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Study Objectives The purpose of this study is to examine the safety and toleration of PEP005 Topical Gel, administered on an actinic keratosis (AK) treatment area on the top of a hand. Conditions: Actinic Keratosis Intervention / Treatment: DRUG: PEP005 gel 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: * Male patients at least 18 years of age. * Post-menopausal female patients * 4 to 8 clinically typical, visible and discrete AK lesions within an area on the dorsum of one hand. * Written informed consent has been obtained. * Agreement from the patient to allow photographs of the selected AK treatment area to be taken and used as part of the study data package.

Study Objectives Current research suggests that diets rich in multiple food types (such as broccoli, onions and garlic) are beneficial to our health and may reduce the risk of some cancers, including prostate cancer. The purpose of this study is to investigate the relationship between ingestion of the bioactive compounds from broccoli and garlic, and prostate metabolism. Conditions: Prostate Cancer Intervention / Treatment: DIETARY_SUPPLEMENT: Allin, DIETARY_SUPPLEMENT: Sulforaphane, DIETARY_SUPPLEMENT: Placebo Location: United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Scheduled for template biopsy of the prostate as part of routine investigation or staging for prostate cancer at the Norfolk and Norwich University Hospital * BMI between 19.5 and 35 kg/m2 * Smokers and non-smokers Exclusion Criteria: * Those regularly taking 5α-reductase inhibitors or testosterone replacement medicines * Those on warfarin treatment * Those diagnosed with diabetes * Those diagnosed with or suspected to be high-risk for human immunodeficiency virus (HIV) and/or viral hepatitis * Those allergic to any of the ingredients included in the supplements (including those with lactose intolerance) * Those taking additional dietary supplements or herbal remedies that could affect the study outcome. * Those that are unable to understand English or give informed consent * Parallel participation in another research project that involves dietary intervention * Any person related to or living with any member of the study team.

Study Objectives Determine the pharmacokinetic interactions between rapamycin and sunitinib in patients with advanced solid tumors. Conditions: Solid Tumors Intervention / Treatment: DRUG: sunitinib, DRUG: rapamycin Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: EARLY_PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Metastatic or unresectable cancer for which standard treatments do not exist or are no longer effective or cancers where evidence of efficacy of single agent sunitinib or single agent mTOR inhibitor has been demonstrated * Measurable or non-measurable disease. * No prior treatments for 4 weeks before starting study * No ongoing toxicities from previous treatments * >= 18 years * Performance status 2 or better * Life expectancy of at least 3 months. * Normal organ and marrow function as defined below: * No transfusions of packed red blood cells within 1 week of starting treatment. A hemoglobin of 9.0 g/dL or greater is recommended. Patients should not be transfused for protocol participation. * Leukocytes greater than or equal to 3,000/μL * Absolute neutrophil count greater than or equal to 1,500/μL * Platelets greater than or equal to 100,000/μL * Total bilirubin less than or equal to 1.5 x ULN * AST and ALT less than or equal to 2.5x ULN (less than or equal to 5x ULN if liver function abnormalities are due to underlying disease) * Creatinine within normal institutional limits OR * Creatinine clearance > 60 mL/min/1.73 m2 * PT or INR within normal institutional limits * Serum calcium within normal institutional limits * QTc < 500 msec. * Patients with prior anthracycline exposure or that have received central thoracic radiation must have NYHA class I cardiac function * Must agree to use adequate birth control * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * Prior treatments within 4 weeks (6 weeks for nitrosoureas or mitomycin C) of entering the study or those who have not recovered from adverse events due prior treatments * Current treatment with other investigational agents. * Prior therapy with a VEGFR or mTOR inhibitor * History of allergic reactions attributed to compounds of similar chemical or biologic composition to rapamycin or sunitinib. * QTc prolongation (QTc interval equal to or greater than 500 msec) or other significant ECG abnormalities * Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements. * Patients with any of the following conditions are excluded: * Serious or non-healing wound, ulcer, or bone fracture. * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment. * Known active infection * Major surgery or radiation therapy within 4 weeks of starting the study treatment. * NCI CTCAE Version 3.0 grade 3 hemorrhage within 4 weeks of starting the study treatment. * History of CVA or transient ischemic attack within 12 months prior to study entry. * History of myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry. * History of pulmonary embolism within the past 12 months. * Class III or IV heart failure as defined by the NYHA functional classification system * Ongoing cardiac dysrhythmias * Poorly controlled hypertension (systolic blood pressure of 140 mmHg or higher or diastolic blood pressure of 90 mmHg or higher) * Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication * History of interstitial lung disease * Patients with severe immunodeficient states (as judged by the treating physician) * Pregnancy or breastfeeding. * HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for interactions with the study drugs * Use of certain medications (as determined by the investigator) * Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk or interfere with the study

Study Objectives This is a single-arm, multi-centre, phase II study in biliary tract cancer (BTC) patients. The main objective is to detect an increase in progression-free survival rate at 6 months (according to RECIST version 1.1) from 60% in patients with BTC treated with standard chemotherapy (CT) approach to 75% when treated with CT combined with pembrolizumab. Conditions: Biliary Tract Cancer, Metastatic Cancer, Advanced Cancer, Gallbladder Cancer Intervention / Treatment: DRUG: Pembrolizumab, DRUG: Cisplatin, DRUG: Gemcitabine Location: Spain, United Kingdom, Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * A histopathological / cytological diagnosis of non-resectable or recurrent / metastatic biliary tract carcinoma (intra- or extra-hepatic) or gallbladder * Availability of archival FFPE tumor tissue for biobanking * Measurable disease by CT/MRI (RECIST 1.1) within 28 days of enrollment * ECOG performance status 0, 1 * Age >= 18 with estimated life expectancy >3 months * Adequate hematological function: screening labs should be performed within 14 days (± 3 days) prior to enrollment: * Hemoglobin >= 10 g/dl* (prior transfusions for patients with low hemoglobin are allowed) * White blood cell (WBC) >= 3.0 x 109/L * Absolute neutrophil count (ANC) >= 1.5 x 109/L * Platelet count >= 100 x 109/L * Adequate liver function: screening labs should be performed within 14 days (± 3 days) prior to enrollment: * Total bilirubin <= 1.5 x upper limit of normal (ULN) * ALT and/or AST & alkaline phosphatase <= 5 x ULN * Adequate renal function: screening labs should be performed within 14 days (± 3 days) prior to enrollment: * Serum creatinine < 1.5 x ULN * and a calculated GFR >= 45 mL/min (using Cockcroft-Gault formula). If the calculated GFR is below 45 mL/min, isotope EDTA confirmation of adequate renal function is required (see Appendix F). If isotope EDTA methods are not available, then a 24-hour urine creatinine clearance can be used. * Adequate coagulation: screening labs should be performed within 14 days (± 3 days) prior to enrollment: * International Normalized Ratio (INR) or Prothrombin Time (PT): <= 1.5xULN unless patient is receiving anticoagulant therapy as long as PT or Partial Thromboplastin Time (PTT) is within therapeutic range of intended use of anticoagulants * Adequate biliary drainage with C-reactive protein (CRP) levels in normal ranges (based on institution's standard): screening labs should be performed within 14 days (± 3 days) prior to enrollment * Patient is not currently participating and receiving study therapy or has not participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks prior to enrollment * Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 72 hours prior to the first dose of study treatment. * Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly. Such methods include: * Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) * Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) * Intrauterine device (IUD) * Intrauterine hormone-releasing system (IUS) * Bilateral tubal occlusion * Vasectomised partner * Sexual abstinence. Note: abstinence is acceptable if this is established and preferred contraception for the patient and is accepted as a local standard. * Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 120 days after the last study treatment. * Before patient enrollment, written informed consent must be given according to ICH/GCP, and national/local regulations. Exclusion Criteria: * Patients with ascites grade 2 or higher * Child Pugh B or C hepatic impairment * Incomplete recovery from previous surgery or unresolved biliary tract obstruction * Active infection requiring therapy. Antibiotic treatment should have been completed 5 days before enrollment * Patients who are candidates for curative surgery * History of (non-infectious) pneumonitis that required steroids or current pneumonitis. No history of or current interstitial lung disease * Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment * Diagnosis of immunodeficiency, systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment * Known history of human immunodeficiency virus (HIV), active Hepatitis B or Hepatitis C * Patients with hyperthyroidism or hypothyroidism unless stable on hormone replacement * History of another malignancy or a concurrent malignancy. Exceptions include patients who have been disease-free for 5 years, or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example cervical cancer in situ. * Patients who received treatment with live vaccines within 30 days prior to the first dose of study medication. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, seasonal flu, H1N1 flu, rabies, BCG and typhoid vaccine. * Prior treatment with any anti-CTLA4 monoclonal antibody or anti-PD-1, or PD-L1 or PD-L2 agent. Examples of PD-1 inhibitors (include, but are not limited to): pembrolizumab (Merck); Nivolumab (also known as BMS-936558, MDX-1106, ONO-4538) (Bristol-Myers Squibb); Pidilizumab (CT-11) (Cure-Tech/Teva); and AMP-224 (Amplimmune). Examples of PD-L1 inhibitors (include, but are not limited to): BMS-936559 (also known as MDX-1105) (Bristol-Myers Squibb); MPDL3280A (also known as RG7446) (Roche Genentech); and MEDI4736 (MedImmune). * Prior systemic chemotherapy for locally advanced or metastatic disease. * Prior adjuvant chemotherapy is allowed if the last treatment was completed at least 6 months before trial entry and neither gemcitabine nor cisplatin were given. Also the following treatment modalities are allowed within the rules described (provided there has been a full recovery): * Surgery - patients may have undergone a non-curative operation (i.e. R2 resection [with macroscopic residual disease] or palliative bypass surgery only). Patients who have previously undergone curative surgery, must have evidence of non-resectable disease relapse requiring systemic chemotherapy prior to study entry. * Radiotherapy - patients may have received prior radiotherapy (with or without radiosensitising low-dose chemotherapy) for localised disease. However, there must be clear evidence of disease progression prior to inclusion in this study. * Photodynamic therapy (PDT) for localized disease only with no evidence of metastatic disease - patients may have received prior PDT, provided the patient has fully recovered and at least 28 days have elapsed since the PDT and there is clear evidence of disease progression at the local site or disease or at a new metastatic site. * PDT for localised disease to relieve biliary obstruction in the presence of metastatic disease - patients may have received prior PDT provided the patient has fully recovered and at least 28 days have elapsed since the PDT. Patients may enter trial provided the non-PDT treated lesion(s) only are followed for response assessment. * Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before enrollment in the trial.

Study Objectives Based on the evidence acquired in the post-menopausal setting with everolimus and on pre-clinical evidences supporting the investigation of PI3K inhibitors, such as alpelisib and buparlisib, in combination with endocrine therapy in hormone receptor-positive MBC, the purpose of this phase Ib trial is to assess the maximum tolerated dose (MTD) and/or the RP2D(s), to characterize the safety and tolerability, to determine the single and multiple dose PK profile and assess the preliminary anti-tumor activity of alpelisib and buparlisib in combination with tamoxifen plus goserelin acetate in premenopausal hormone receptor-positive advanced breast cancer patientsgroup. Conditions: Pre-menopausal Breast Cancer, PI3K Pathway Inhibition Intervention / Treatment: DRUG: alpelisib (BYL719), DRUG: buparlisib (BKM120) Location: Thailand, Korea, Republic of, Taiwan, Hong Kong Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patient has histologically and/or cytologically confirmed diagnosis of breast cancer * Patient has radiological or objective evidence of inoperable locally advanced or metastatic breast cancer * Patient has HER2-negative breast cancer (based on most recently analyzed tumor sample) * Patient has ER positive and/or PgR positive breast cancer by local laboratory testing * Patient is premenopausal. Premenopausal status is defined as either: 1. patient had last menstrual period within the last 12 months, OR 2. if on tamoxifen within the past 3 months, with a plasma estradiol >=10 pg/mL and FSH <=40 IU/l or in the premenopausal range, according to local laboratory definition , OR 3. in case of chemotherapy induced amenorrhea, with a plasma estradiol >=10 pg/mL) and/or FSH <=40 IU/l or in the premenopausal range according to local laboratory definition. * Patient has no previous history of endocrine therapy in the metastatic setting. Note: * Patients who received oral endocrine therapy with duration less than 3 weeks or <=1 injection of LHRH agonist and discontinued for a reason other than suspicious or evidence of disease progression are eligible * Adjuvant treatment with tamoxifen monotherapy and LHRH analogue monotherapy is allowed. Patients who received tamoxifen plus LH-RH agonist/antagonist in the adjuvant setting are eligible provided they start investigational treatment at least 12 months after the last dose of tamoxifen or LH-RH agonist/antagonist, whichever came later. * Patients who were already established on bisphosphonate therapy may continue on bisphosphonates. * Patient has received <=1 prior chemotherapy line for MBC * For patient who received prior systemic therapy, radiological or objective evidence of recurrence or progression on or after the last systemic therapy is needed * Patient must have as per RECIST 1.1: * measurable disease or * non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease. * Patient has adequate bone marrow and organ function as defined by the following laboratory values: * Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≦ 2 which the investigator believes is stable at the time of screening. * Patient has negative serum pregnancy test (β-hCG) within 72 hrs before starting study treatment. Exclusion criteria * Patient is post-menopausal. * Patient has received previous endocrine treatments in the metastatic setting. * Patient has received previous treatment with PI3K inhibitors, AKT inhibitors, mTOR inhibitors * Patient has received more than one chemotherapy line for metastatic disease * Patient has symptomatic CNS metastases * Patient who has received wide field radiotherapy ≦ 4 weeks or limited field radiation for palliation ≦ 2 weeks prior to starting study drug or who have not recovered to grade 1 or better from related side effects of such therapy (with exception of alopecia alopecia) * Patient has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy * Patient is currently receiving increasing or chronic treatment (> 5 days) with corticosteroids or another immunosuppressive agent, as chronic administration of corticosteroids (> 5 days) can induce CYP3A4 * Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed * Patient is currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP3A. The patient must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the treatment phase is initiated. * Patient has a score ≧ 12 on the PHQ-9 questionnaire * Patient selects a response of "1, 2 or 3" to question number 9 on the PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9) * Patient has a GAD-7 mood scale score ≧ 15 * Patient has a medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others) or patients with active severe personality disorders (defined according to DSM- IV) are not eligible. * Patient has ≧ Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety * Patient has active cardiac disease or a history of cardiac dysfunction * Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) * Patient has any of the following cardiac conduction abnormalities 1. Ventricular arrhythmias except for benign premature ventricular contractions 2. Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication 3. Conduction abnormality requiring a pacemaker 4. Other cardiac arrhythmia not controlled with medication 5. Patient has a QTcF > 480 msec on the screening ECG (using the QTcF formula) * Patient is currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to treatment start. * Patient has chronic pulmonary disease including dyspnea at rest from any cause or with interstitial lung disease.

Study Objectives Transurethral resection of the prostate (TURP) represents the gold standard in the operative management of benign prostatic hyperplasia (BPH) and the transurethral resection of bladder tumor (TURBT) is the first-line surgical treatment for bladder tumors. One of the most important complications of urological endoscopic resections is intraoperative and postoperative bleeding requiring blood transfusion. Allogeneic blood transfusion is not free of risks, like infection transmission, hemolytic reactions, transfusion-related lung injury, fluid overload, increased costs and hospital length of stay. Tranexamic acid (TXA) is a synthetic analog of serin than reversibly inhibits fibrinolysis by blocking lysine union sites in the plasmin and plasminogen activator molecules. TXA has been used to reduce blood loss and the need for allogeneic blood transfusion in cardiac surgery and orthopedic surgical procedures but few studies have assessed the efficacy of this antifibrinolytic agent in urological endoscopic procedures. The investigators designed this double-blind, placebo controlled study evaluate the safety and efficacy of the antifibrinolytic agent tranexamic acid in reducing blood transfusion in patients undergoing endoscopic surgery in urology. Conditions: Hemorrhage Intervention / Treatment: DRUG: Tranexamic Acid, DRUG: Placebo Location: Tunisia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: TRIPLE

Inclusion Criteria: * Adult (>=18) * male or female * Undergoing elective TURP or TURBT * Spinal anesthesia * Subject is American Society of Anesthesiologists (ASA) physical status 1 or 2. Exclusion Criteria: * Atrial fibrillation * Coronary artery disease treated with drug eluting stent * Severe chronic renal failure * Congenital or acquired thrombophilia * Known or suspected allergy to tranexamic acid.

Study Objectives This is an international,multicenter, prospective, open, double randomised and controlled phase III study to compare the therapeutic efficacy of tandem high dose Melphalan versus triple intermediate dose Melpahaln in newly-diagnosed myeloma patients Conditions: Multiple Myeloma Intervention / Treatment: DRUG: Melphalan Location: Austria Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patients with newly diagnosed multiple myeloma of either IgG, IgG, IgD, IgE, IgM (but excluding Waldenstöm´s macroglobulinemia) lambda of kappa light chain, low-secretory, non-secretory disease or plasma cell leukemia * Performance status of 0, 1, 2, or 3 * Patients not pre-treated with cytostatic drugs * Patients who clearly require treatment (usually Durie and Salmon stage II or III) * Patients in stage I who are symptomatic and/or show progression of their disease * Patients must have an anticipated life expectancy of at least 3 months * Patients must have adequate organ function * Patients must have had a minimum recovery period of 2 weeks following any major surgical procedure before entry into this study * Patients must be between 19 and 70 years of age, also it is understood that most of the patients above 65 will not be eligible because of poor performance status or multimorbidity * Women of childbearing potential must have a negative pregnancy test and must take adequate precautions to prevent pregnancy during treatment * Patients must have signed an informed consent Exclusion Criteria: * Patients with more than 3 irradiation fields * Patients presenting initially with one of the following conditions: * Extramedullary plasmacytoma or solitary plasmacytoma * Monoclonal gammopathy of undetermined significance * Smouldering myeloma * Patients with an irreversible performance status of 4 * Medical of psychiatric conditions that compromise the patient´s ability to give informed consent or complete the study * Patients with congestive heart failure, NYHA III, IV * Known HIV positivity * Known intolerance to any of the study drugs or components * Acute infection requiring systemic antibiotics at study entry until fully resolved * Patients with any underlying medical condition which cannot be adequately controlled * Patients with second primary malignancies (with the exception of cervical carcinoma in situ and non-melanoma skin malignancies) are not eligible unless the patient has been disease-free for at least five years

