score)and on mucositis-related oral pain (subjective score). A secondary objective was to evaluate the safety of 0.5% amlexanox oral rinse by determining the frequency of treatment-emergent drug-related adverse events or clinical laboratory abnormalities. Conditions: Oral Mucositis Intervention / Treatment: DRUG: amlexanox, DRUG: Vehicle rinse Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Patient is 18 years or older; * Patient has a histologically documented diagnosis of cancer of the head and neck region; * Patient is about to receive a course of radiation therapy (with or without concomitant chemotherapy) with a planned dose of at least 60 Gy over 6 <= age <= 7 weeks, and with planned fields to involve at least 50% of the oral mucosa; This criterion was amended (Amendment 01 dated August 28, 2000) to read as follows: * Amended: Patient is at a high risk of developing radiation-induced mucositis. For the purpose of this study, high-risk patients will be defined as: * patients about to receive a course of radiation therapy (with or without concomitant chemotherapy) with a planned dose of at least 60 Gy over 6 <= age <= 7 weeks, and * with planned fields to involve at least 40% of the oral and oropharyngeal mucosa visible by direct inspection; 4. Patient has a Karnofsky Performance Scale (KPS) score of 60% or more; 5. Patient is willing and able to cooperate with the protocol including rinsing of the oral cavity with the investigational or vehicle oral rinse 6 times per day. 6. The patient or guardian is capable of providing informed consent. 7. If female, the subject has undergone a urine pregnancy test with negative results, and has agreed to practice effective methods of contraception for the duration of the study. Exclusion criteria 1. Patient has had previous radiation therapy to the oral mucosa; 2. Patient is about to receive hyperfractionated radiation therapy; 3. Patient has active oral H. simplex lesions, oral candidiasis, or oral mucositis due to other disease processes; 4. Patient has uncontrolled infection; 5. Patient has HIV, Hepatitis B (HBV) (as measured by HBs-Ag) or Hepatitis C (HCV) infection; 6. Patient has not recovered from oral toxicity attributable to prior treatment; 7. Patient has abnormal laboratory values that meet the following criteria: * Serum creatinine greater than 2 x upper limit of normal * Total bilirubin greater than 3 x upper limit of normal; * SGOT greater than 3 x upper limit of normal; * LDH greater than 3 x upper limit of normal; 8. Patient has known sensitivities to any of the study preparation ingredients; 9. Patient has participated in a clinical research study within the last 30 days prior to enrollment; 10. Patient is unable to communicate or cooperate with the investigator due to language problems, poor mental development, or other reasons.

NCT_ID NCT01083875

Study_NameStudy to Determine the Effects Treatment With Amlexanox 0.5% Oral Rinse Solution on Oral Mucositis Associated With Radiation Therapy for Cancer of the Head and Neck Region

Study Objectives The purpose of this study is to evaluate the usefulness of fentanyl matrix by assessing patients' satisfaction when administrating fentanyl matrix, a background pain treatment, and a breakthrough pain treatment to lung cancer patients who complain of pain. Fentanyl matrix is designed to deliver medication at a nearly constant amount per unit time into the body through the skin for 3 days (72 hours). Conditions: Lung Cancer, Pain Intervention / Treatment: DRUG: fentanyl matrix Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with histologically confirmed lung cancer, who complain of cancer pain * Patients who are taking Ultracet, Tramadol, or Codeine (or Codeine combination drug) for cancer pain-relief purposes, but still complain of a pain level of 4 or above on the Numeric Rating Scale (NRS) during the past 24 hours: Ultracet 3 tablets/day, Tramadol 150 mg/day, Codeine 200 mg /day, or Codeine combination less than 3 capsules/day * Patients who are able to communicate with the investigator about his/her pain * Patients who use proper contraceptives during the study period if they are women of childbearing potential * Patients whose life expectancy is 3 months or longer * Patients who have signed an informed consent form Exclusion Criteria: * Patients participating in other clinical trials * Patients with a history of hypersensitivity to opioid analgesics * Patients with a history of drug abuse * Patients who are unable to use a transdermal product due to skin disease * Patient with a history of CO2 retention (e.g. chronic obstructive pulmonary disease) * Patients who are receiving radiotherapy or chemotherapy when registering for the study or who plan to receive it during the study * Patient who are pregnant or are of childbearing potential and not using contraceptives

NCT_ID NCT01060137

Study_NameFentanyl Matrix in Lung Cancer Pain

Study Objectives The purpose of the study is to determine the dose of the combination of trabectedin (Yondelis) and Doxorubicin for which neutropenia (low white blood cell counts) could be managed with filgrastim (a Granulocyte-Colony Stimulation Factor that is used to help control neutropenia) in patients with a type of cancer called soft tissue sarcoma. Conditions: Soft Tissue Sarcoma, Sarcoma, Neoplasms, Connective and Soft Tissue, Neoplasms by Histologic Type, Neoplasms Intervention / Treatment: DRUG: Doxorubicin, DRUG: Trabectedin, DRUG: Dexamethasone Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Have a diagnosis of soft tissue sarcoma, recurrent or persistent * Signed informed consent obtained for all patients before performing any study-related procedures Exclusion Criteria: * Patients treated with more than 1 prior chemotherapy regimen (including adjuvant (or other additional) therapy) * Previous exposure to anthracyclines (a class of drugs used in cancer chemotherapy, example is Doxorubicin) or trabectedin * Less than 4 weeks since radiation therapy * Known metastases (spread) of cancer to the central nervous system * Other ongoing serious illness present at the time of enrollment as determined by the Investigator