Study Objectives The ATR (ataxia-telangiectasia and Rad3 related protein) inhibitor BAY1895344 is developed for the treatment of patients with advanced solid tumors and lymphomas. The purpose of the proposed trial is to evaluate the safety and tolerability of BAY1895344, and to identify the maximum tolerated dose of BAY1895344 that could be safely given to cancer patients. Further, the response of the cancer to the treatment will be determined. Conditions: Advanced Solid Tumor, Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma Intervention / Treatment: DRUG: Elimusertib (BAY1895344) Location: Canada, Japan, Switzerland, United Kingdom, United States, Singapore, China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: Part A - single-agent dose-escalation: * Patients with histologically confirmed solid tumors or NHL. Patients with tumors known to be positive for deoxyribonucleic acid damage repair (DDR) defects (such as ataxia-telangiectasia mutated [ATM] deleterious mutation or low ATM expression) can be included. J-arm of Part A - single-agent dose-escalation in Japanese: * Japanese patients with histologically confirmed solid tumors. Patients with tumors known to be positive for DDR defects (such as ATM deleterious mutation or low ATM expression) can be included. Part A.1 - single-agent dose-escalation with alternative dosing schedule: * Patients with histologically confirmed solid tumors or NHL known to be positive for ATM loss and/or ATM deleterious mutations will be included. The biomarker status of patients in Part A.1 will be evaluated before general screening and only patients with the presence of the putative biomarkers of DDR deficiency will be recruited into general screening. Part B - single-agent expansion: * Patients with DDR deficiency biomarker-positive advanced solid tumors of the following histologies: i) CRPC; ii) HER2-negative BC that is hormone-receptor positive (estrogen-receptor positive, progesterone-receptor positive, or both) or TNBC; iii) CRC, and iv) gynecological tumors (ovarian, primary peritoneal, and fallopian tube cancers, endometrial cancer, or cervical cancer). * Patients with histologically confirmed advanced solid cancer, regardless of the cancer type, or NHL and loss of ATM protein by IHC. * The biomarker status of patients in Part B will be evaluated before general screening and only patients with the presence of the putative biomarkers of DDR deficiency will be recruited into general screening. Part A.1 And Part B: * Patients must be able to provide either samples of archival tumor tissue not older than 6 months or a fresh tumor biopsy during general screening. Part B.1 - single-agent expansion with alternative dosing schedule: * Patients with histologically confirmed R/R MCL. These patients do not undergo biomarker testing to determine eligibility. The provision of baseline tumor tissue (archival or fresh) is strongly encouraged. If archival tissue <= 6 months old is unavailable, a fresh baseline biopsy may be obtained if safe and feasible. The following inclusion criteria apply to ALL (dose-escalation and expansion) patients: * Patients with tumors resistant or refractory to standard treatment and in which, in the opinion of the investigator, experimental treatment with BAY1895344 may be of benefit. Furthermore, no standard therapy would confer clinical benefit to the patient. Patients in the MCL cohort of Part B.1 are to be relapsed or refractory to standard treatments. * Patients must have measurable disease (as per Response Evaluation Criteria in Solid Tumors, version 1.1 [RECIST 1.1] or the Lugano classification as applicable, with the exception of prostate cancer patients who must have measurable or evaluable disease per the recommendations of the Prostate Cancer Clinical Trial Working Group 3 [PCWG3]). * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. For MCL patients: ECOG of 0 to 2. * Patients must have adequate bone marrow function as assessed by the following laboratory tests to be conducted within 7 (+2) days before the first dose of study drug. Note that the below values are to be independent of red blood cell transfusions or granulocytes colony-stimulating factor (G-CSF) (i.e., no red blood cell or platelets transfusion within 28 days prior to the screening complete blood count [CBC] result, or administration of G-CSF is to occur within 14 days prior to the CBC result). Requirements for MCL patients are indicated below. * a. Hemoglobin >= 9 g/dL. Patients with chronic erythropoietin treatment consistent with institutional guidelines can be included. For MCL patients: >= 8 g/dL; red blood cell transfusions during the screening period are allowed, and patients with chronic erythropoietin treatment consistent with institutional guidelines can be included * b. Absolute neutrophil count (ANC) >= 1.5 X 10^9/L (>= 1500/mm^3). For MCL patients: ANC >= 1.0 X 10^9/L. Patients with ANC <= 1.0 X 10^9/L due to marrow infiltration may receive G-CSF during screening to bring pretreatment ANC levels to >= 1.0 X 10^9/L * c. Platelet count >= 100 X 10^9/L (>=100,000/mm^3). For MCL patients: >= 75 X 10^9/L Exclusion Criteria: * Known hypersensitivity to the study drugs or excipients of the preparations or any agent given in association with this study * History of cardiac disease: congestive heart failure New York Heart Association (NYHA) class >II, unstable angina (angina symptoms at rest), new-onset angina (within the past 6 months before study entry), myocardial infarction within the past 6 months before study entry, or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers, calcium channel blockers, and digoxin are permitted) * Moderate or severe hepatic impairment, i.e. Child-Pugh class B or C * Known human immunodeficiency virus (HIV)-infected persons are not eligible if any of the following criteria apply： * CD4+ T-cell count less than 350 cells/μL * History of AIDS-defining opportunistic infection within the past 12 months * On established antiretroviral therapy (ART) for less than 4 weeks or presenting with a viral load of more than 400 copies/mL prior to enrollment * On ART or prophylactic antimicrobials that are expected to cause significant drug-drug interactions or overlapping toxicities with study intervention * Patients who have an active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection requiring treatment. Patients with chronic HBV or HCV infection are eligible at the investigator's discretion provided that the disease is stable and sufficiently controlled under treatment. * Infections of Common Terminology Criteria for Adverse Events Version (CTCAE) Grade 2 not responding to therapy or active clinically serious infections of CTCAE Grade > 2 * Metastatic solid brain, spinal, or meningeal tumors or central nervous system (CNS) lymphoma manifestations (including meningeosis lymphomatosa and parenchymal lymphoma lesions) unless the patient is > 3 months from definitive therapy, has a stable imaging study within 4 weeks prior to the first dose of study drug and is clinically stable with respect to the tumor at the time of study entry. Patients with asymptomatic brain metastases must not be on steroid therapy. Patients with neurological symptoms should undergo a CT / MRI scan of the brain or spinal column to exclude new or progressive brain, meningeal, or spinal metastases or CNS lymphoma manifestations. * History of organ allograft transplantation. For MCL patients: Those who received an allogeneic stem cell transplant may participate provided that engraftment has occurred, there is no evidence of GVHD, and the patient is not taking immune suppressants. MCL patients who received an autologous stem cell transplant may participate once they have recovered from the procedure. * Treatment with anticancer chemotherapy or immunotherapy during the study or within 3 weeks before the first dose of study drug. For small-molecule drugs, a period of at least 3 half-lives before the first dose of study drug is acceptable. Mitomycin C or nitrosoureas should not be given within 6 weeks before the first dose of study drug. * Treatment with systemic steroids (methylprednisolone dose >=10 mg/day or equivalent dose). For MCL patients: Treatment with systemic corticosteroids > 20 mg/day prednisone equivalent (unless patient has been taking a stable dose for >3 weeks and has shown tumor progression).

Study Objectives This phase II trial is studying how well giving bevacizumab together with lenalidomide and dexamethasone works in treating patients with relapsed or refractory stage II or stage III multiple myeloma. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Bevacizumab and lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Dexamethasone may stimulate the immune system in different ways and stop cancer cells from growing. Giving bevacizumab together with lenalidomide and dexamethasone may kill more cancer cells. Conditions: Multiple Myeloma in Relapse, Stage II Multiple Myeloma, Stage III Multiple Myeloma Intervention / Treatment: BIOLOGICAL: bevacizumab, DRUG: lenalidomide, DRUG: dexamethasone 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 symptomatic multiple myeloma: * Stage II or III disease * Relapsed or refractory disease after >= 2 courses of prior chemotherapy * Measurable levels of monoclonal protein (M protein) > 1.0 g/dL by serum protein electrophoresis OR > 200 mg of monoclonal light chain by 24-hour urine protein electrophoresis * Measurable bone disease, defined as >= 1 unidimensionally measurable lesion (longest diameter to be recorded) >= 20 mm with conventional techniques OR >= 10 mm with spiral CT scan (for patients with lytic bone disease) * No known brain metastases * ECOG performance status (PS) 0-2 OR Karnofsky PS 70-100% * Patients with PS of 3 are eligible if it is due to pain that is likely to improve with treatment * Life expectancy > 6 months * No known HIV positivity * No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months * No active infections requiring oral or intravenous antibiotics within the past week * No proteinuria (i.e., albuminuria) > 1,000 mg/24 hours unless related to the diagnosis of multiple myeloma * Patients with light chain (i.e., "Bence-Jones") proteinuria are still eligible if the non-light chain component of protein is < 1,000 mg/24 hours * No serious nonhealing wound or ulcer * No blood pressure > 150/90 mm Hg (even with medication) * No significant traumatic injury within the past 28 days * No clinically significant peripheral vascular disease * No evidence of bleeding diathesis or coagulopathy * No unstable angina or myocardial infarction within the past 6 months * No stroke within the past 6 months * No New York Heart Association class III or IV heart failure * No secondary malignancy within the past 2 years except squamous cell or basal cell carcinoma of the skin or carcinoma in situ of the cervix * Hemoglobin > 9 g/dL (may be supported by transfusion or growth factors) * WBC >= 2,000/mm^3 * Absolute neutrophil count >= 1,000/mm^3 * Platelet count >= 75,000/mm^3 * Bilirubin =< 2.5 mg/dL * At least 4 weeks since prior chemotherapy or radiotherapy and recovered * More than 7 days since prior minor surgical procedures, fine-needle aspirations, or core biopsies: More than 24 hours since prior bone marrow biopsy or central veinous access placement * More than 28 days since prior major surgical procedure or open biopsy * At least 4 weeks since prior and no concurrent participation in another experimental drug study * Prior autologous peripheral blood stem cell transplantation allowed * No prior lenalidomide * Concurrent full-dose anticoagulants allowed provided all of the following criteria are met: * No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices) * No thrombocytopenia requiring transfusion * Platelet count > 75,000/mm3 * INR 2-3 and stable * No concurrent major surgery * No concurrent sargramostim (GM-CSF) * No other concurrent investigational agents * No other concurrent anticancer agents or therapies * AST and ALT =< 5 times upper limit of normal * Creatinine < 2.5 mg/dL * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use 2 methods of effective contraception 4 weeks before, during, and 4 weeks after completion of study treatment * No history of allergic reactions attributed to compounds of similar chemical or biological composition to lenalidomide and/or bevacizumab or other agents used in the study

Study Objectives The primary objective of this study is to evaluate the safety of lenvatinib in HCC. Conditions: Carcinoma, Hepatocellular Intervention / Treatment: DRUG: Lenvatinib Location: India Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Males or females of >=18 years of age * Participant or their legally acceptable representative (LAR) is willing to sign written informed consent for participation in the study and ready to comply with the study procedures and schedule * Must have a confirmed diagnosis of unresectable HCC with one of the following criteria: * Histologically or cytologically confirmed diagnosis of HCC * Clinically confirmed diagnosis of HCC according to the American Association for the Study of Liver Diseases (AASLD) criteria, including cirrhosis of any aetiology or with chronic hepatitis B or C infection criteria * At least 1 measurable target lesion according to RECIST 1.1 meeting the following criteria: * Hepatic lesion: * The lesion can be accurately measured in at least one dimension as >=1.0 centimeter (cm) * The lesion is suitable for repeat measurement * Non-hepatic lesion: * Lymph node (LN) lesion that measures at least one dimension as >=1.5 cm in the short axis, except for porta hepatis LN that measures >=2.0 cm in the short axis * Non-nodal lesion that measures >=1.0 cm in the longest diameter * Lesions previously treated with radiotherapy or locoregional therapy must show radiographic evidence of disease progression to be deemed a target lesion * Participants are categorized to Stage B (not applicable for transarterial chemoembolization [TACE]) or Stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system. * Has adequate bone marrow function, defined as: * Absolute neutrophil count (ANC) >= 1.5*10^9 per liter (/L) * Haemoglobin >=8.5 gram per deciliter (g/dL) * Platelet count >=75*10^9/L * Adequate liver function based on liver function tests, defined as: * Albumin >=2.8 g/dL * Bilirubin less than or equal to <=3.0 milligram per deciliter (mg/dL) * Aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) <=5*the upper limit of normal (ULN) * Adequate blood coagulation function, defined as international normalized ratio (INR) <=2.3 * Adequate renal function, defined as >30 milliliter per minute (ml/min) calculated as per the Cockcroft and Gault formula * Adequately controlled blood pressure (BP) with 0 or 1 antihypertensive medications, defined as BP <=150/90 millimeter of mercury (mmHg) at screening and no change in antihypertensive medications within 1 week before Cycle 1 Day 1 * Adequate pancreatic function, defined as amylase and lipase <=1.5*ULN * With a Child-Pugh score A * With Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 * With life expectancy of >=12 weeks from the start of study treatment, as per Investigator's judgement. Exclusion Criteria: * With imaging findings for HCC corresponding to any of the following: * HCC with >=50% liver occupation * Clear invasion into the bile duct * Portal vein invasion at the main portal branch (Vp4) * Who have received any systemic chemotherapy, including sorafenib, or immunotherapy, or any systemic investigational anticancer agents for advanced/unresectable HCC * Who have received any anticancer therapy (including surgery, percutaneous ethanol injection, radio frequency ablation, transarterial [chemo] embolization, hepatic intra-arterial chemotherapy, biological, immunotherapy, hormonal, or radiotherapy) or any blood enhancing treatment (including blood transfusion, blood products, or agents that stimulate blood cell production, example granulocyte colony-stimulating factor [G-CSF]) within 28 days prior to enrolment * Who have not recovered from toxicities as a result of prior anticancer therapy, except alopecia and infertility * With significant cardiovascular impairment including but not limited to the history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within previous 6 months, or cardiac arrhythmia requiring medical treatment at the time of screening * With prolongation of corrected QT (QTc) interval to >480 millisecond (ms) * With gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib in the opinion of the Investigator * Bleeding or thrombotic disorders or use of anticoagulants such as, warfarin or similar agents requiring therapeutic international normalized ratio (INR) monitoring * Having a gastrointestinal bleeding event or active haemoptysis (bright red blood of at least 0.5 teaspoon) within 28 days prior to enrollment * With gastric or oesophageal varices that may require treatment * With any other active malignancy (except for HCC or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 36 months prior to enrolment * Any history of, or concurrent, brain or subdural metastases * Having >1 + proteinuria on urine dipstick testing will undergo 24 hour (h) urine collection for quantitative assessment of proteinuria. Patients with urine protein >=1 gram per 24 hour (g/24 h) will be excluded * With arterial-portal venous shunt or arterial-venous shunt preventing a proper diagnosis of the tumour * Any medical or other condition that in the opinion of the Investigator would preclude the participant's participation in the study. * With known intolerance to lenvatinib (or any of the excipients) * With positive human immunodeficiency virus (HIV) or active infection requiring treatment (except for hepatitis virus) * Who cannot be evaluated by either triphasic liver computed tomography (CT) or triphasic liver magnetic resonance imaging (MRI) because of allergy or other contraindication to both CT and MRI contrast agents * Have undergone major surgery within 3 weeks prior to the entry in the study or are scheduled for a surgery during the study period * Have already undergone a liver transplant * Female participants who are breastfeeding or pregnant at the time of enrolment in the study * Female participants of childbearing potential who, within 4 weeks prior to study enrolment, did not use a highly effective method of contraception or do not agree to use a highly effective method of contraception throughout the study period * Current abuse of alcohol; and current or past (last 12 months) abuse of drugs * Participation in a concurrent clinical trial or in another trial within the 6 months prior to this study enrolment

Study Objectives Surgical trauma initiates multiple physiological mechanisms that cause postoperative pain. Postoperative pain has nociceptive, inflammatory, and neuropathic components.Inadequate relief of postoperative pain leads to significant morbidity, delayed recovery, and mortality.Adverse reactions of medications used for postoperative pain management, particularly opioids, are common including pruritus and nausea and vomiting.Preemptive analgesia is defined as analgesic treatment that starts before surgical incision to prevent central sensitization caused by incisional and inflammatory injuries.Therefore, in this pilot study, the investigators are trying to evaluate safety and efficacy of preemptive multimodal analgesia compared with preemptive caudal analgesia and PCA morphine in pediatric cancer patient undergoing major abdominal surgery. Conditions: Pediatric Cancer, Pain, Postoperative Intervention / Treatment: DRUG: Paracetamol and ketamine, PROCEDURE: Caudal levobupivacaine, DRUG: Morphine Location: Egypt Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * were ASA I or II patients. * Aged between 5 and 12 years. * Both sexes. * Scheduled for major abdominal surgery with a midline incision. Exclusion Criteria: * included history of mental retardation or delayed development that may interfere with pain intensity assessment, * Known or suspected allergy to any administered drugs. * Active renal (creatinine clearance <50). * Hepatic (liver enzymes more than 10 folds). * Respiratory (SPO2 <92% on room air). * Cardiac disease (ejection fraction < 50%).

Study Objectives Phase III study of RAD001 adjuvant therapy in poor risk patients with Diffuse Large B-Cell Lymphoma (DLBCL) of RAD001 versus matching placebo after patients had achieved complete response with first-line rituximab-chemotherapy Conditions: Diffuse Large B-cell Lymphoma Intervention / Treatment: DRUG: Everolimus, DRUG: Everolimus Placebo Location: Hungary, Canada, Turkey, Egypt, United States, Greece, Colombia, Austria, Czechia, France, Poland, Israel, Venezuela, Thailand, Italy, Peru, Singapore, Russian Federation, Spain, Brazil, Lebanon, Saudi Arabia, China, Mexico, Norway, Germany, Japan, Korea, Republic of, New Zealand, Switzerland, Australia, Slovakia, Hong Kong, Argentina Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Patients with previous histologically confirmed Stage III-IV (or Stage II bulky disease, defined as any tumor mass more than 10 cm in longest diameter), at time of original diagnosis, diffuse large B cell lymphoma (pathology report based on original tumor tissue/lymph node is acceptable for meeting inclusion criteria, but tumor tissue (slides/block) must be available to be sent for central pathology to confirm diagnosis). * Patients defined as poor risk with IPI of 3, 4, or 5 at time of original diagnosis. * Patients age >= 18 years old. * Patients must have achieved complete remission (CR) based on the revised IWRC (Cheson et al 2007) following first line R-chemotherapy treatment. Radiation therapy (RT) during or after R-chemotherapy is acceptable provided: 1) it ends 4 weeks prior to start of study drug and, 2) in case of consolidation RT targeted at initial bulky tumor mass, administered after R-chemotherapy, patient is already in CR before initiating RT. Complete remission from R-chemotherapy must be confirmed by clinical and radiologic evaluation along with bone marrow confirmation (if bone marrow was involved by lymphoma before the R-chemotherapy treatment). Local pathology report on the bone marrow biopsy is acceptable. If bone marrow was not involved by lymphoma before R-chemotherapy treatment, then bone marrow confirmation after R-chemotherapy is not required. * Patients who received a minimum 5 cycles of R-chemotherapy treatment and maximum 8 cycles of R-chemotherapy treatment. Any variation of CHOP (R-CHOP-14, R-CHOP-21) is acceptable. Liposomal doxorubicin, epirubicin, or pirarubicin (also known as therarubicin) is acceptable. R-EPOCH is acceptable. * Patients' last treatment with R-chemotherapy must be 6 to 14 weeks prior to start of study drug. * Patients with ECOG performance status (PS) 0, 1, or 2. * Patients willing to provide a portion of his/her tumor tissue from original diagnosis or lymph node to confirm diagnosis. * The following laboratory values obtained <= 21 days prior to start of study drug: * Absolute neutrophil count >= 1000/mm3 (or 1.0 GI/L, SI units) * Platelet count >= 100,000/mm3 (or 100 GI/L, SI units) * Hemoglobin >= 9 g/dL (can be achieved by transfusion) * Total bilirubin <= 2 x ULN (if >2 x ULN direct bilirubin is required and should be <=1.5 x ULN) * AST <= 3 x ULN * Serum creatinine <= 2 x ULN * Women of childbearing potential must have had a negative serum pregnancy test 14 days prior to the start of study drug plus a negative local urine pregnancy test on Day 1, Cycle 1 prior to treatment and must be willing to use adequate methods of contraception during the study and for 8 weeks after study drug administration. * Patients who give a written informed consent obtained according to local guidelines. * Patients capable of swallowing intact study medication tablets and following directions regarding taking study drug, or have a daily caregiver who will be responsible for administering study drug. Exclusion Criteria: * Patients with evidence of disease according to the revised IWRC (Cheson et al 2007) after completion of the first-line R-chemotherapy treatment, prior to study entry. * Patients receiving ongoing radiation therapy or who received radiation therapy to the residual tumor masses < 4 weeks from start of study drug. * Patients who have previously received systemic mTOR inhibitor (sirolimus, temsirolimus, everolimus, etc). * Patients with evidence of current central nervous system (CNS) involvement with lymphoma. Patients who have only had prophylactic intrathecal chemotherapy against CNS disease are eligible. * Patients with transformed follicular lymphoma. * Patients who received ibritumomab tiuxetan (Zevalin®), in order to avoid potential delayed kidney toxicities. * Patients who had myelosuppressive chemotherapy or biologic therapy < 3 weeks from start of study drug. * Patients receiving chronic systemic immunosuppressive agents. Inhaled and topical steroids are acceptable. Patients may be receiving stable (not increased within the last month) chronic doses of corticosteroids with a maximum dose of 20 mg of prednisone or <=5 mg of dexamethasone per day, if they are being given for disorders other than lymphoma such as rheumatoid arthritis, polymyalgia rheumatica, adrenal insufficiency or asthma. * Patients with active, bleeding diathesis. * Patients with a known history of HIV seropositivity. * Patients with known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to any of the excipients. * Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: * unstable angina pectoris, symptomatic congestive heart failure (NYHA II, III, IV), myocardial infarction <= 6 months prior to first study drug, serious uncontrolled cardiac arrhythmia, cerebrovascular accidents <= 6 months before study drug start * severely impaired lung function as defined as spirometry and DLCO that is <= 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air * poorly controlled diabetes as defined by fasting serum glucose >2.0 x ULN * any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study * nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by this study drug, such as severe hypertension that is not controlled with medical management and thyroid abnormalities whose thyroid function cannot be maintained in the normal range by medication * liver disease such as cirrhosis or decompensated liver disease. * Patients who have a history of another primary malignancy <= 3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of uterine cervix. * 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. * Patients who are using other investigational agents or who had received investigational drugs <= 4 weeks prior to study drug start. * Patients unwilling to or unable to comply with the protocol.

Study Objectives A study team with extensive experience in immunization delivery research will evaluate the effectiveness of vaccination reminder/recall systems for adolescent patients in five types of clinical settings including: urban pediatric, urban family medicine and rural family medicine practices, public pediatric clinics, and school-based health centers. Randomized controlled trials of reminder/recall for adolescents will be conducted at each type of site, with randomization at the level of the patient. Conditions: Human Papilloma Virus (HPV), Tetanus-diphtheria-acellular Pertussis (Tdap), Meningococcal Infection, Varicella Intervention / Treatment: OTHER: Reminder/recall notices for vaccines Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * children ages 11-18 * seen in practice in last 2 years * not up-to-date on any or all shots (Tdap, HPV, meningococcal) * parents agree to participate in Colorado Immunization and Information System registry Exclusion Criteria: * up-to-date on all vaccines * under age 11 over age 18 * patients who have moved or gone elsewhere at each practice setting

Study Objectives A First-in-human, dose-escalation, dose-expansion phase I clinical study of JS004 in subjects with recurrent/refractory malignant lymphoma in China, to evaluate the safety, tolerbility, PK, immunogenicity,antitumor activity and biomarkers of JS004, to define MTD and RP2D of JS004. A cycle is 21 days(3 weeks) which includes JS004 being administered IV Q3W and JS004 combine with JS001 being administered IV Q3W. All patients will be treated until disease progression per Lugano response critieria 2014 for Lymphoma or intolerable toxicity per CTCAE 5.0, withdrawal of consent, or end of the study, whichever occurs first. Disease progression must be confirmed at least 4 weeks but no longer than 8 weeks after initial documentation of progression. Conditions: Recurrent/Refractory Malignant Lymphoma Intervention / Treatment: BIOLOGICAL: JS004 , Recombinant humanized IgG4k monoclonal antibody specific to BTLA for injection Intravenous infusion, BIOLOGICAL: Drug：JS001, Intravenous infusion Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: *Able to understand and sign informed consent voluntarily *18-70 years old *Pathologically confirmed malignant lymphoma *ECOG PS: 0-1 *Expected survival >=12 weeks *At least one measurable lesion per Lugano response critieria 2014 for Lymphoma *Adequate organ and marrow function, as defined below: ANC>=1.5×109/L; PLT>=100×109/L and >=75×109/L for subjects with bone marrow involvement; Hb>=90 g/L; TBIL<=1.5 ULN, <=2 ULN in those with hep109atic metastasis, except subjects with documented Gilbert's syndrome who must have a baseline conjugated bilirubin <=3.0 mg/dL; AST and ALT<=2.5 ULN, <=5 ULN in those with hepatic metastasis; Cr<=1.5 UL, or creatinine clearance>=50mL/min for subject; INR <=2 ULN and aPTT<=1.5×ULN for those with no prior anticoagulant therapy. *According to Fridericia's principle, QTC results need to match : Male<=450 ms，Female<=470 ms *Females of childbearing potential need to use effective contraception Exclusion Criteria: * Patients with known allergy to macromolecular protein preparations or JS004 components * Prior exposure to anti-BTLA or anti-HVEM antibodies * Enrolled in other clinical studies within 4 weeks prior to the first dose of study treatment * Major surgery within 4 weeks prior to the first dose of study treatmentor still recovering from prior surgery * Patients who discontinued previous immunotherapy due to immune-related adverse reactions * Immunosuppressive agents have been used within 4 weeks prior to the first dose of study treatment * Prior allogeneic bone marrow transplantation or solid organ transplantation * Live attenuated vaccine be administered 30 days before the first dose of study treatment * Two or more malignancies developed within 5 years prior to first dose of study treatment * The patients have symptomatic, untreated, or requiring ongoing treatment central nervous system (CNS) metastases * Unresolved toxicities from prior anticancer therapy, defined as having not resolved to baseline or to NCI-CTCAE v5.0 Grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria with the exception of alopecia.Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by TAB004 may be included (e.g., hearing loss) after consultation with the medical monitor. * Autoimmune disease within the previous 2 years * A history of rapid allergic reaction, eczema, or asthma beyond the control of topical corticosteroids * A history of primary immunodeficiency * Concomitant disease that is not under control, including but not limited to: persistent or active infection, unexplained fever > 38.5°C, or heart disease, active peptic ulcer disease or gastritis * A history of active inflammatory bowel disease * HIV(+) * Patients with evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection * Pregnant or lactating woman * Patients with vitiligo, alopecia, and hormonal replacement therapy have controlled endocrine defects * Any other medical factors that may affect subjects' rights, safety, compliance, ability to sign informed consent, and interpretation of study results. * Have a history of psychotropic drug abuse and unable to withdraw or have mental disorders.

Study Objectives The purpose of this study is to compare how subjects feel after receiving injections of two different types of GnRH six months apart. One injection is given under the skin of the abdomen, and the other one into the muscle of the buttock or thigh. Conditions: Prostate Cancer Intervention / Treatment: DRUG: Triptorelin pamoate, DRUG: Leuprolide acetate Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * Male patients with a diagnosis of advanced prostate cancer for whom treatment with triptorelin pamoate or leuprolide acetate is indicated; * At least 18 years of age; * Life expectancy of at least 1 year; * Capable of completing the study questionnaires without assistance. Exclusion Criteria: * Patients for whom treatment with triptorelin pamoate or leuprolide acetate is contraindicated; * Known hypersensitivity to triptorelin, leuprolide or any other GnRH or luteinizing hormone releasing hormone (LHRH) agonists, or GnRH or LHRH; * Clinically significant systemic disease or condition that would, in the investigator's opinion, lead to undue risk following administration of either triptorelin or leuprolide; * History of alcohol/drug abuse within the past year; * History of significant medical problems that may confound the outcome of this study; * Requires concomitant medications that may affect study assessments (e.g., topical medications used for pretreatment of injection site pain); * Participated in another investigational drug study within 30 days * Judged by the investigator to be unsuitable for enrollment in this study for any reason

Study Objectives This is a pilot study to investigate the evaluate to use of a drug/radiopharmaceutical called Gallium-68 PSMA-11 (68Ga-PSMA-11) for use in PET/MRI evaluation of hepatocellular carcinoma Conditions: Hepatocellular Carcinoma Intervention / Treatment: DRUG: 68Ga-PSMA-11 PET/MRI Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: EARLY_PHASE1 Primary Purpose: DIAGNOSTIC Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients at risk for HCC with either an imaging diagnosis of HCC by ceCT or ceMRI (LI-RADS 5) confirmed by a board-certified abdominal radiologist or biopsy-proven HCC confirmed by a hepatobiliary pathologist * No prior treatment for HCC * Subjects who are expected to undergo surgical resection of the hepatic lesion(s) and/or liver transplant * Male or female with age greater than 18 years, with the capacity to give informed consent and willingness to provide a written consent. Exclusion Criteria: * Subjects requiring emergent surgery for a ruptured/bleeding HCC * Bilirubin > 3.0 mg/dL, which is a contraindication for Gadoxetate, the MRI contrast agent * Pregnant and/or breast-feeding subjects. A negative pregnancy test within 48 hours of the PET scan. * Subjects with higher than the weight/size limitations of PET/MRI scanner. * Subjects with contraindication to MRI including: Subjects who have a heart pacemaker, subjects who have a metallic foreign body (metal sliver) in their eye, or who have an aneurysm clip in their brain, subjects who have implanted devices with magnets, subjects who have other implanted electronic devices, subjects who have deep brain stimulator, subjects who have vagal nerve stimulator, subjects with cochlear (ear) or auditory implants * Subjects with history of allergic response to radiocontrast media * Subjects with known history of claustrophobia.

Study Objectives Triple-negative breast cancer (TNBC) is a special type of breast cancer, endocrine therapy and targeted therapy are completely ineffective, chemotherapy is currently the only effective treatment. How to improve postoperative pathologic complete response（pCR）of neoadjuvant chemotherapy is critical problem to prolong event-free survival (EFS) and overall survival (OS) of TNBC patients. Apatinib is a new oral small molecule tyrosine protease inhibitor, it is effective in inhibiting angiogenesis with a very low concentration. So the standard neoadjuvant chemotherapy regimen of docetaxel and carboplatin combined with apatinib may improve the postoperative pCR and survival outcomes of TNBC patients. Safety and tolerability assessed by number of grade 3 and 4 toxicities and hospitalizations. Conditions: Triple-Negative Breast Cancer Intervention / Treatment: DRUG: Apatinib Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically or pathologically confirmed noninflammatory Triple-Negative invasive breast carcinoma (TNBC). The diagnosis of TNBC was defined below: the estrogen receptor and progesterone receptor negativity rates were less than 10%, and the human epidermal growth factor receptor type 2 (HER2) staining was 0 or 1+, and fluorescence in situ hybridization (FISH) detected no HER2 gene amplification * Clinical stage IIA-IIIB * Patients must have measurable disease as defined by palpable lesion with caliper and/or a positive mammogram or ultrasound. Bilateral mammogram and clip placement is required for study entry. Baseline measurements of the indicator lesions must be recorded on the Patient Registration Form. To be valid for baseline, the measurements must have been made within the 14 days if palpable. If not palpable, a mammogram or MRI must be done within 14 days. If palpable, a mammogram or MRI must be done within 2 months prior to study entry. If clinically indicated, x-rays and scans must be done within 28 days of study entry. * Eastern Cooperative Oncology Group(ECOG) performance status 0 to 1 within 14 days of study entry * Signed informed consent * Adequate organ function within 2 weeks of study entry: Absolute bone marrow function (hemoglobin concentration of >=8.0 g/dL, white blood cell count of >=3000 cells per μL, absolute neutrophil count of >=1500 cells per μL, platelet count of >=70000 cells per μL), adequate renal function (creatinine was the upper limit of normal or lower), and adequate liver function (total bilirubin was the upper limit of normal or lower, and aspartate aminotransferase or alanine aminotransferase was twice the upper limit of normal or lower) * Patients must be aged 18-70 years * Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment * Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Exclusion Criteria: * Metastatic disease * Prior chemotherapy, hormonal therapy, biologic therapy, investigational agent, targeted therapy or radiation therapy for current breast cancer. Patients with history of breast cancer greater than 5 years from initial diagnosis are eligible for the study. Patients may not have received anthracycline-based chemotherapy in the past. Patients with history of ductal carcinoma in situ(DCIS) are eligible if there were treated with surgery alone * History of previous or current malignancy at other sites with the exception of adequately treated carcinoma in-situ of the cervix or basal or squamous cell carcinoma of the skin. Patients with a history of other malignancies, who remain disease free for greater than five years are eligible * Uncontrolled blood pressure, previous exposure to apatinib, known allergies to any of the excipients, and a history of unstable angina, myocardial infarction, or class III/IV congestive heart failure (defined by the New York Heart Association) within the past 6 months before day 1 of the trial

Study Objectives To provide study drug to patients that benefit from treatment judged by the investigator - to obtain additional long-term safety and efficacy data of this combination regimen in GIST Conditions: Gastrointestinal Stromal Tumors Intervention / Treatment: DRUG: Nilotinib, Imatinib Location: United States, Italy, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion criteria: * Documented Complete Response, Partial Response, or Stable Disease at the time of entry to extension study and/or possible benefit from continuing treatment in the view of the investigator. * Normal organ and marrow function as defined in core protocol (CAMN107A2103). * Extension protocol written informed consent. Exclusion criteria: * Inability to swallow the medication. * Any unresolved adverse events related to participation in the core protocol (CAMN107A2103). * A history of noncompliance to medical regimens or inability or unwillingness to return for all scheduled visits. Other protocol defined inclusion/exclusion criteria may apply.

Study Objectives Currently, there are few effective treatments for the following aggressive brain tumors: glioblastoma multiforme, anaplastic astrocytoma, gliomatosis cerebri, gliosarcoma, or brainstem glioma. Surgery and radiation can generally slow down these aggressive brain tumors, but in the majority of patients, these tumors will start growing again in 6-12 months. Adding chemotherapy drugs to surgery and radiation does not clearly improve the cure rate of children with malignant gliomas. The investigators are conducting this study to see if the combination of valproic acid and bevacizumab (also known as AvastinTM) with surgery and radiation will shrink these brain tumors more effectively and improve the chance of cure. Conditions: Glial Cell Tumors, Malignant Gliomas, Glioblastoma Multiforme, Anaplastic Astrocytoma, Gliomatosis Cerebri, Gliosarcoma, Brainstem Glioma, Diffuse Intrinsic Pontine Glioma Intervention / Treatment: DRUG: Valproic acid, DRUG: Bevacizumab, RADIATION: Radiation 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: * Patient must be greater than or equal to 3 years and less than or equal to 21 years of age at the time of study enrollment. * Patients must have histologic verifications of a glioblastoma multiforme, anaplastic astrocytoma, gliomatosis cerebri (WHO grade III or IV glioma with diffuse parenchymal and/or leptomeningeal involvement), or gliosarcoma at the time of study enrollment. Patients with newly diagnosed intrinsic brainstem gliomas, defined as tumors with a pontine epicenter and diffuse rather than focal involvement of th pons, with or without extension to adjacent medulla or midbrain, are eligible without histologic confirmation. Patients with brainstem tumors that do not meet these criteria or not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to be a grade III or IV glioma (anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma). * Patients must have Karnofsky Performance Score (for patients greater than 16 years of age) or Lansky Performance Score (for patients less than or equal to 16 years of age) greater than or equal to 50% assessed within two weeks of study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. * Patients must not have received any prior chemotherapy, radiation therapy, biologic therapy, or bone marrow transplant. Surgery and dexamethasone are permitted prior to study entry. In patients who require anti-convulsant prior to study entry, it is permissible to start VPA, but trough VPA concentration must be repeated within 48 hours of study entry. * Patients must have adequate bone marrow function defined as: - Hgb greater than or equal to 8 gm/dL (transfusion independent) - Platelet count greater than or equal to 100,000/mm3 (transfusion independent) - Absolute neutrophil count (ANC) greater than or equal to 1,000/ mm3 * Patients must have adequate liver function defined as: * Bilirubin (sum of conjugated + unconjugated) less than or equal to 1.5 times institutional upper limit of normal (ULN) for age. * SGPT (ALT) less than or equal to 2.5 times institutional ULN for age. * Serum albumin greater than or equal to 2 g/dL. * Patients must have adequate renal function defined as: * Urine protein (albumin)/creatinine ratio of less than 1.0 * Creatinine clearance or radioisotope GFR greater than or equal to 70 ml/min/1.73m2 OR * A serum creatinine based on age and gender as follows: * 2 to less than 6 years of age: 0.8 mg/dL for male and female * 6 to less than 10 year of age: 1.0 mg/dL for male and female * 10 to less than 13 years of age: 1.2 mg/dL for male and female * 13 to less than 16 years of age: 1.5 mg/dL for males and 1.4 for females * Greater than or equal to 16 years of age: 1.7 mg/dL for males and 1.4 mg/dL for females Note: The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC. * Amylase and lipase less than or equal to 2 times institutional ULN for age. * Patients must not have a prolonged PT or PTT (greater than 1.2 times the institutional upper limit of normal), and the INR must be less than 1.5. * MRI ECHO gradient sequences are required to evaluate for the presence or absence of CNS hemorrhage. Patients with intra-tumoral and/or CNS hemorrhage are eligible for study entry if they fulfill the following guidelines: * Patients with an asymptomatic intra-tumoral/intracranial hemorrhage measuring less than 1 cm in the widest dimension on MRI at the time of diagnosis, after surgery, and/or any time prior to study enrollment, are eligible; hemorrhage must not have progressed on MRI prior to initiation of protocol therapy; patients mut not have developed progressive symptoms thought to be related to the intra-tumoral/intracranial hemorrhage prior to initiation of protocol therapy. * Patients with a greater than 1 asymptomatic intra-tumoral/intracranial hemorrhage but all measuring less than 1 cm in the widest dimension on MRI are eligible if they fulfill the guidelines described above. * Patients with asymptomatic post-operative hemorrhage in and/or around the surgical cavity are eligible for study entry if they otherwise fulfill the guidelines described above. * Patients with an intra-tumoral hemorrhage greater than 1 cm at diagnosis but who demonstrate minimal post-operative hemorrhage as described above after tumor resection are eligible for study. * Patients must begin radiation therapy within 30 days of surgery or radiographic diagnosis, whichever is the later date. * All patients and/or their legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines. Exclusion Criteria: * Females of reproductive potential must not be pregnant or lactating. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. * Patients with active or history of cardiac (CHF, myocardial infarction, myocarditis) disease are excluded from this trial. * Patients receiving any of the following medications are not eligible for study entry: a. Anti-cancer therapy or investigational agents b.Anti-coagulants (except for heparin to maintain the patency of central venous catheters). c.Growth factors for white blood cell, red blood cell or platelet support d.Aspirin (> 81 mg/day) e.Non-steroidal anti-inflammatory drugs f.Clopidogrel (Plavix), Dypiramidole (Persantine), or any other drug that inhibits platelet function g. Anti-convulsants: patients on any anti-convulsant with the exception of VPA are eligible for study entry. It is strongly recommended that a neurology consult be obtained to enable discontinuation of all anti-convulsant other than VPA, whenever possible. * Patients who have an uncontrolled infection are not eligible. * Patients with inadequately controlled systemic hypertension (SBP and/or DBP greater than 95th percentile for age and height) * Patients with a prior history of hypertensive crisis and/or hypertensive encephalopathy If a BP measurement prior to registration is greater than 95th percentile for age and height, it must be rechecked and documented to be less than 95th percentile for age and height prior to registration. If a patient falls between the height or weight percentiles, site should average the value as appropriate. For patients greater than or equal to 18 years, use adult normal ranges for blood pressure. Patients with hypertension are eligible if their blood pressures become less than 95th percentile after anti hypertensive medications. * Prior Ischemic Events: Patients with a history of stroke, myocardial infarction, or unstable angina within 6 months prior to registration are not eligible. * Vascular Disease: Patients with significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to registration will not be eligible. * Patients with a history of hemoptysis, bleeding diathesis, known platelet disorder, or coagulopathy are not eligible. * Patients with a history of abdominal fistula or GI perforation within 6 months prior to registration are not eligible. * Patients with a known or suspected urea cycle or other metabolic disorder are not eligible. * Patients with abnormality of the tibial metaphyseal plate on plain X-ray prior to study entry are not eligible. * Patients with a history of a serious non-healing wound, ulcer, or bone fracture are not eligible. * Patients with any clinically significant systemic illness, including serious infection, pulmonary, hepatic, or other organ impairment, that would compromise tolerance and/or timely completion of protocol therapy. * Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements and/or follow-up studies of this trial. * Patients with a known hypersensitivity to any component of bevacizumab are not eligible for this trial.