NCT_ID NCT00102609

Study_NameA Safety Study Utilizing Yondelis and Doxorubicin in Patients With a Type of Cancer Called Soft Tissue Sarcoma

Study Objectives This single-blind, randomized controlled trial studies how well inhaled essential oils work for common quality of life concerns in patients who are undergoing cancer treatment such as chemotherapy, targeted therapy, and/or immunotherapy given through the vein (intravenously). Aromatherapy using essential oils, such as ginger essential oil, German chamomile essential oil, and bergamot essential oil, may improve quality of life issues such as nausea, anxiety, loss of appetite, and fatigue in patients undergoing treatment for cancer. Conditions: Gastrointestinal Cancer, Neuroendocrine Carcinoma, Skin Cancer Intervention / Treatment: PROCEDURE: Aromatherapy and Essential Oils, PROCEDURE: Aromatherapy and Essential Oils, PROCEDURE: Aromatherapy and Essential Oils, PROCEDURE: Aromatherapy and Essential Oils, OTHER: Subject Diary Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * Gastrointestinal cancers, neuroendocrine cancer, or melanoma or other skin cancers * Receiving chemotherapy, targeted therapy, and/or immunotherapy * Not naive to the treatment * Must be able to read and write English Exclusion Criteria: * Allergies to ragweed, chrysanthemum, chamomile, ginger, bergamot, citrus fruits, tree nuts, perfumes * Asthma diagnosis * Patients receiving only octreotide injections * Patients receiving floxuridine (FUDR) via hepatic artery infusion (HAI) pump only

NCT_ID NCT03858855

Study_NameInhaled Essential Oil Effect on Common QOL Concerns During Cancer Treatment

Study Objectives The goal of this clinical research study is to evaluate the effectiveness of Avastin® in combination with docetaxel and carboplatin in the treatment of lung cancer. The safety of this combination will also be studied. Conditions: Non-Small Cell Lung Cancer Intervention / Treatment: DRUG: Bevacizumab (Avastin), DRUG: Carboplatin, DRUG: Docetaxel Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Men and women, at least 18 years, with histologically confirmed, advanced stage IIIB or IV NSCLC for whom no curative options exist and for whom docetaxel and carboplatin is a reasonable treatment option; * At least 1 target lesion that is unidimensionally measurable as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) and has not been previously irradiated; * Eastern Cooperative Oncology Group Performance Status of 0 or 1, (determined within 2 weeks prior to receiving study medication; * Ability to understand and adhere to the protocol requirements, and give informed consent * Use of effective means of contraception (men and women) in subjects of child-bearing potential. Child-bearing potential is defined as follows: A woman of childbearing potential is a sexually mature woman who has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses at any time in the preceding 12 consecutive months). Exclusion Criteria: * Patients who have had docetaxel in nonradiosensitizing therapy * Patients who have received prior full dose systemic chemotherapy for NSCLC (ie neoadjuvant, adjuvant, or metastatic) within the last 6 months. * Eastern Cooperative Oncology Group (ECOG) status of 2 or greater * Screening clinical laboratory values:*absolute neutrophil count (ANC) of <1,500/µL *Platelet count of <75,000/µL * international normalized ratio (INR) >= 1.5 *T bilirubin elevation above normal (MDACC upper normal limit is 1.0 mg/dL) *Serum creatinine of >2.0 mg/dL *Hemoglobin of <9 mg/dL (may be transfused or receive epoetin alfa [e.g., Epogen®] to maintain or exceed this level) *The pt is ineligible if: 1.alk phos>5xULN; 2.AST or ALT >5xULN; 3.alk phos >1xULN but <= 2.5xULN AND AST or ALT >1.5xULN but <=5xULN;4.alk phos >2.5xULN but <=5xULN AND AST or ALT > 1xULN but<= 1.5xULN; 5.alk phos >2.5xULN but<=5xULN AND AST or ALT >1.5xULN but <=5xULN * Inability to comply with study and/or follow-up procedures * History of other disease, active infection, metabolic dysfunction , physical examination finding, or clinical laboratory finding which is uncontrolled requiring medical intervention giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications. * Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a bevacizumab cancer study * Prior exposure to anti-VEGF therapy * Blood pressure of > 140/90 mmHg as documented in two consecutive blood pressure readings within 4 hours * Any prior history of hypertensive crisis or hypertensive encephalopathy * New York Heart Association (NYHA) Grade II or greater congestive heart failure * History of myocardial infarction or unstable angina within 6 months * History of stroke or transient ischemic attack within 6 months * Significant vascular disease (e.g., aortic aneurysm, aortic dissection) * Evidence of bleeding diathesis or coagulopathy * Presence of central nervous system or brain metastases at any time * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study * Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0 * Pregnant (positive pregnancy test) or lactating * Proteinuria at screening as demonstrated by either: Urine protein:creatinine (UPC) ratio > 1.0 at screening OR Urine dipstick for proteinuria > 2+ (patients discovered to have > 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate < 1g of protein in 24 hours to be eligible). * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0 * Serious, non-healing wound, ulcer, or bone fracture * Lung carcinoma of squamous cell histology or any histology in close proximity to a major vessel, cavitation. * History of hemoptysis (bright red blood of 1/2 teaspoon or more) * Full dose anticoagulation, chronic use of Aspirin (>325 mg/day) or NSAIDs * Inability to comply with study and/or follow-up procedures

NCT_ID NCT00271505

Study_NameAvastin/Docetaxel/Carboplatin in Non-Small Cell Lung Cancer