Study Objectives This is an open-label, single arm study to explore whether 18F-ALF-NOTA-PRGD2 PET/CT scan can predict the efficacy and adverse events of apatinib in patients with malignancies. Integrin αvβ3 has been shown to play an important role in angiogenesis and up-regulated obviously in various types of tumor cells and activated endothelial cells. The arginine-glycine-aspartic acid (RGD) tripeptide sequence can bind to integrin αvβ3 with high affinity and specificity. The 18F-ALF-NOTA-PRGD2 will highly combine with αvβ3, and thus will monitor the antiangiogenic status.In the current study, investigators propose to evaluate the feasibility of 18F-RGD PET/CT in monitoring efficacy and adverse events of apatinib in malignancies. Conditions: Malignancies, Stomach Cancer, Non-small Cell Lung Cancer, Esophageal Cancer, Breast Cancer, Ovary Cancer, Cervical Cancer Intervention / Treatment: DRUG: Apatinib Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Clinical diagnosis of malignancies * Scheduled for second- or third-line apatinib therapy * Karnofsky performance status (KPS) >=70 * Measurable primary tumors according to Response Evaluation Criteria in Solid Tumors (RECIST) Exclusion Criteria: * Active infection, myocardial infarction within 6 months, symptoms of heart disease, including unstable angina, congestive heart failure or uncontrolled arrhythmias, immunosuppressive therapy * The claustrophobic patients and patients with implanted metal objects * The pregnancy * Inability to complete the required examinations

Study Objectives This phase II trial is studying how well giving O6-benzylguanine together with temozolomide works in treating young patients with recurrent or progressive gliomas or brain stem tumors. Drugs used in chemotherapy, such as O6-benzylguanine and temozolomide , work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. O6-benzylguanine may help temozolomide work better by making tumor cells more sensitive to the drug. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Conditions: Brain and Central Nervous System Tumors Intervention / Treatment: DRUG: O6-benzylguanine, DRUG: temozolomide 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 * Tumor: Participants must have a high-grade glioma (including e.g. histologically confirmed anaplastic astrocytoma, glioblastoma multiforme, anaplastic oligodendroglioma, anaplastic ganglioma, gliosarcoma) or a brainstem tumor (histologic confirmation waived) with documentation of disease recurrence or progression after treatment with standard therapy. Participants must have bi-dimensionally measurable disease, defined as at least 1 lesion that can be measured in >= 2 dimensions * Age: 21 years of age or less * Performance status: Karnofsky 60-100% (for patients > 16 years of age) or Lansky 60-100% (for patients <= 16 years of age) * Life expectancy: Not specified * Hematopoietic: Must have adequate bone marrow function defined as absolute neutrophil count > 1,500/mm^3, platelet count > 100,000/mm^3 (unsupported), hemoglobin > 8 g/dL (may be supported), and absolute lymphocyte count >= 500/mm^3 * Hepatic: Must have SGOT and SGPT <= 2.5 times upper limit of normal (ULN), bilirubin <= 1.5 times ULN, and no overt hepatic disease * Renal: Participants must have creatinine clearance >= 60 mL/min or creatinine based on age as follows: no greater than 0.8 mg/dL (for patients <= 5 years of age), no greater than 1.0 mg/dL (for patients 6 to 10 years of age), no greater than 1.2 mg/dL (for patients 11 to 15 years of age), or no greater than 1.5 mg/dL (for patients > 15 years of age). There must be no overt renal disease * Cardiovascular: Must have no overt cardiac disease * Pulmonary: Must have no overt pulmonary disease * Other: Female participants of childbearing potential must have a negative pregnancy test prior to study registration, and must avoid breast-feeding. Female and male participants of childbearing or child-fathering potential must use effective contraception * Bone Marrow Transplant: Must be at least 6 months since prior allogeneic bone marrow transplantation and at least 3 months since prior autologous bone marrow or stem cell transplantation * Growth Factors: Must be at least 2 weeks since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or erythropoietin) * Prior Chemotherapy: Must have received last dose of myelosuppressive anticancer chemotherapy >= 3 weeks prior to study registration and >= 6 weeks for nitrosoureas. Must have received last dose of nonmyelosuppressive investigational agents or anticancer drugs >= 7 days prior to study registration. Participants who have received prior temozolomide are eligible * Concurrent Endocrine Therapy: Concurrent corticosteroid therapy is allowed * Prior Radiotherapy: Must have received last fraction of craniospinal irradiation and local irradiation to the primary tumor >= 12 weeks prior to study registration * Prior Therapy-Other: Must have recovered from all prior therapy EXCLUSION CRITERIA * Must not have history of severe toxicity (>= grade 3) associated with temozolomide * Must not be receiving other concurrent anticancer or investigational therapy * Must not have history of hypersensitivity to dacarbazine, temozolomide, or polyethylene glycol (PEG) * Must not have uncontrolled significant systemic illness including infection, or overt renal, hepatic, cardiac, or pulmonary disease * Must not be HIV positive

Study Objectives Multi-agent chemotherapy has value for patients with advanced pancreatic-biliary cancers leading to responses in a substantial minority and increasing survival. The use of the FOLFIRINOX regimen is limited by its' intensity and toxicity. Previous protocol and clinical experience within the University of Michigan Pancreatic Program leads to an expectation of tolerance and efficacy of the proposed regimen. Advantages of the proposed regimen relative to FOLFIRINOX include: 1. Substitution of gemcitabine for irinotecan. Single agent activity of gemcitabine is at least as good as irinotecan (probably better, especially when delivered by FDR \[fixed-dose rate\] infusion) and gemcitabine is much better tolerated with less diarrhea, nausea/emesis, myelosuppression and alopecia. 2. Deletion of leucovorin infusion and 5FU bolus injection will lessen myelosuppression, mucositis and diarrhea. 3. Substitution of cisplatin for oxaliplatin will reduce cost of therapy and avoid cold aggravated dysesthesia. Presuming evidence of efficacy and confirmation of tolerance with the proposed regimen, the investigators believe this treatment may be more widely applicable to pancreatic-biliary cancer patients, including those with advanced disease as well as being considered for use in locally advanced and neo- and adjuvant settings. Conditions: Pancreatic Cancer, Biliary Cancer Intervention / Treatment: DRUG: Gemcitabine, DRUG: 5-FU, DRUG: Cisplatin 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 histologic or cytologic diagnosis of pancreatic adenocarcinoma or biliary tract cancer (intrahepatic or extrahepatic cholangiocarcinoma or gallbladder carcinoma). * Patients must have clinical/radiologic evidence of metastatic disease. * Previous systemic therapy for metastatic disease limited to one cytotoxic chemotherapy regimen not containing cisplatin. Previous therapy for metastatic disease might have included gemcitabine or infusional 5-FU but not both agents. * ECOG (Eastern Cooperative Oncology Group) performance status < 1 (A measure of quality of life where 0 represents asymptomatic and 5 represents death). * Patients must have adequate bone marrow (absolute neutrophil count >1,500/mm3, platelet count >100,000/mm3) and renal function (serum creatinine < 1.25 x ULN). * Patients must have at least one measurable lesion per RECIST criteria. * Patients must be free of serious concomitant medical disorders incompatible with study participation including active infection requiring systemic therapy. * Previous malignancies are permitted provided that they have been treated with curative intent and patient is without evidence of active systemic disease. * Patients must be informed of the investigational nature of this study and provide written informed consent prior to receiving protocol treatment. Exclusion Criteria: * Patients with pre-existing peripheral neuropathy > grade 2 are ineligible. * Previous systemic therapy for metastatic disease limited to one cytotoxic chemotherapy regimen not containing cisplatin. * Previous therapy for metastatic disease might have included gemcitabine or infusional 5-FU but not both agents. * Serious concomitant medical disorders incompatible with study participation including active infection requiring systemic therapy.

Study Objectives A 2-part study to examine safety, tolerability and pharmacokinetics (part 1), and anti-tumour effects (part 2), of CDP791 combined with carboplatin and paclitaxel. Conditions: Carcinoma, Non-Squamous Non-Small-Cell Lung Cancer Intervention / Treatment: DRUG: Carboplatin, DRUG: Paclitaxel, DRUG: CDP791 10mg/kg, DRUG: CDP791 20mg/kg Location: Hungary, Russian Federation, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: Inclusion Criteria: * Male and female subjects with Stage IIIb (with malignant pleural effusion or if no pleural effusion is present subjects who are not candidates for combined modality therapy), Stage IV, or recurrent non-squamous, non-small-cell lung carcinoma. * The subject must be aged 18 years or above. * The subject must have ECOG performance status of 0 or 1 and a life expectancy of at least three months. * Subjects will have measurable disease. * The subject must be able to understand the information provided to them and to give written informed consent. * Female subjects must be either postmenopausal, surgically sterilized, or using a method of contraception judged reliable by the Investigator. * Male subjects must be using a method of contraception judged reliable by the Investigator. Exclusion Criteria: * Subjects with squamous cell lung carcinoma. * Subjects with lung lesions located centrally in the chest that involve major blood vessels. * Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix. Subjects with previous malignancies are eligible provided that they have been disease free for five years or more. * Presence of additional major chronic disease such as hepatic or renal dysfunction, cardiac dysfunction, peripheral vascular disease, evidence of a myocardial infarction within six months of Screening visit, tuberculosis or epilepsy. * Subjects known to be infected with hepatitis B or C virus or HIV 1 or 2. * Any evidence of serious active infection (ie requiring an iv antibiotic or antiviral agent). Exclusion Criteria:

Study Objectives This is a phase II, open label, single center study to evaluate the efficacy of abiraterone acetate (CB7630) administered to patients with castrate resistant prostate cancer who have experienced disease progression on ketoconazole. It is hypothesized that abiraterone will be active in patients who have experienced disease progression on ketoconazole Conditions: Prostate Cancer Intervention / Treatment: DRUG: Abiraterone acetate 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 confirmed adenocarcinoma of the prostate * Prior therapy with ketoconazole for castration resistant prostate cancer. Patients should demonstrate evidence of progression (see below definitions) on ketoconazole or evidence of grades 3/4 toxicities on ketoconazole. 1. Ketoconazole must have been administered for >28 days 2. At least 27 days must elapse since last ketoconazole dose and first dose of abiraterone acetate * No prior therapy with chemotherapy for metastatic prostate cancer * Metastatic disease based on a positive bone scan or objective imaging on CT scan * Ongoing gonadal androgen deprivation therapy with LHRH analogues or orchiectomy. Patients, who have not had an orchiectomy, must be maintained on effective LHRH analogue therapy for the duration of the trial * Testosterone < 50 ng/dL * Progressive disease after androgen deprivation: PSA evidence for progressive prostate cancer consists of a PSA level of at least 2 ng/ml which has risen on at least 2 successive occasions, at least 2 weeks apart * Patients who are receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression following discontinuation of antiandrogen * ECOG Performance Status 0-1 * Age >18 years and able to comply with protocol requirements * Serum Creatinine <=1.5 x ULN * Serum potassium >3.5mmol/L * Bilirubin <=1.5x ULN * AST and ALT <=2.5 x ULN * Life expectancy of >12 weeks Exclusion Criteria: * Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace), finasteride (Proscar), dutasteride (Avodart) any herbal product known to decrease PSA levels (e.g., Saw Palmetto and PC-SPES), or any systemic corticosteroid within 4 weeks prior to first dose of study drug * Therapy with supplements or complementary medicines/botanicals within 4 weeks of first dose of study drug, except for any combination of the following; conventional multivitamin supplements, Selenium, Lycopene and Soy supplements * Prior radiation therapy completed < 4 weeks prior to enrollment * Prior chemotherapy for castration resistant prostate cancer. Patients who have received chemotherapy for early stage prostate cancer (e.g. as part of a neoadjuvant or adjuvant trial) or for other malignancies are eligible provided that >1 year has passed since the administration of the last chemotherapy dose. * Hemoglobin <=9.0 g/dL * Any "currently active" second malignancy, other than non-melanoma skin cancer Patients are not considered to have a "currently active" malignancy, if they have completed therapy and are considered by their physician to be at least less than 30% risk of relapse over next 3 months * Blood pressure that is not controlled despite >2 oral agents (SBP >160 and DBP >90 on three or more readings within the screening period) * Serum K+ <3.5 mmoL/L on more than one reading within the screening period * NYHA Class II, NYHA Class III or IV Congestive Heart Failure * Myocardial infarction within the 6 months prior to the first dose of study drug * Serious intercurrent infections or nonmalignant medical illnesses that are uncontrolled * Concurrent therapy with drugs that are metabolized as substrates of CYP1A2, CYP2D6, or CYP2C19 and are considered by the investigators to pose a risk for drug to drug interactions

Study Objectives The study will evaluate if the N-methyl-pyrrolidone (NMP) can be safely administered to humans at doses, which induce measurable immunological and anti-tumour effects in patients with myeloma who are resistant to or intolerant of lenalidomide and bortezomib. Conditions: Multiple Myeloma Intervention / Treatment: DRUG: N-methyl-pyrrolidone Location: Australia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed diagnosis of plasma cell myeloma defined by WHO 2008 criteria * Measurable disease as defined by at least one of: * serum M protein >=5g/L * urine M protein >= 200mg/24hrs * involved serum free light chain >= 100mg/L * measurable (by imaging at the discretion of the investigator) soft tissue plasmacytoma * Relapsed, refractory or intolerant of both bortezomib and lenalidomide Definitions: * refractory at least 4 weeks of therapy administered, with less than a partial response by IMWG criteria * relapsed from previous response (PR or greater) to therapy, with subsequent disease progression as defined as development of bone marrow dysfunction (fall in Hb of 20g/L or platelet count <100 x 109/L) due to increased bone marrow plasmacytosis * OR new lytic bone lesions * OR increase in serum M protein of 5g/L * OR absolute increase of involved serum free light chain of >250mg/L * intolerant: grade 2 or higher toxicity unresponsive to dose adjustment 4. Prior autologous stem cell transplant, unless ineligible for transplant by the discretion of the investigator. 5. age >=18 years 6. ECOG performance status <2 7. The following values within 7 days of commencing NMP (blood transfusions prior to study entry are permitted) * Haemoglobin >80g/L * Absolute neutrophil count >1.0 x 109/L * Platelet count >= 25 x 109/L * Creatinine clearance >30ml/min (by Cockcroft/Gault) * Bilirubin <= 3x upper limit of normal (ULN) * ALT <= 3 x ULN * Left ventricular ejection fraction (LVEF) >=45% (by gated cardiac blood pool scan or echocardiography) 9. Life expectancy > 3 months 10. Able to give written informed consent 11. In the opinion of the investigator, willing and able to comply with required study procedures 12. Able to take oral medications (no malabsorptive condition) Exclusion Criteria: * Pregnant or breastfeeding female patients * Female of child bearing potential unwilling or unable to use two methods of contraception * Received chemotherapy, immunotherapy or biological therapy within two weeks of enrolment. Prednisolone up to 20mg per day permitted for non-myeloma indications. * Patients with a history of another malignancy within 2 years of the baseline visit, excluding treated non-melanotic skin cancer and in-situ carcinoma. * Patients with known CNS involvement unless previously treated and well controlled for a period of >=3 months AND which do not require the use of steroids. * Uncontrolled intercurrent illness including, but not limited to: * Active or uncontrolled infection, including active HIV or viral (A, B or C) hepatitis. NOTE: Patients with controlled infection on antibiotic or antifungal therapy are eligible i.e. the patient should be afebrile for at least 72 hours and be haemodynamically stable. * Impaired cardiac function, including any of the following: * Myocardial infarction within previous 3 months prior to starting study * Symptomatic congestive heart failure (New York Heart Association Class III, IV) * Symptomatic coronary artery disease * Cardiac arrhythmia not controlled by medication * Clinically significant resting bradycardia (<50 beats per minute) * Long QT syndrome or a known family history of long QT syndrome or QTc > 450 msec on baseline ECG (using the QTcF formula). If QTcF >450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc * Inability to monitor the QT/QTc interval on ECG * Other clinically significant uncontrolled heart disease (e.g. unstable angina or uncontrolled hypertension) * Impaired hepatic or renal impairment (see inclusion criteria) * Uncontrolled diarrhoea, nausea or vomiting * concomitant exposure to another investigational agent

Study Objectives The purpose of this study is to evaluate pharmacogenomics (PGx) guided drug prescribing for pain and depression in patients with cancer. The investigators aim to understand how PGx testing can be used to improve medication management for pain and depression, and whether PGx-guided prescribing improves these symptoms and quality of life compared to historical controls. Conditions: Cancer, Depression, Pain Intervention / Treatment: OTHER: Preemptive Pharmacogenomic Testing Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SUPPORTIVE_CARE Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria * Written informed consent and HIPAA authorization for release of personal health information. * Completion of ESAS at initial palliative medicine clinic visit, presenting with moderate to high pain (>= 4/10) and/or depression (>= 3/10). * New patients >= 18 years of age who have had an initial visit in the Department of Supportive Oncology's palliative medicine clinic with hematologic malignancy or any stage solid tumor malignancy according to the provider. * Agree to at least one additional palliative medicine clinic visit per protocol. * Able to provide a buccal sample for PGx testing. Exclusion Criteria * Psychiatric illness, social situations, or active/recent (within 30 days) history of illicit substance (e.g. cocaine, heroin) abuse that would limit compliance with study requirements (e.g. clinic visits, medication compliance, etc.) as determined by the Investigator. * Patients who have had prior multiple visits in palliative medicine clinic.

Study Objectives This is a phase I study to find the highest tolerable dose of crizotinib and dasatinib given in combination to patients with diffuse intrinsic pontine glioma (DIPG) and other types of high grade gliomas (HGG). Participants will receive escalating doses until the highest dose is determined. Participants will be enrolled in two strata: stratum A for recurrent/ progressive tumors and stratum B for recently diagnosed patients who have completed standard radiation therapy without progressive disease. Up to 7 dosage levels will be tested. Both drugs are taken orally daily, once per day. Correlative pharmacokinetic and biology studies are planned, as well as advanced methods of magnetic resonance imaging (MRI). Conditions: Diffuse Intrinsic Pontine Glioma, High-grade Glioma Intervention / Treatment: DRUG: Crizotinib, DRUG: Dasatinib 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: ALL RESEARCH PARTICIPANTS * Diagnosis of high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG). If histologic confirmation was obtained, diagnosis must be one of the following: anaplastic astrocytoma (WHO grade 3), anaplastic oligodendroglioma (WHO grade 3), anaplastic oligoastrocytoma (WHO grade 3), anaplastic ganglioglioma (WHO grade 3), pleomorphic xanthoastrocytoma with anaplastic features (WHO grade 3), malignant glioneuronal tumor, glioblastoma, or gliosarcoma (WHO grade 4) * Age > or = 2 years and < or = 21 years * Performance score > or = 50 (Lansky for research participants < or = 16 years and Karnofsky for those > 16 years). * Adequate organ function at the time of enrollment as follows: * Bone marrow: Hemoglobin > or = 8g/dL [may have received packed red blood cell transfusion], absolute neutrophil count (ANC) > or = 1000/mm^3, platelets > or = 100,000/mm^3 [transfusion independent]) * Renal: Normal serum creatinine based on age as shown below or GFR > 70ml/min/1.73m^2: * Age < or = 5 years: 0.8 mg/dL maximum * Age 5 to 10 years: 1.0 mg/dL maximum * Age 10 to 15 years: 1.2 mg/dL maximum * Age > 15 years: 1.5 mg/dL maximum * Hepatic: SGPT and SGOT < 3x the institutional upper limit of normal (ULN), total bilirubin concentration < 1.5x the institutional ULN, albumin > or = 2g/dL * Female research participants > or = 10 years of age or post-menarchal must not be pregnant (confirmed by serum or urine pregnancy test within 1 week of study enrollment) or breastfeeding * Female research participants of childbearing age or males research participants of child fathering potential must agree to use safe contraceptive methods for the duration of the study and for 3 months thereafter Inclusion Criteria: STRATUM A * Diagnosis of recurrent or progressive HGG or DIPG. * Neurological deficits must be stable on a fixed or decreasing dose of dexamethasone for >=7 days before study enrollment. * Recovery to <= grade 1 from all significant toxicities of previous therapies. * Irradiation: Interval from the last dose of local radiation therapy (RT), craniospinal RT, and palliative RT for symptomatic disease > or = 3 months, > or = 6 months, and > or = 2 weeks before study enrollment, respectively * Myelosuppressive chemotherapy: Interval > or = 6 weeks and > or = 4 weeks from last dose of nitrosourea and other chemotherapy drugs before study enrollment, respectively. However, interval must be > or = 1 week from last dose of oral etoposide and other drugs administered at low doses (metronomic regimen) before study enrollment * Small-Molecule Inhibitors: Interval > or = 1 week from last dose before study enrollment. If a previously used agent has a prolonged half-life, the appropriate interval will be determined after consultation with the principal investigator * Monoclonal Antibodies: Interval > or = 3 half-lives before study enrollment. Such cases will need to be discussed with the principal investigator * High-Dose Chemotherapy with Stem-Cell Rescue: Interval > or = 3 months before study enrollment * Cancer Vaccines and Convection-Enhanced Therapies: Interval > or = 1 month before study enrollment * Growth Factors: Interval > or = 1 week and > or = 2 weeks before study enrollment for standard and long-acting growth factors (e.g., pegfilgrastim), respectively Inclusion Criteria: STRATUM B * Completion of local RT with or without concomitant chemotherapy including temozolomide and radiosensitizing agents (e.g., carboplatin, vorinostat) outside the context of a clinical trial. Any agent administered during RT should have a short half-life so that it should already be completely eliminated by the start of this therapy. If other agents were used concurrently with RT, they will need to be discussed with the principal investigator to assess eligibility * Interval > or = 4 weeks and < or = 8 weeks from the completion of radiochemotherapy Exclusion Criteria: ALL RESEARCH PARTICIPANTS * Metastatic disease for stratum B only * Concomitant use of other anticancer (except for corticosteroids) or experimental agents * Use of enzyme-inducing anticonvulsants (EIACs). A minimum interval of 10 days between the last dose of EIAC and start of this therapy will be required for research participants who were previously receiving such medications. * Pregnant or lactating patients * Research participants with other clinically significant medical disorders that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results * Prior therapy with a PDGFR or c-Met inhibitor * Original treatment design: Body surface area >= 1.8m2on dosage levels 3b, 4, and 5 * Modified treatment design: Body surface area < 0.55 m^2 for all dosage levels

Study Objectives Patients will receive Bortezomib, Dexamethasone, and Doxorubicin in 21 day cycles a total of 4 to 8 times (based on response to the treatment). Patients will also receive acetyl-L-carnitine (ALCAR) daily. Conditions: Multiple Myeloma Intervention / Treatment: DRUG: Bort, Dex, and Dox with ALCAR 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 with previously treated multiple myeloma with measurable serum or urine monoclonal protein. Exclusion Criteria: * Patients with previous doxorubicin treatment totaling 220 mg/m2 or more * LVEF less than 45% * Patients with >grade II sensory neuropathy at baseline as assessed by the PI will be excluded * No history of seizures as ALCAR may lower the seizure threshold * Known HIV infection * Current pregnancy.

Study Objectives This trial is to evaluate the potential of colchicine for the palliative management of hepatocellular carcinoma patients with distant metastasis or large vessel invasion using the Department of Health R.O.C. approved doses and methods of administration. Conditions: Hepatocellular Carcinoma, Metastasis, Invasion Intervention / Treatment: DRUG: Colchicine Location: Taiwan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * . Patient has at least one of the following criteria: (1) positive for hepatocellular carcinoma evidenced by cytology or pathology, (2) serum alpha-fetoprotein level > 400 ng/mL and has evidence of hepatocellular carcinoma provided by contrast-enhanced computed tomography or magnetic resonance imaging. * . Contrast-enhanced computed tomography or magnetic resonance imaging has evidence of distant metastasis or large vessel invasion caused by hepatocellular carcinoma. * . Patient has Child A hepatic reserved function Exclusion Criteria: * . There are life-threatening hemorrhage including gastrointestinal hemorrhage and hemorrhage from other vital organs such as lungs or brain. * . There are life-threatening bacterial, fungal or viral infection (not included hepatitis B and C virus). * . Patient has serum creatinine level > 1.5 mg/dL. * . Patient must receive long-term medication of statin or fibrates drugs and these medications can not be changed. * . Patient has white blood cell count < 1500/µL, platelet count < 30000/µL or hemoglobin < 9.0 gm/dL after medication. * . Pregnant woman or plan to be a pregnant woman * . allergy to colchicine or has history of severe side effects caused by colchicine * . Patient has received systemic chemotherapy within 2 months before enrollment or plans to receive systemic chemotherapy in the future. * . Patient is under or plans to receive Nexavar or other clinical trial testing drug. * . Patient has severe malfunction of vital organs and can not participate in this study justified by the doctor in this research team. * . Patient is under or plans to receive Chinese traditional medicine or herb drugs.

Study Objectives This is a non-randomised study assessing the technique of using indocyanine green as a fluorescent dye to highlight the thoracic duct during oesophectomy. Conditions: Chylothorax, Esophageal Cancer, Thoracic Duct Intra-Operative Injury Intervention / Treatment: DRUG: Indocyanine Green Location: United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: OTHER Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Participant is willing and able to give informed consent for participation in the study. * Male or Female, aged 18 years or above. * Undergoing elective oesophagectomy Exclusion Criteria: * Known allergy to iodine or ICG * Female patient who is pregnant, planning pregnancy or breastfeeding * Patient has a lactose intolerance (excluded only from receiving cream method) * Known significant liver failure

Study Objectives This phase II trial studies how well pembrolizumab, ipilimumab, and aspirin work in treating patients with melanoma that has spread to other places in the body or cannot be removed by surgery. Monoclonal antibodies, such as pembrolizumab and ipilimumab, may interfere with the ability of tumor cells to grow and spread. Aspirin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab, ipilimumab, and aspirin may work better in treating patients with melanoma. Conditions: Stage III Cutaneous Melanoma, Stage IIIA Cutaneous Melanoma, Stage IIIB Cutaneous Melanoma, Stage IIIC Cutaneous Melanoma, Stage IV Cutaneous Melanoma Intervention / Treatment: DRUG: Aspirin, BIOLOGICAL: Ipilimumab, OTHER: Laboratory Biomarker Analysis, BIOLOGICAL: Pembrolizumab 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 histologically confirmed melanoma that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 * Leukocytes >= 3,000/microliter (mcL) * Absolute neutrophil count >= 1,500/mcL * Platelets >= 100,000/mcL * Total bilirubin within normal institutional limits * Total bilirubin =< 1.5 X institutional upper limit * Aspartate aminotransferase (AST) [serum glutamic-oxaloacetic transaminase (SGOT)] =< 2.5 X institutional upper limit of normal * Alanine aminotransferase (ALT) [serum glutamate pyruvate transaminase (SGPT)] =< 2.5 X institutional upper limit of normal * Creatinine =< 1.5 X upper limit of normal (ULN) * Women of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study drug; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Women of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study medication; Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject * Men of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy; Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject * Ability to understand a written informed consent document, and the willingness to sign it Exclusion Criteria: * Any mental or physical condition or disease or past medical history that mitigates against following the protocol * History of active autoimmune diseases such as but not limited to Crohn?s disease, ulcerative colitis, Sjogren's syndrome, requiring active immune suppression; patient may have hay fever or controlled asthma * Any solid organ transplant or bone marrow transplant * Any other disseminated malignancy. Exceptions include: localized prostate cancer, basal or squamous cell skin cancer, localized cervical cancer, and localized breast cancer. * Uncontrolled central nervous system (CNS) metastasis; patients with CNS metastasis can be eligible if definitively treated with radiotherapy or surgery * Any coexistent medical condition interfering with drug absorption * History of gastritis or malabsorption syndrome or aspirin intolerance or allergy * Live vaccination within the last 30 days * History of multiple sclerosis, type 1 diabetes mellitus (DM) or Guillain-Barre syndrome * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment

Study Objectives Pancreatic ductal adenocarcinoma (PDAC) is the fifth leading cause of cancer-related death in Western countries, and its incidence has increased over the last 40 years. Curative surgery to manage PDAC is possible in only a fraction of patients; indeed, a vast majority (85%) of patients is diagnosed with locally advanced tumors and/or metastases because they lack specific symptoms and early markers for this disease. For these patients, palliative armamentarium consists of conventional chemotherapeutic agents such as Gemcitabine and, more recently, FOLFIRINOX, which offer marginal survival benefits. Consequently, the prognosis for PDAC is still very poor and there is great need for new treatments that can change this poor outcome. In this context, the investigators have devised, in the past few years, a highly innovative approach based on therapeutic gene transfer, which does not rely on a specific genetic and/or cellular background to inhibit PDAC tumor growth. the investigators found that SSTR2 and DCK::UMK gene transfer demonstrated complementary therapeutic effects to inhibit tumor progression and dissemination, and reduced tumor burden, respectively. On the basis of these promising preclinical data, the investigators conducted past three years the first clinical study of non-viral vector-mediated therapeutic gene delivery, guided by endoscopy (EUS), and combined with standard Gemcitabine therapy in patients with locally advanced and metastatic PDAC. The phase 1 demonstrated that the gene-therapy product CYL-02 is expressed in PDAC tumors (with long-lasting expression within tumor tissues), is distributed within the bloodstream in some extent, when combined with Gemcitabine it can inhibit primary-tumor progression and dissemination. Our results tend to demonstrate therapeutic efficacy, especially in patients with locally advanced tumors. Based on these encouraging results, the investigators propose that patients with locally advanced PDAC at the time of diagnosis may clinically benefit from this approach. This phase II study is designed to compare the efficacy of intra-tumoral gene delivery of CYL-02 plus Gemcitabine treatment or Gemcitabine alone in patient with locally advanced PDAC. Conditions: Pancreatic Adenocarcinoma Intervention / Treatment: DRUG: Gene Therapy product CYL-02, DRUG: Gemcitabine Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically or cytologically proven local advanced pancreatic adenocarcinoma patients, * Non metastatic locally advanced non resectable CP assessed after multidisciplinary staff* and/or surgery, * Patient without metastasis, * No previous antitumor treatment or pancreatic resection, * OMS status <= 2, * Measurable tumor according RECIST criteria v 1.1, * Patient that give their informed consent, * Patient older than 18 years of age, * Patients no contraindication of general anaesthesia, * Patient with primary pancreatic tumour accessible to EUS (no digestive stenosis or stomach resection). (*: at least oncologist, radiologist, digestive surgeon and gastroenterologist) Exclusion Criteria: * Patients with metastatic pancreatic tumors disease, * Contraindication of Gemcitabine infusion, * Non-measurable primary tumour (less than 2 cm in size), * Borderline tumour according, * Tumour eligible to a possible neo-adjuvant treatment by radio-chemotherapy or chemotherapy (after multidisciplinary staff*), * Contraindication to EUS-guided fine needle aspiration biopsy (coagulation disorders), * Patient in exclusion period or participating in another clinical research protocol, * Patient that cannot understand or read the information form / consent or is not being able to take the decision to participate to the study, * Pregnant woman, or of childbearing potential not using contraception, * Patient under judicial protection, guardianship or curatorship, * Patient with cystic tumor or pancreatic pseudocyst, * Patient bearing solid tumors other than adenocarcinoma of the pancreas (endocrine tumor, metastasis), * Granulocytopenia: granulocytes <1000/mm3, * Thrombocytopenia: platelet count <100 000/mm3, * Patient not effectively treated for malignant jaundice (biliary stent or bypass) if present at diagnosis. (*: at least oncologist, radiologist, digestive surgeon and gastroenterologist)

Study Objectives This study will examine biomarkers involved in osteomimicry in bone metastases and circulating tumor cells (CTCs) of men with mCRPC before and during therapy with the bone-targeting radiopharmaceutical radium-223. This study will also examine the bio-distribution of radium-223 in bone and bone metastases of men with mCRPC. The investigators hypothesize that bone metastases and CTCs in men with mCRPC will commonly express markers of EMT/plasticity and osteomimicry, not just in the normal surrounding osteoblastic stroma but in the epithelial tumor cells themselves and that radium-223 will target both of these compartments including the more mesenchymal/osteoblastic tumor cells and the surrounding osteoblasts in the active bone microenvironment, with a relative sparing of normal bone and bone marrow. Conditions: Bone Metastatic Castration-Resistant Prostate Cancer Intervention / Treatment: DEVICE: Biomarker analysis, DRUG: Administration of radium-223 Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: EARLY_PHASE1 Primary Purpose: BASIC_SCIENCE Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Age >= 18 years. * Life expectancy of at least 12 weeks (3 months). * Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure. * Histologically confirmed diagnosis of adenocarcinoma of the prostate. Histologic variants of prostate cancer, including neuroendocrine features are permitted; however, pure small cell carcinoma of the prostate is excluded. * Presence of >2 sites of metastatic disease in bone as determined by bone scan or CT, and for men who opt-in for bone biopsy, they must have at least one site amenable to radiographically-guided metastatic biopsy as determined by the study radiologist. * Symptomatic castration-resistant bone metastatic disease as determined by the provider. * Prior or concurrent therapy with either abiraterone acetate or enzalutamide. * Ongoing ADT using an LHRH agonist (e.g. leuprolide, goserelin) or antagonist (e.g. degarelix) must continue on therapy unless prior bilateral orchiectomy has been performed. * Current evidence of disease progression as evidenced by one of the following: 1. 2 consecutive rising PSA levels separated at least 1 week apart above nadir PSA on last systemic therapy. If no nadir, then 2 rising PSA values greater than baseline pretreatment value is required from the most immediate prior therapy, OR 2. CT or bone scan based evidence of disease progression with bone metastasis (new lesions or growth of existing lesions), OR 3. Evidence of symptomatic progression (increased pain in an area with known lesions confirmed on imaging). * All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 Grade 2 or less. * Men of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 30 days after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate. * Acceptable hematology and serum biochemistry screening values: * White Blood Cell Count (WBC) >= 3,000/mm3 * Absolute Neutrophil Count (ANC) >= 1,500/mm3 * Platelet (PLT) count >= 100,000/mm3 * Hemoglobin (HGB) >= 9.0 g/dl * Total bilirubin level <= 1.5 x institutional upper limit of normal (ULN) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 x ULN * Creatinine <= 1.5 x ULN * Albumin > 2.5 g/dL * Willing and able to comply with the protocol, including follow-up visits and examinations Exclusion Criteria: * Treatment with cytotoxic chemotherapy within previous 4 weeks, or failure to recover from AEs down to grade 2 or less due to cytotoxic chemotherapy administered more than 4 weeks previous (however, ongoing neuropathy is permitted) * Receiving concurrent systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188) for the treatment of bony metastases. Prior therapy with radium-223 is not permitted. * Other malignancy treated within the last 3 years (except non melanoma skin cancer or low-grade superficial bladder cancer) * Visceral (i.e. liver, lung, etc) metastases (pulmonary nodules <=1cm are permitted) as assessed by chest, abdominal or pelvic computed tomography (CT) (or other imaging modality) * Presence of active untreated CNS parenchymal or epidural spinal metastases * Lymphadenopathy exceeding 3 cm in short-axis diameter * Imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Treatment should be completed for spinal cord compression. * Any other serious illness or medical condition, such as but not limited to: * Any infection >= National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 Grade 2 * Cardiac failure New York Heart Association (NYHA) III or IV * Crohn's disease or ulcerative colitis * Bone marrow dysplasia * Fecal incontinence * Inability to comply with the protocol and/or not willing or not available for follow-up assessments. * Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation. * Concurrent cytotoxic chemotherapy or anticancer therapies other than abiraterone, prednisone or other glucocorticoids, enzalutamide, androgen deprivation therapy, bisphosphonates, and denosumab. * Concurrent use of another investigational drug or device therapy (i.e., outside of study treatment) during, or within 2 weeks of treatment initiation. * Major surgery within 30 days prior to start of study drug.

Study Objectives A Phase I/IIa, open-label, uncontrolled study to evaluate the safety and efficacy of Astarabine (BST-236) as single agent in patients with refractory or relapsed Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) disease Conditions: Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia Intervention / Treatment: DRUG: Astarabine (BST-236) Location: Israel Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * A. Relapsed or refractory acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), based on World Health Organization Classification; Patients must have morphological proof of AML or ALL with blasts in peripheral blood (PB) or 5% in bone marrow (BM) within 2 weeks prior to study registration. I. Refractory disease will be considered failure to either respond to induction chemotherapy and/or salvage therapy. II. 2nd relapse III. Relapse following autologous or allogeneic stem cell transplantation. B. patients which at the physician discretion are not eligible for standard chemotherapy, whether induction or consolidation, due to age or significant co-morbidities * Age >=18 years. * Ability to understand and willingness to sign the written informed consent document. * Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment and use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * Male subject agrees to use an acceptable method for contraception for the duration of the study. * Eastern cooperative oncology group (ECOG) performance status <= 2 * Hydroxyurea is permitted to control high white blood cells (WBC) count prior to study entry. * Previous treatment related toxicities must have resolved to less than Grade 2 (excluding alopecia). Exclusion Criteria: * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. l. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, uncontrolled hypertension, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant. * Patients with compromised pulmonary function who needs oxygen therapy. * Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results. * Patients who have had chemotherapy (except for hydroxyurea), biologic therapy, immunotherapy, or radiotherapy within 2 weeks of induction therapy or 4 weeks of consolidation or intensive therapy (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. * Patients receiving any other investigational agents. * Patients who have had any surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin biopsy) within 14 days of Day 1. * Serious medical or psychiatric illness likely to interfere with participation in this clinical study. * Patients with prior malignancy are eligible; however, the patient must be in remission from the prior malignancy and have completed all chemotherapy and radiotherapy at least 6 months prior to registration and all treatment-related toxicities must have resolved. * Leptomeningeal/ central nervous system involvement with AML; a lumbar puncture does not need to be performed unless there is clinical suspicion. * Patients with active central nervous system disease or with granulocytic sarcoma as sole site of disease. * Patients who have had prior pulmonary radiation. * Liver enzymes (AST and alanine aminotransferase (ALT) more than 2.5 times the upper limits of normal (ULN), and total bilirubin more than 1.5 x ULN within 14 days of enrollment. * Renal function: Serum creatinine more than 1.5 x ULN within 24 hours of enrollment. * Existence of inter-current organ damage or medical condition that would prohibit or interfere with study drug therapy. * If the patient has co-morbid medical illness, life expectancy attributed to this must be greater than 3 months. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to Astarabine/Ara-C. * Pregnant women are excluded from this study because Astarabine/Ara-C are agents with the 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 Astarabine, breastfeeding should be discontinued if the mother is treated with Astarabine. * known history of Human immunodeficiency virus (HIV) or active hepatitis B or C * Concurrent use of the following medications: Digoxin, Gentamycin, fluorocytosine, L-asparginase, any drugs or supplements that interfere with blood clotting can raise the risk of bleeding during treatment with Ara-C. These include: vitamin E, non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, warfarin, ticlopidine, clopidogrel.

Study Objectives Evaluation of the potential perpetrator effect of BAY1841788 (ODM-201) on rosuvastatin pharmacokinetics. PK of BAY1841788 (ODM-201) after single and repeated administration in male and female subjects. Conditions: Healthy Volunteers, Pharmacokinetics, Drug Interaction Intervention / Treatment: DRUG: Rosuvastatin, DRUG: BAY1841788 (ODM-201) Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Healthy subject - as determined by medical history, physical examination and all procedures required by this protocol. * Age: 45 to 65 years at the screening visit. * Race: White. * Body mass index (BMI): >=18.0 and <=29.9 kg/m*2. * Adequate venous access (frequent blood sampling). * Ability to understand and follow study-related instructions. * Females have to be in postmenopausal state, revealed by: Medical history, if applicable (natural menopause at least 12 months prior to first study drug administration; or surgical menopause by bilateral ovariectomy at least 3 months prior to first study drugadministration) and follicle stimulating hormone (FSH) >40 IU/L at screening examination. * Male subjects must agree to use condoms as an effective contraception barrier method during the whole study (starting after informed consent) and for 3 months after the end of treatment with BAY1841788 (ODM-201). In addition, participants must agree to utilize a second reliable method of contraception simultaneously. The second method which has to be used by a female partner of childbearing potential can be one of the following methods: diaphragm or cervical cap with spermicide or intra-uterine device or hormone-based contraception. Exclusion Criteria: * Medical and surgical history * Subjects with clinically relevant findings in medical history e.g. history or currently existing relevant diseases of vital organs, central nervous system (for example seizures) or other organs (e.g. diabetes mellitus). * Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal. * Febrile illness within 1 week before the first study drug administration. * A medical history of risk factors for Torsades de Pointes (e.g. family history of Long QT interval in electrocardiogram Syndrome) or other arrhythmias. * History of myopathia after treatment with statins. * History of rhabdomyolysis or myopathia. * Medical history of any type of psychiatric disorder, especially mood disorders including medical history with suicidal ideation and/or suicide attempts. * History of thyroid disorders, especially hypothyreosis. * History of respiratory disorder (excluding history of bronchitis or pneumonia). * History of myasthenia. * History of muscle pain or muscle ache, muscle soreness of unknown origin or on frequent occasions although an origin might have been found. * History of any clinically significant hypoglycemia or hyperglycemia. * Relevant hepatic disorders like a history of viral hepatitis, cholestasis, disturbances of bilirubin metabolism, any progressive liver disease. * Relevant renal disorders like recurrent glomerulonephritis, renal injury, and renal insufficiency. However, a history of a single episode of uncomplicated nephrolithiasis will not prevent participation.

Study Objectives This study is designed as a Phase III, multicenter trial, comparing progression-free survival (PFS) after autologous hematopoietic stem cell transplantation using a standard Rituxan plus BEAM transplant regimen versus a regimen adding Bexxar to BEAM. Conditions: Lymphoma, B-Cell, Lymphoma, Large-Cell, Immunoblastic, Lymphoma, Non-Hodgkin Intervention / Treatment: DRUG: Autologous transplantation using rituxan/BEAM, DRUG: Autologous transplantation using Bexxar/BEAM Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Diagnosis of persistent or recurrent REAL classification diffuse large B-cell lymphoma, composite lymphoma with more than 50% diffuse large B-cell lymphoma, mediastinal B-cell lymphoma * Demonstration of CD20+ on at least one histologic specimen * 18-80 years old at time of first registration * Three or fewer prior regimens of chemotherapy over the entire course of their disease treatment (including one induction chemotherapy and no more than 2 salvage chemotherapies); monoclonal antibody therapy and involved field radiation therapy will not be counted as prior therapies * Disease status of primary induction failure, first relapse, or second complete remission; all patients must have chemosensitive disease as demonstrated by response to induction or salvage chemotherapy with at least a partial response (as defined in the protocol) * No more than a 20% bone marrow involvement * Patients with adequate organ function as measured by: * Cardiac: American Heart Association Class I: Patients with cardiac disease but without resulting limitation of physical activity; ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain; additionally, patients greater than 60 years of age must have a left ventricular ejection fraction at rest of at least 40% demonstrated by Multi-Gated Acquisition Scan (MUGA) * Hepatic: Bilirubin less than 2.0 mg/dL (except for isolated hyperbilirubinemia attributed to Gilbert syndrome) and alanine transaminase (ALT) and aspartate transaminase (AST) less than 3x the upper limit of normal * Renal: Creatinine less than 2.0 mg/dL or creatinine clearance (calculated creatinine clearance is permitted) more than 40 mL/min; no hydronephrosis on CT scan prior to mobilization * Pulmonary: Carbon Monoxide Diffusing Capacity (DLCO), Volume forcibly exhaled in one second (FEV1), forced vital capacity (FVC) at least 45% of predicted (corrected for hemoglobin) * Autologous graft with a minimum of at least 1.5 X 10^6 CD34+ cells/kg (target greater than 2.0 X 10^6 CD34+ cells/kg. Peripheral blood stem cells (PBSC) are preferred; however, if PBSC mobilization fails, cells can be obtained by institutional practices (in cases where bone marrow will be used for transplantation, the required CD34+ dose does not apply and institutional practice for total nucleated cell dose should be used). * Initiate conditioning therapy within 3 months of mobilization * Signed informed consent Exclusion Criteria: * Karnofsky performance score less than 70% * Transformed follicular lymphoma * Uncontrolled bacterial, viral, or fungal infection (currently taking medication and with progression or no clinical improvement) * Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ; cancer treated with curative intent less than 5 years previously will not be allowed unless approved by the Medical Monitor or Protocol Chair; cancer treated with curative intent less than 5 years previously will be allowed * Pregnant (positive β-HCG) or breastfeeding; this patient population is excluded due to the lack of data on the use of Bexxar in patients who are pregnant or breastfeeding * Seropositivity for HIV; this patient population is excluded due to the lack of data on the use of Bexxar in HIV positive patients and because the treatment regimens are too immunosuppressive for this patient population * Fertile men or women unwilling to use contraceptive techniques from the time of initiation of mobilization until six-months post-transplant * Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT) * Patients with evidence of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) or abnormal cytogenetic analysis indicative of MDS on the pre-transplant bone marrow examination * Patients with a prior severe reaction to Rituxan or Filgrastim (G-CSF). Patients with severe reactions to G-CSF that receive pre-medication for control of the reaction are not excluded from study. * Patients who have received prior radioimmunotherapy * Patients with known hypersensitivity to murine proteins

Study Objectives The purpose of this study is to evaluate the feasibility, safety, and tolerability of administering ZYC300 with Cyclophosphamide (Cytoxan). Conditions: Breast Cancer, Ovarian Cancer, Prostate Cancer, Colon Cancer, Renal Cancer Intervention / Treatment: DRUG: Cyclophosphamide & ZYC300 (ZYC300 with cyclophosphamide pre-dosing) 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: To be included in the study, patients must meet the following criteria: * Patients with: Advanced stage malignancies who have failed treatment, including at least one, but no more than two, prior regimens of chemotherapy: Ovary, Breast, Colon, Hormone Refractory Prostate Cancer (HRPC), and renal. * Evidence of measurable disease by clinical or radiographic assessment or by tumor biomarker (ovarian and prostate cancer). * Age >= 18 years old. * A baseline Eastern Cooperative Oncology Group Performance Status of 0 or 1. * A life expectancy > 6 months. * Adequate hematological function established within 14 days prior to receipt of the first dose of cyclophosphamide, defined as: 1. Absolute lymphocyte count >= 1,000/mm^2 2. WBC >= 3,000/mm^2 3. Platelet count >= 75,000/mm^2 4. Hemoglobin >= 9 g/dL * Adequate renal function established within 14 days prior to receipt of the first dose of cyclophosphamide, defined as serum creatinine <= 1.5 X upper limit of normal. * Adequate hepatic function established within 14 days prior to receipt of the first dose of cyclophosphamide, defined as: 1. Total bilirubin <= 1.5 X upper limit of normal, and 2. SGOT and SGPT <= 2.5X upper limit of normal. * An MRI of the brain, if clinically indicated, which is negative for parenchymal central nervous system metastases within 28 days prior to receipt of the first dose of cyclophosphamide. If a patient cannot undergo an MRI because of a medical contraindication, a contrast CT of the brain will be acceptable. * A negative pregnancy test (blood or urine) within 14 days prior to first dose of cyclophosphamide (where applicable). * Agree to use appropriate contraception from study entry until the end-of-observation visit. * A signed informed consent form approved by the Institutional Review Board. Exclusion Criteria: Patients cannot participate in the study if any of the following apply: * Have a history of parenchymal brain metastases. * Have received any of the following within 28 days prior to receiving the first dose of cyclophosphamide: 1. Chemotherapy 2. Radiation therapy 3. Immunotherapy 4. Systemic immunosuppressive drugs 5. Glucocorticoids (inhalers for asthma are permitted) 6. Investigational agent or experimental therapy * Have received three or more biologic/targeted therapies, such as monoclonal antibodies and tyrosine kinase inhibitors. * Have initiated or reinitiated the use of hormonal agents within 28 days prior to receiving the first dose of cyclophosphamide. These drugs are allowed if treatment was initiated greater than 28 days prior to receipt of the first dose of cyclophosphamide. * Have a history of bone marrow or stem cell transplantation. * Have a history of treatment with fludarabine, 2-chlorodeoxyadenosine, 2-deoxycoformycin or similar compounds. * Have a history of treatment with chronic systemic immunosuppressive drugs. * Have an immunologic disorder such as immunodeficiency or other chronic auto-immune disease if deemed to be clinically significant. * Have an active systemic infection requiring treatment. * Are known to be positive for HIV antibody. * Pregnant or lactating. * Have a history of alcohol abuse, illicit drug use, or psychiatric disorder that would in the Investigator's opinion jeopardize protocol compliance or compromise the patient's ability to give informed consent. * Have had prior ex vivo or in vivo DNA therapy (administration of viral vectors or plasmid DNA formulations) or cancer vaccines. * Previous exposure to ZYC300 or amolimogene (HPV E6E7 plasmid; formerly known as ZYC101a). Please note: There may be additional inclusion/exclusion criteria. The study center will determine if patients meet all of the criteria. If patients do not qualify for the trial, study personnel will explain the reasons. If patients do qualify, study personnel will explain the trial in detail using an IRB-approved informed consent, and answer any questions. Patients can then decide if they wish to participate.

Study Objectives RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. PURPOSE: Phase I trial to study the effectiveness of vaccine therapy in treating patients who have advanced kidney cancer. Conditions: Kidney Cancer Intervention / Treatment: BIOLOGICAL: dendritic cell vaccine therapy, PROCEDURE: conventional surgery Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT

Inclusion Criteria: * Histologically confirmed metastatic renal cell carcinoma Evaluable or bidimensionally measurable disease with primary renal tumor in place or surgically accessible metastatic site greater than 2 x 2 cm * Over 18 * ECOG 0-1 * Hematopoietic: * Hemoglobin at least 10 g/dL (not transfusion dependent) * Platelet count at least 75,000/mm3 * WBC greater than 3,000/mm3 * Hepatic: SGOT/SGPT no greater than 5 times upper limit of normal (ULN) * Alkaline phosphatase no greater than 5 times ULN * PT/PTT no greater than 1.5 times ULN * Bilirubin no greater than 2.5 mg/dL * Renal: Creatinine no greater than 2.0 g/dL * Hepatitis B surface antigen negative * Negative pregnancy test * Fertile patients must use effective contraception * At least 4 weeks since prior immunotherapy * At least 4 weeks since prior chemotherapy * At least 4 weeks since prior radiotherapy * At least 14 days since prior acute therapy for infection Exclusion Criteria: * uncontrolled CNS metastasis * ischemic heart disease that precludes surgery * pulmonary condition that precludes surgery * other underlying condition or allergy that would preclude study * acute viral, bacterial, or fungal infection requiring therapy HIV negative * pregnant or nursing * other acute medical problems that would preclude study * concurrent corticosteroids (oral, topical, inhaled) * prior organ allografts

Study Objectives The goal of this clinical research study is to learn if a combination of the investigational drug oxaliplatin with 5-Fluorouracil (5-FU) (given at the same time as radiation therapy) is as effective as a combination of these two drugs given before and during radiation therapy in the treatment of esophageal or gastroesophageal cancers. The safety of these combinations of therapy will also be compared. Objectives: Primary objective: Compare the Pathologic Complete Response rate and % of patients with \<50% residual cancer in the resected surgical specimen between Arms A and B. Secondary objectives: 1. Compare 1-year and 3-year survival rates, median survival time, R0 resection rates, safety, and local plus systemic relapse rates between Arms A and B 2. Perform exploratory correlative studies on blood, adjacent normal and cancer tissue to assess predictive markers of response and outcome. 3. Evaluate the joint effects, including possible interactive effects, of proton-versus-photon therapy and treatment arm on overall survival, R0 resection rates, safety, and local plus systemic relapse rates. Conditions: Esophageal Cancer, Gastroesophageal Cancer Intervention / Treatment: DRUG: 5-Fluorouracil, DRUG: Oxaliplatin, RADIATION: Radiation Therapy, PROCEDURE: Surgery Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Local regional carcinoma of the thoracic esophagus (squamous cell or adeno) or gastroesophageal junction. * Patients with T1N1, and T2-3 with any N (M1a only) will be eligible. * Normal liver (serum glutamic-pyruvic transaminase (SGPT) < 56µL, Total Bilirubin <1.5 mg/dL), kidney (Creatinine <1.75 mg/dL), and bone marrow functions (AGN >1,500µL, platelet count >100,000/µL). * Performance status 0 or 1. * Signed informed consent by the investigator or their designee and patient. * Medically fit for surgery. * No Celiac (except for the GE junction cancers), supraclavicular, or paraaortic nodal enlargement unless biopsy negative. * None of the celiac nodes should be larger than 2 cm * Male or Female but both sexes must practice adequate contraception while on therapy * >=18 years but less than 76 years * No known allergy to any of the study drugs. * No prior therapy for this cancer. * No significant cancer (defined as non-melanomatous skin cancers and treated cervical cancers) within the past 5 years * New York Heart Association (NYHA) I and II Exclusion Criteria: * Patients with T1N0, T4, or M1b cancer will be excluded * Significant comorbid conditions (defined as uncontrolled diabetes, active angina or heart failure, uncontrolled hypertension, or active psychiatric condition that prevents consistent participation and compliance). * More than grade 1 neuropathy * Unable to comprehend the requirements of the study or comply with it.

Study Objectives The aim of the retrospective study was to further characterize the prevalence of comorbid conditions as well as the use of concomitant medications in newly diagnosed CML patients in a real-world setting. Hematologists from ten Polish hematological tertiary care centers were asked to analyze medical records for all consecutive CML patients diagnosed with chronic phase CML between January 1st 2005 and December 31st 2014. Conditions: Chronic Myeloid Leukemia Intervention / Treatment: OTHER: the prevalence of comorbid conditions Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * 1) age >= 18 years; 2) diagnosis of chronic phase CML between January 1st 2005 and December 31st 2014. Exclusion Criteria: * primary diagnosis of CML in accelerated or blastic phase

Study Objectives The purpose of this prospective, single-institution observational study is to evaluate associations between the pharmacokinetic (PK) parameters for tyrosine kinase inhibitors (TKIs) used to treat chronic phase chronic myeloid leukemia (CML) and clinical outcomes for up to 12 months. The study aims to identify associations between TKI clearance and/or exposure with demographic and clinical patient characteristics, CML milestones, medication toxicities, medication adherence, and germline genetic variants. Because this is an observational study, standard-of-care therapy will not be altered during the course of participation. Blood samples will be collected at each study visit (up to 6 visits) over the course of 12 months to evaluate TKI concentrations, and PK parameters. Blood will also be collected during the first visit to isolate DNA for next generation sequencing (NGS). Demographic information will be collected at baseline, while clinical and medication adherence information will be collected at baseline and then throughout the study. There will be no direct benefit to you for your participation. Risks are minor, but could include bruising, vein irritation, lightheadedness/dizziness, and/or infection from blood draws, as well as potential loss of confidentiality. Conditions: CML, Chronic Phase, CML (Chronic Myelogenous Leukemia, CML - Philadelphia Chromosome, Chronic Myeloid Leukemia, Chronic Myeloid Leukemia, Chronic Phase Intervention / Treatment: DRUG: Bosutinib, DRUG: Dasatinib, DRUG: Imatinib, DRUG: Nilotinib Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Patients who have signed written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information * Patients must be >= 18 years old. * Patients must have been diagnosed with chronic phase CML. * Patients who will start or have already started receiving oral chemotherapy with bosutinib, dasatinib, imatinib, or nilotinib for their diagnosis of CML. Exclusion Criteria: * Patients who have cognitive impairments that could affect informed decision making. * Patients who are prescribed bosutinib, dasatinib, imatinib, or nilotinib in combination with other chemotheapy agents (e.g., hydroxyurea or omacetaxine). * Patients who have undetectable BCR-ABL transcripts. * Patients with a confirmed T315I point mutation in BCR-ABL and/or prescribed ponatinib. * Patients who are incarcerated. * Patients with accelerated or blast phase CML. * Patients diagnosed with, or currently undergoing treatment for a concurrent second primary malignancy.

Study Objectives The objectives of this study is to investigate treatment patterns and outcomes for Sutent and Inlyta in mRCC patients in a nationwide population-based setting in Sweden. Conditions: Kidney Neoplasms Intervention / Treatment: DRUG: sunitinib, DRUG: axitinib Location: Sweden Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * all patients aged >= 18 years with at least one filled prescription of an oral targeted therapy relevant for treating mRCC registered in the Swedish Prescribed Drug Register (PDR) between July 1st 2005 and June 30th 2020. The Anatomical Therapeutic Chemical (ATC) codes for the oral drugs relevant for treating mRCC are the following: L01XE04 (sunitinib), L01XE05 (sorafenib), L01XE11 (pazopanib), L01XE17 (axitinib), L01XE10 (everolimus), L01XE26 (cabozantinib), L01XE34 (tivozantib), L01XE29 (lenvatinib). * The patients identified in the PDR that also are identified in the SCR with the International Classification of Diseases and Related Health Problems (ICD)-7 diagnosis codes I800 or I809 and ICD-10 codes C64.0 and C64.9 from January 1st 2000 until December 31st 2019;excluding ICD-7 code I801 (cancer of the renal pelvis) will be included in the analysis set. Exclusion Criteria: Patients with ICD-7 code I801 will be excluded

Study Objectives To investigate effect of intravesical mitomycin-C(MMC) applied with bladder wall thermotherapy system on reccurrence and progression status of intermediate and high risk non muscle invasive bladder cancer Conditions: Bladder Cancer Intervention / Treatment: DRUG: bladder wall thermotherapy with Mitomycin-c Location: Turkey Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: PREVENTION Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * newly diagnosed or followed as recurrent intermediate-risk non muscle invasive non muscle invasive bladder cancer according to the criteria of European Association of Urology. * newly diagnosed or followed as recurrent high-risk non muscle invasive non muscle invasive bladder cancer according to the criteria of European Association of Urology. * pathology of urothelial carcinoma Exclusion Criteria: * Low bladder capacity (<150ml) * increased post voiding residual urine (>150ml) * untreatable or uncontrollable urinary tract infection * history of urethral stricture * presence of bladder diverticula larger than 1 cm * pathology other than urothelial carcinoma * WHO (World Health Organization) performance status > 2 * upper urinary tract urothelial carcinoma diagnosis

Study Objectives This phase III trial is studying observation to see how well a risk based treatment strategy works in patients with soft tissue sarcoma. In the study, patients are assigned to receive surgery +/- radiotherapy +/- chemotherapy depending on their risk of recurrence. Sometimes, after surgery, the tumor may not need additional treatment until it progresses. In this case, observation may be sufficient. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as ifosfamide and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery. Conditions: Adult Alveolar Soft-part Sarcoma, Adult Angiosarcoma, Adult Epithelioid Sarcoma, Adult Extraskeletal Chondrosarcoma, Adult Extraskeletal Osteosarcoma, Adult Fibrosarcoma, Adult Leiomyosarcoma, Adult Liposarcoma, Adult Malignant Fibrous Histiocytoma, Adult Malignant Hemangiopericytoma, Adult Malignant Mesenchymoma, Adult Neurofibrosarcoma, Adult Synovial Sarcoma, Childhood Alveolar Soft-part Sarcoma, Childhood Angiosarcoma, Childhood Epithelioid Sarcoma, Childhood Fibrosarcoma, Childhood Leiomyosarcoma, Childhood Liposarcoma, Childhood Malignant Mesenchymoma, Childhood Neurofibrosarcoma, Childhood Synovial Sarcoma, Dermatofibrosarcoma Protuberans, Metastatic Childhood Soft Tissue Sarcoma, Nonmetastatic Childhood Soft Tissue Sarcoma, Stage I Adult Soft Tissue Sarcoma, Stage II Adult Soft Tissue Sarcoma, Stage III Adult Soft Tissue Sarcoma, Stage IV Adult Soft Tissue Sarcoma Intervention / Treatment: DRUG: doxorubicin hydrochloride, OTHER: clinical observation, PROCEDURE: therapeutic conventional surgery, RADIATION: 3-dimensional conformal radiation therapy, DRUG: ifosfamide Location: Canada, New Zealand, United States, Australia, Puerto Rico Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Newly diagnosed non-rhabdomyosarcoma soft tissue sarcoma (STS), confirmed by central pathology review via concurrent enrollment on protocol COG-D9902 * Metastatic or non metastatic disease * Meets 1 of the following criteria: * Intermediate (i.e., rarely metastasizing) or malignant STS, including any of the following: * Adipocytic tumor, including liposarcoma of any of the following histology subtypes: * Dedifferentiated * Myxoid * Round cell * Pleomorphic type * Mixed-type * Not otherwise specified (NOS) * Fibroblastic/myofibroblastic tumors, including any of the following: * Solitary fibrous tumor * Hemangiopericytoma * Low-grade myofibroblastic sarcoma * Myxoinflammatory fibroblastic sarcoma * Adult fibrosarcoma* * Myxofibrosarcoma * Low-grade fibromyxoid sarcoma or hyalinizing spindle-cell tumor * Sclerosing epithelioid fibrosarcoma * So-called fibrohistiocytic tumors, including any of the following: * Plexiform fibrohistiocytic tumor * Giant cell tumor of soft tissues * Pleomorphic malignant fibrous histiocytoma (MFH)/undifferentiated pleomorphic sarcoma * Giant cell MFH/undifferentiated pleomorphic sarcoma with giant cells * Inflammatory MFH/undifferentiated pleomorphic sarcoma with prominent inflammation * Smooth muscle tumor (leiomyosarcoma) * Pericytic [perivascular] tumor (malignant glomus tumor or glomangiosarcoma) * Vascular tumor, including angiosarcoma * Chondro-osseous tumors of any of the following types: * Mesenchymal chondrosarcoma * Extraskeletal osteosarcoma * Tumors of uncertain differentiation, including any of the following: * Angiomatoid fibrous histiocytoma * Ossifying fibromyxoid tumor * Myoepithelioma/parachordoma * Synovial sarcoma * Epithelioid sarcoma * Alveolar soft-part sarcoma * Clear cell sarcoma of soft tissue * Extraskeletal myxoid chondrosarcoma ("chordoid type") * Malignant mesenchymoma * Neoplasms with perivascular epithelioid cell differentiation (PEComa) * Clear cell myomelanocytic tumor * Intimal sarcoma * Malignant peripheral nerve sheath tumor * Dermatofibrosarcoma protuberans meeting both of the following criteria: * Non metastatic disease * Tumor must be grossly resected prior to study enrollment * Embryonal sarcoma of the liver * Unclassified STS that is too undifferentiated to be placed in a specific pathologic category (undifferentiated STS or STS NOS) * Gross resection of the primary tumor <= 42 days prior to enrollment required except if any of the following circumstances apply: * Non metastatic high-grade tumor > 5 cm in maximal diameter and gross or microscopic residual tumor is anticipated after resection * Tumor of either high- or- low-grade that cannot be grossly excised without unacceptable morbidity * High-grade tumor with metastases * Patients with metastatic low-grade tumor whose disease is amenable to gross resection at all sites must undergo gross resection of all sites prior to study entry * Patients with a tumor recurrence after a gross total resection are not eligible * Tumors arising in bone are not eligible * Patients with epithelioid sarcoma, clear cell sarcoma, or clinical or radiologic evidence of regional lymph node enlargement must undergo sentinel lymph node biopsies or lymph node sampling to confirm the status of regional lymph nodes* NOTE: *Except in cases where the study radiologist reviews the imaging and indicates that a biopsy is not needed to confirm that the patient has lymph node involvement. * If lymph node biopsies are positive for tumor (or the lymph nodes are classified as positive by the study radiologist), formal lymph node dissection must be done at the time of definitive surgery(prior to study entry for patients assigned to study regimen C) * Patients with metastatic disease must undergo a biopsy to confirm the presence of metastatic tumor if all metastases are < 1 cm in maximal diameter (except in cases where the study radiologist reviews the imaging and indicated that a biopsy is not needed to confirm that the patient has metastatic disease) * Lansky performance status (PS) 50-100% (for patients <= 16 years of age) OR Karnofsky PS 50-100% (for patients > 16 years of age) * Life expectancy >= 3 months * Absolute neutrophil count >= 1,000/mm³* * Platelet count >= 100,000/mm³* * Creatinine clearance or radioisotope glomerular filtration rate >= 70 mL/min (>= 40 mL/min for infants < 1 year of age)* or serum creatinine based on age and/or gender as follows: * 0.4 mg/dL (1 month to < 6 months of age) * 0.5 mg/dL (6 months to < 1 year of age) * 0.6 mg/dL (1 year to < 2 years of age) * 0.8 mg/dL (2 years to < 6 years of age) * 1.0 mg/dL (6 years to < 10 years of age) * 1.2 mg/dL (10 years to < 13 years of age) * 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 years to < 16 years of age) * 1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age) * Patients with urinary tract obstruction by tumor must meet the renal function criteria listed above AND must have unimpeded urinary flow established via decompression of the obstructed portion of the urinary tract * Bilirubin <= 1.5 times upper limit of normal (ULN)* * Shortening fraction >= 27% by echocardiogram* OR ejection fraction >= 50% by radionuclide angiogram* * Not pregnant or nursing (patients undergoing radiotherapy and/or chemotherapy) * No nursing for >= 1 month after completion of study treatment in study regimens C or D * Fertile patients must use effective contraception during and for >= 1 month after completion of study treatment * Negative pregnancy test * No evidence of dyspnea at rest* * No exercise intolerance* * Resting pulse oximetry reading > 94% on room air (for patients with respiratory symptoms)* * Prior treatment for cancer allowed provided the patient meet the prior therapy requirements * No prior anthracycline (e.g., doxorubicin or daunorubicin) or ifosfamide chemotherapy for patients enrolled on arm C or arm D * No prior radiotherapy to tumor-involved sites

Study Objectives The purpose of this study is to determine what side effects CP 870,893 may cause when given with an immune stimulant called Oncovir poly IC:LC along with a melanoma vaccine. The CP 870,893, the Oncovir poly IC:LC and the melanoma vaccine are investigational drugs that have not been combined in patients before, and that have not been approved for sale by the Food and Drug Administration. The Oncovir poly IC:LC is intended to stimulate the body's immune system. Conditions: Melanoma Intervention / Treatment: DRUG: CP 870,893, BIOLOGICAL: Peptides, BIOLOGICAL: Oncovir poly IC:LC 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 meet the following criteria on pre-study examination (within 28 days prior to study drug administration) to be eligible to participate in the study: * Have read, understood, and provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization after the nature of the study has been fully explained * Histologic diagnosis of Stage III (with >= 3 positive lymph nodes) or Stage IV melanoma that has been resected completely (may include mucosal or ocular melanoma) no more than 6 months prior to screening * Human leukocyte antigen (HLA)-A*0201 status as determined by deoxyribonucleic acid (DNA) allele-specific polymerase chain reaction (PCR) assay * Positive staining of tumor tissue with at least one of the following: antibody HMB-45 for gplOO, NY-ESO-l, or MART-I * At least 4 weeks since treatment (surgery, chemotherapy, immunotherapy, radiotherapy) and at least 6 weeks for treatment with nitrosoureas for melanoma, and at least 8 weeks since adjuvant treatment with an anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody for melanoma and recovered from any serious toxicity experienced during treatment * Women must be either: post-menopausal for at least 1 year; surgically incapable of bearing children; or utilizing a reliable form of contraception during the study and for at least 4 months after the final CP 870,893 infusion or vaccination. Women of childbearing potential must have a negative serum hCG- ß pregnancy test conducted during the screening period and have a negative urine pregnancy test conducted on the day of each infusion (prior to the infusion). * Men who may father a child must agree to the use of male contraception for the duration of their participation in the trial and for at least 4 months after the final CP 870,893 infusion or vaccination. * Patients with Stage III resected melanoma rendered free of disease can have failed treatment with, been ineligible for, or refused treatment with a-interferon. * Analgesic therapy must be stable for a period of 14 days prior to infusion of study drug. * Life expectancy >= 6 months * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Patients with resected brain metastases that are off steroids, have no evidence of disease by brain magnetic resonance imaging (MRI) scanning, or computer tomography (CT) of the brain if an MRI cannot be performed, are eligible. * Screening laboratory values must meet the following criteria: white blood cell (WBC): >=2500 cells/mm³; absolute neutrophil count (ANC): >=1500 cells/mm³, Platelets: >=100,000/mm³; Hematocrit: >=30%; Hemoglobin: >=10 g/dL; Creatinine: <=2.0 mg/dL; aspartate aminotransferase (AST): <=3 x ULN; Bilirubin: <=1.0 x upper limit of normal (ULN) (except patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dL); human immunodeficiency virus (HIV): negative; HBsAg: negative; hepatitis C virus (HCV) antibody [anti-HCV Ab]: nonreactive. If reactive, patient must have a negative HCV RNA qualitative PCR. Exclusion Criteria: * Any prior malignancy except for the following: adequately treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or any other cancer from which the patient has been disease-free for at least 5 years. * History of any autoimmune disease, specifically including the following diseases: inflammatory bowel disease or any other autoimmune bowel diseases; systemic lupus erythematosis; rheumatoid arthritis; or any autoimmune ocular diseases. Patients with an autoimmune disease history affecting the pancreas, pituitary, liver, gastrointestinal (GI) tract or adrenals, and prior history of Guillan-Barre and other neurologic conditions felt to be autoimmune in nature are also excluded. * Active infection, requiring therapy, chronic active hepatitis B virus (HBV) or HCV, or confirmed reactivity with HIV tests. * Pregnancy or nursing: due to the possibility that CP 870,893 could have a detrimental effect on the developing immune system of the fetus or infant, exposure in utero or via breast milk will not be allowed. * Systemic hypersensitivity to Montanide ISA 51 (IFA), Montanide ISA 51 VG or any vaccine component * Any underlying medical condition which, in the opinion of the Principal Investigator (PI), will make the administration of study drug hazardous or obscure the interpretation of adverse events. * Any concurrent medical condition requiring the use of systemic, inhaled or topical corticosteroids or the use of immunosuppressive agents (e.g. cyclosporine and its analog, or chemotherapy agents). All corticosteroid use must have been discontinued at least 4 weeks prior to study entry. * Prior treatment with CP 870,893 or any anti-CD40 antibody * Evidence or history of significant cardiac, pulmonary, hepatic, renal, psychiatric or gastrointestinal disease that would make the administration of CP 870,893 unsafe * Concurrent treatment with chemotherapy or other immunotherapy regimens (must be completed at least 4 weeks before Screening; 6 weeks for nitrosoureas); prior treatment with chemotherapy, radiotherapy or other than anti CD40 antibodies will not be an exclusion. * History of prior allogeneic human stem cell or bone marrow transplant * History of prior thromboembolic venous events, or inherited / acquired coagulopathies

Study Objectives RATIONALE: Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: Phase II trial to study the effectiveness of trastuzumab in treating patients who have advanced salivary gland cancer. Conditions: Head and Neck Cancer Intervention / Treatment: DRUG: Trastuzumab 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 * Histologic diagnosis of any of the following malignancies originating from salivary tissue: adenoid cystic carcinoma, mucoepidermoid carcinoma, acinic cell carcinoma, malignant mixed tumor, polymorphous low grade adenocarcinoma, undifferentiated carcinoma, squamous cell carcinoma, adenocarcinoma. * Her2/neu determination: Patients must have overexpression of the Her2/neu protein in the tumor documented by the Dako polyclonal rabbit anti-Her2 antisera assay. Overexpression may be documented by staining of the original paraffin embedded tumor from the time of diagnosis or from material obtained at the time of locoregional or distant recurrence. Overexpression of HER2/neu will be per the Dako Herceptest guidelines. A Score of 2+ or 3+ will be defined as overexpression. All slides will be reviewed by members of the departments of pathology at either the Brigham and Women's Hospital or the Beth Israel Hospital in Boston. * Patients must be incurable on the basis of unresectable local or distant disease as determined by the patient's surgeon. * Patients must have an ECOG performance status of 0 to 1. * Patients must have at least uni-dimensionally measurable disease documented within one month of initiation of treatment. Measurement may be by physical exam or radiologically. Attempts should be made to photo document all tumor sites assessed by physical examination with a metric ruler within the photo for measurement confirmation. * Patients must be willing and able to go through the process of informed consent. * Patients must have a life expectancy exceeding 3 months. * Patients must be at least 18 years old. * Patients must have adequate organ function as defined by the following tests to be performed within 14 days of therapy initiation: * Absolute neutrophil count > 1999 cells x 10 61L * Platelet count > 99,999 cells x 106/L * Hemoglobin >8.5 gm/di or HCT > 25% * Serum creatinine < 1.5 x institutional upper limits of normal (ULN) or creatinine clearance measured by 24 hour urine collection as at least 50% of institutional lower limit of normal. * Total bilirubin <2 x institutional ULN * AST (SGOT) < 2 x institutional ULN * * If from documented liver involvement with cancer, may be up to < 5 x institutional ULN Alkaline Phosphatase < 5 x institutional ULN * * If from documented bone or liver involvement with cancer, no upper limit restriction. * Baseline determination of normal left ventricular ejection fraction as evidenced MUGA or echocardiogram. Exclusion Criteria: * Patients must not have received more than two regimens of cytotoxic chemotherapy for salivary gland cancer. Previous immunologic, hormonal, homeopathic, natural, or alternative medicine therapies are acceptable provided treatment ended greater than 28 days prior to protocol therapy. * Patients must not receive any form (including radiotherapeutic, immunologic, hormonal, homeopathic, natural, or alternative medicine) of anti-neoplastic therapy other than Herceptin while participating in this study. * Patients must not have a history of any non-salivary invasive neoplasm within three years of trial entry, excepting curatively treated non-melanoma skin cancer and cervical cancer. * Pregnant and breast feeding women are not eligible for this study. No pregnancy test is required. Women of childbearing potential must be counseled on the use of effective birth control prior to participation in this study. * Patients with significant active illness (e.g. congestive heart failure, COPD, uncontrolled diabetes, AIDS, previous MI, cardiomyopathies, history of uncontrolled arrhythmias) are not eligible for this study. * Patients who have received anthracyclines (e.g. doxorubicin, daunorubicin, epirubicin) are eligible but must have a baseline MUGA scan documenting normal cardiac contractility (at or above the normal institutional limit) within one month of trial enrollment. The upper limit of doxorubicin exposure should be no more than 360mg1m2

Study Objectives In this research study, the investigators are looking to determine the effectiveness of Pembrolizumab (MK-3475) when given with bevacizumab or when given alone for the treatment of recurrent glioblastoma multiforme (GBM). This study will also test the safety and tolerability of Pembrolizumab (MK-3475) when given alone or with bevacizumab. Conditions: Glioblastoma Intervention / Treatment: DRUG: Pembrolizumab, DRUG: Bevacizumab Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Have histologically confirmed World Health Organization Grade IV malignant glioma (glioblastoma or gliosarcoma). Participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made. * Previous first line therapy with at least radiotherapy and temozolomide * Be at first or second relapse. * Participants must have shown unequivocal evidence for tumor progression by MRI or CT scan. * CT or MRI within 14 days prior to start of study drug. * An interval of at least 4 weeks (to start of study agent) between prior surgical resection or one week for stereotactic biopsy. * An interval of at least 12 weeks from the completion of radiation therapy to start of study drug unless there is a new area of enhancement consistent with recurrent tumor outside the radiation field or there is unequivocal histologic confirmation of tumor progression * Participants must have recovered to grade 0 or 1 or pre-treatment baseline from clinically significant toxic effects of prior therapy (including but not limited to exceptions of alopecia, laboratory values listed per inclusion criteria, and lymphopenia which is common after therapy with temozolomide). * From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies, or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies. Exclusion Criteria: * Current or planned participation in a study of an investigational agent or using an investigational device. * Has a diagnosis of immunodeficiency. * Has tumor primarily localized to the brainstem or spinal cord. * Has presence of diffuse leptomeningeal disease or extracranial disease. * Has received systemic immunosuppressive treatments within 6 months of start of study drug * Requires treatment with high dose systemic corticosteroids defined as dexamethasone > 4 mg/day or bioequivalent for at least 3 consecutive days within 2 weeks of start of study drug. * Has received prior interstitial brachytherapy, implanted chemotherapy, stereotactic radiosurgery or therapeutics delivered by local injection or convection enhanced delivery. * Requires therapeutic anticoagulation with warfarin at baseline; patients must be off warfarin or warfarin-derivative anti-coagulants for at least 7 days prior to starting study drug; however, therapeutic or prophylactic therapy with low-molecular weight heparin is allowed. * Has history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of start of study drug * Has evidence of intratumoral or peritumoral hemorrhage on baseline MRI scan other than those that are grade <= 1 and either post-operative or stable on at least 2 consecutive MRI scans. * Has gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE Grade > 3 within 6 months of start of study drug. * Has a known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug. 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. * Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. * Has evidence of interstitial lung disease or active, non-infectious pneumonitis. * Has an active infection requiring systemic therapy. * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Is pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial * Has a known history of HIV * Has known active Hepatitis B or Hepatitis C * Has received a live vaccine within 30 days prior to the first dose of study drug. * Has a known hypersensitivity to any of the study therapy products. * Has received anti-angiogenic or anti-VEGF targeted agents (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL-184, sunitinib, etc) * Has a history of non-healing wounds or ulcers, or bone refractures within 3 months of fracture * Has a history of arterial thromboembolism within 12 months of start of study drug. * Has inadequately controlled hypertension * Has a history of hypertensive crisis or hypertensive encephalopathy * Has had clinically significant cardiovascular disease within 12 months of start of study drug * Has a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to start of study drug.

Study Objectives RATIONALE: Everolimus plus Cisplatin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: The purpose of this study is to test how effective combining Cisplatin chemotherapy with Everolimus is in treating subjects with triple negative breast cancer who have residual disease after chemotherapy. Conditions: Breast Cancer, Triple Negative Breast Cancer Intervention / Treatment: DRUG: Everolimus 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: * Female patients >=18 years of age. * Clinical/pathological documentation of residual disease after neo-adjuvant therapy. * Patients with synchronous bilateral cancers are eligible only if: * Index cancer is triple-negative, defined as ER-, PR-, and HER2-. * HER2 negative tumors. HER2 negativity must be confirmed by one of the following: * FISH-negative (FISH ratio <2.2), or * IHC 0-1+, or * IHC 2-3+ AND FISH-negative (FISH ratio <2.2). * Estrogen receptor negative and progesterone receptor negative (<10% staining by IHC for estrogen receptor and progesterone receptor). * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. * Adequate hematologic function, defined by: * Absolute neutrophil count 2 >1000/mm3 * Platelet count >=100,000/mm3 * Hemoglobin >9 g/dL * Adequate liver function, defined by: * AST and ALT <=2.5 x the upper limit of normal (ULN) * Total bilirubin <=1.5 x ULN (unless the patient has grade 1 bilirubin elevation due to Gilbert's disease or a similar syndrome involving slow conjugation of bilirubin). * Adequate renal function, defined by: * Serum creatinine <=1.5 x ULN * Complete staging work-up <=24 weeks prior to initiation of study treatment with computed tomography (CT) scans of the chest and abdomen/pelvis (abdomen/pelvis preferred; abdomen accepted), a CT scan of the head or MRI of the brain (if symptomatic), and either a positron emission tomography (PET) scan or a bone scan. * Adequate cardiac function, defined by a left ventricular ejection fraction (LVEF) value of >50% (or normal per institutional guidelines) by MUGA scan or echocardiogram (ECHO). * Patients with previous history of invasive cancers (including breast cancer) are eligible if definitive treatment was completed more than 5 years prior to initiating current study treatment, and there is no evidence of recurrent disease. * Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately. * Patient must be accessible for treatment and follow-up. * Women of childbearing potential must agree to use an acceptable method of birth control to avoid pregnancy for the duration of study treatment, and for 3 months thereafter. * Able to swallow and retain oral medication. * Patient must be willing to undergo breast biopsies as required by the study protocol. * All patients must be able to understand the investigational nature of the study and give written informed consent prior to study entry. Exclusion Criteria: * Women who are pregnant or breastfeeding. * History of previously treated ductal carcinoma in situ (DCIS) is acceptable. * Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. * Known intolerance or hypersensitivity to Everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus); * Previous cancer (with the exception of non-melanoma skin cancer or cervical carcinoma in situ) in the past 5 years. * Patients who have any severe and/or uncontrolled medical conditions such as: 1. unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction <=6 months prior to start of Everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease 2. Symptomatic congestive heart failure of New York heart Association Class III or IV 3. active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable HBV-DNA and/or positive HbsAg, quantifiable HCV-RNA), 4. known severely impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation 88% or less at rest on room air), 5. active, bleeding diathesis; * Patients may not receive any other investigational or anti-cancer treatments while participating in this study. * Concurrent severe, uncontrolled infection or intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements. * Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study. * Inability to comply with study and/or follow-up procedures. * Patients who have received live attenuated vaccines within 1 week of start of Everolimus and during the study. Patient should also avoid close contact with others who have received live attenuated vaccines. Examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines; * Known history of HIV seropositivity; * Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study treatment. Highly effective contraception methods include combination of any two of the following (a+b or a+c or b+c): 1. Use of oral, injected or implanted hormonal methods of contraception or; 2. Placement of an intrauterine device (IUD) or intrauterine system (IUS); 3. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository; 4. Total abstinence or; 5. Male/female sterilization. Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to treatment. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential. * Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or inhaled corticosteroids are allowed;

Study Objectives The purpose of this study is to evaluate the anti-tumor activity of Everolimus among children with recurrent or progressive ependymoma. Recurrent or progressive ependymoma is incurable and has very limited treatment options. The rationale for this study is based upon both pre-clinical and clinical considerations: Immunohistochemistry studies have demonstrated that 20 out of 23 (87%) pediatric ependymomas are immunoreactive for phosphorylated S6, a biomarker that often predicts response to mTOR pathway-targeted therapy. Furthermore, children with with multiply recurrent ependymomas have had objective and durable responses to the mTOR inhibitor, Sirolimus (Rapamune, Pfizer). As a result of this pre-clinical and clinical data, this study will further investigate the activity of an mTOR pathway inhibitor, Everolimus, against children with recurrent or progressive ependymomas. In this study, Everolimus will be administered at a dose and schedule that have previously been demonstrated as safe and effective in children. Children may take Everolimus for up to 2 years on this study, until tumor progression or unacceptable toxicity. Conditions: Recurrent Childhood Ependymoma Intervention / Treatment: DRUG: Everolimus 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 and Age: Ependymoma (WHO grade II) or Anaplastic Ependymoma (WHO grade III) that has relapsed or become refractory to standard therapy. Patients must have had histologic verification of their malignancy at original diagnosis or time of recurrence. Age must be >= 2 years and <= 21 years of age at study entry. * Tumor tissue must be available (from either time of initial diagnosis or relapse) and submitted for central pathology review and correlative biological studies. * Performance status: Lansky >= 50% for patients <= 10 years of age or Karnofsky >= 50% for patients > 10 years of age. * Adequate bone marrow, liver and renal function. * Fasting serum cholesterol <= 300 mg/dL OR <= 7.75 mmol/L AND fasting triglycerides <= 2.5 x the upper limit of normal. 6. Patients must have measurable residual disease, defined as tumor that is measurable in two diameters on MRI. Diffuse leptomeningeal disease is not considered measurable. * Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy prior to participating in this trial. No prior myelosuppressive chemotherapy for 28 days prior to study enrollment. Must not have received craniospinal radiation therapy within 24 weeks prior to study entry and no involved field radiation therapy for 12 weeks prior to study enrollment. If patients received prior monoclonal antibody treatment, at least three half-lives must be elapsed by the time of treatment initiation. No investigational drugs for 4 weeks prior to study enrollment. * MRI of the brain and the complete spine: All patients must have an MRI of the brain and spine that has measurable tumor (not only diffuse leptomeningeal tumor) within two weeks prior to study enrollment. Exclusion Criteria: * Prior treatment with Everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus). * Concommitant use of medications known to have inhibition or induction of CYP3A enzymes. Systemic corticosteroids (e.g., dexamethasone is a CYP3A inducer) are not allowed. Inhaled corticosteroids are allowed. * Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral Everolimus. * Uncontrolled diabetes mellitus as defined by HbA1c > 8% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary.

Study Objectives RATIONALE: Acupuncture and moxibustion may improve well-being and quality of life in patients with lymphedema caused by breast cancer or head, neck, and throat cancer. PURPOSE: This clinical trial is studying how well acupuncture given together with moxibustion works in improving well-being and quality of life in patients with breast cancer or head, neck, and throat cancer who are undergoing standard treatment for lymphedema. Conditions: Breast Cancer, Head and Neck Cancer, Lymphedema Intervention / Treatment: OTHER: Acupuncture and moxibustion Location: United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SUPPORTIVE_CARE Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

INCLUSION CRITERIA: * male or female patients with either breast or head and neck cancer * diagnosis of mild to moderate uncomplicated lymphoedema * age 18 or over * under the care of the lymphoedema service for at leas: * two months (head and neck cancer patients) * three months (breast cancer patients) * no active cancer disease * at least 3 months since prior active cancer treatment (surgery, radiotherapy, chemotherapy, intravenous treatment) * more than 6 months since prior acupuncture treatment * concurrent adjuvant hormonal therapy allowed * concurrent anti-depressant medication allowed provided there has been no change in prescription or dosing within the past 3 months and patient intends to remain on the medication for the duration of study treatment and follow-up * Able to understand and communicate in English * Able to travel to the Lynda Jackson Macmillan Centre for treatment * Able to attend treatment once weekly for at least 7 consecutive weeks * Able to complete outcome measures EXCLUSION CRITERIA: * bilateral breast cancer * advanced cancer disease

Study Objectives This study evaluated the effectiveness and safety of a dosing method for zoledronic acid in preventing skeletal complications in multiple myeloma participants who have been on an intravenous (IV) bisphosphonate for about one to two years. Conditions: Multiple Myeloma Intervention / Treatment: DRUG: zoledronic acid Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: PREVENTION Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Confirmed diagnosis of multiple myeloma * Have been on zoledronic acid or pamidronate for 1-2 years and therapy must have been initiated for osteolytic lesion, bone fracture, spinal compression, or osteopenia due to multiple myeloma * Stable renal function Exclusion Criteria: * Known sensitivity to bisphosphonates * Receiving investigational drugs considered not safe for co-administration or have a significant effect on bone turnover * Current active dental problems * Had bone marrow transplant or blood stem cell transplant within 2 months before study entry or planned transplant within 2 months following enrollment Other protocol-defined inclusion/exclusion criteria may apply.

Study Objectives This is a phase 2 study of the HSP90 inhibitor, STA-9090 (ganetespib) in subjects with stage IIIB or IV non-small cell lung cancer (NSCLC). Conditions: Non Small Cell Lung Cancer Intervention / Treatment: DRUG: STA 9090 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: * Pathologically confirmed diagnosis of Stage IIIB (with pleural effusion) or Stage IV NSCLC with measurable disease by RECIST and evidence of progression * Availability of tissue for analysis * ECOG Performance Status 0 or 1 * Adequate organ function as defined in the protocol. * Must be at least 18 years old and able and willing to sign a written informed consent document Exclusion Criteria: * Poor venous access requiring an indwelling catheter for study drug administration * Women who are pregnant or lactating * Ventricular ejection fraction < or = to 55% at baseline * Any uncontrolled intercurrent illness

Study Objectives The AVAIL-T trial is a trial to find out how effective avelumab is at treating patients with primary T-cell lymphoma that is refratory to or has relapsed following initial treatment. Conditions: T-Cell Lymphoma Relapsed, T-Cell Lymphoma Refractory Intervention / Treatment: DRUG: Avelumab Location: United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Male or female patients aged >= 16 years * Life expectancy > 12 weeks * ECOG performance status <= 2 * Relapsed or refractory* peripheral T-cell lymphoma including the following histologies: peripheral T-cell lymphoma not otherwise specified (PTCL NOS) , angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL), enteropathy associated T-cell lymphoma (EATL), extranodal NK/T- cell lymphoma (ENKL), transformed mycosis fungoides (LCT MF), hepatosplenic T-cell lymphoma (HSTCL) * For all relapsed patients, relapse must be confirmed by tissue biopsy (or bone marrow trephine if no other tissue available). For refractory patients, a biopsy must have been obtained within the last 3 months * Failed at least 1 prior therapy (but no upper limit of prior regimens) * Adequate haematological function defined by at registration: * absolute neutrophil count (ANC) >= 1.0 × 109/L, (unsupported) * platelet count >= 75 × 109/L, (unsupported) * haemoglobin >= 9 g/dL (may have been transfused) * Adequate hepatic function defined by: * total bilirubin level <= 1.5 × the upper limit of normal (ULN) range * AST or ALT levels <= 2.5 × ULN for all patients or AST and ALT levels <= 5 x ULN (for subjects with documented metastatic disease to the liver) * Adequate renal function defined by an estimated creatinine clearance >= 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) * CT measurable disease with at least 1 lesion having short axis > 1.5cm or splenomegaly > 14cm in cranio-caudal length attributable to relapsed/non responding lymphoma * Negative serum pregnancy test at screening for women of childbearing potential. * Highly effective contraception for both male and female patients if the risk of conception exists. (Note: women of childbearing potential and men able to father a child must agree to use 2 highly effective contraception, defined as methods with a failure rate of less than 1 % per year. Highly effective contraception is required from consent, throughout and for at least 60 days after avelumab treatment. * Ability to give informed consent Exclusion Criteria: Patients are not eligible for the trial if they fulfill any of the following exclusion criteria: * All patients with active CNS involvement of lymphoma * Prior organ transplantation, including allogeneic stem cell transplantation * Significant acute or chronic infections including, among others: * Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS), * Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive) * Current use of immunosuppressive medication, EXCEPT for the following: * intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); Systemic corticosteroids at a maximum dose of <= 1 mg/kg of prednisone or equivalent during screening (to be stopped by day 1 of trial treatment); Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). * Active autoimmune disease that might deteriorat e when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible * 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) * Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v 4.03; however, alopecia and sensory neuropathy Grade <= 2 or other Grade <= 2 not constituting a safety risk based on investigator's judgment are acceptable are acceptable * Pregnancy or lactation * Known alcohol or drug abuse * Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to registration), myocardial infarction (< 6 months prior to registration), unstable angina, congestive heart failure (>= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication. * Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study * Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines * Active infection requiring systemic therapy * Major surgery within 4 weeks of trial entry * Patients and partners of childbearing potential not willing to use two methods of effective contraception during and for 60 days after therapy

Study Objectives The goal of this research is to compare the effects on psychological distress between T4 mono replacement group and T4/T3 combination replacement group after total thyroidectomy in thyroid cancer patients. 1. Subjects: * Psychologically distressed patients, such as depression, anxiety, and fatigue patient after total thyroidectomy with thyroid cancer are considered for participation. Screening of distress after total thyroidectomy is used HADS (Hospital Anxiety and Depression Scale) ≥ 8 for depression or anxiety, and MDASI-F (MD Anderson Symptom Inventory -Fatigue) ≥ 4 for fatigue. 2. Randomization: * Using the table of random sampling numbers, patients assign to T4 mono replacement group or T4/T3 combination replacement group. 3. Evaluation for distress: * Assessment will be made baseline, 4 weeks, 12 weeks and 24 weeks to investigate change of psychological distress (depression, anxiety, and fatigue). Level of distress after thyroidectomy will determine using Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) for depression or anxiety, and Brief Fatigue Inventory (BFI) for fatigue. Conditions: Thyroid Cancer, Distress, Depression, Anxiety, Fatigue Intervention / Treatment: DRUG: Comthyroid, DRUG: Synthroid Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Patient who need thyroid hormone replacement therapy after total thyroidectomy for thyroid cancer * HADS (Hospital Anxiety and Depression Scale) >= 8 for depression or anxiety, or MDASI-F (MD Anderson Symptom Inventory -Fatigue) >= 4 * Patient who maintain TSH recommendation range for TSH suppression according to ATA guidelines Exclusion Criteria: * < 19 or >= 70 years old * Communication difficulties or inability to complete the necessary investigations and questionnaires * Inability to understand purpose of the study or disagree of participation * Past history of psychiatric treatment or diagnosis * Lactation or pregnancy * Past medical history of other cancer diagnosis or treatment * Any of severe comorbid medical conditions according to ASA score >= 3

Study Objectives The goal of this clinical research study is to learn if decitabine (given at 3 different doses) can help to control Myelodysplastic Syndrome (MDS). The safety of these 3 treatments will also be studied. Conditions: Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia Intervention / Treatment: DRUG: Decitabine, DRUG: Decitabine, DRUG: Decitabine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * MDS and 5% or more marrow blasts, or IPSS risk intermediate 1-2 or high risk; or chronic myelomonocytic leukemia * Performance status 0-2 (Eastern Cooperative Oncology Group (ECOG) scale); adequate hepatic (bilirubin < 2 mg/dl) and renal functions (creatinine <2mg/dl); New York Heart Association (NYHA) cardiac status III-IV excluded. * Signed informed consent * No prior intensive combination chemotherapy or high-dose ara-C (>= 1g/m2 per dose). Prior biologic therapies, targeted therapies and single agent chemotherapy allowed. * Patients must have been off chemotherapy for 2 weeks prior to entering this study and recovered from the toxic effects of that therapy, unless there is evidence of rapidly progressive disease. Use of Hydroxyurea for patients with rapidly proliferative disease is allowed for the first two weeks on therapy. Exclusion Criteria: * Nursing and pregnant females are excluded. Patients of childbearing potential should practice effective methods of contraception. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * Patients with active and uncontrolled infections * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements

Study Objectives This is a phase II study randomizing patients with stage I with T1 \> 1.5 cm, stage II or III triple negative breast cancer (TNBC) to preoperative cisplatin versus paclitaxel. The study is designed to evaluate the ability of the Homologous Recombination Deficiency (HRD) assay to predict pathologic response to preoperative chemotherapy. Conditions: Triple Negative Breast Cancer Intervention / Treatment: DRUG: Cisplatin, DRUG: Paclitaxel Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Participants must meet the following criteria on screening examination to be eligible to participate in the study * Pathologic documentation of invasive breast cancer by biopsy (FNA alone is not adequate). * AJCC clinical stage I with T1 > 1.5 cm, stage II or III invasive breast cancer. * Participants with multicentric or bilateral disease are eligible if at least one lesion meets stage eligibility criteria for the study and no tumor is HER2-positive. * Tumors must be HER2 negative defined as HER2 0 or 1+ by immunohistochemistry (IHC) assays and /or lack of gene amplification by FISH defined as a ratio < 2 on invasive tumor by local review. * ER and PgR status by IHC must be known. Tumor must be ER and PR negative (<=5% staining) by local review. * Known BRCA1/2 (BReast CAncer) status is not required for study entry. However patients known to have a germline deleterious BRCA1/2 mutation should be encouraged to consider a preoperative trial specifically designed for BRCA1/2 carriers, if available. * Breast imaging should include imaging of the ipsilateral axilla. For subjects with a clinically positive axilla, a needle aspiration, core biopsy or SLN procedure will be performed to confirm the presence of metastatic disease in the lymph nodes. For patients with a clinically negative axilla, baseline assessment of the axilla will be performed at the discretion of the treating investigator. For patients with pathologically positive axillary lymph nodes prior to preoperative therapy, a level I and II lymph node dissection at the time of definitive surgery is recommended. * Patients with a prior history of contra-lateral breast cancer are eligible if they have no evidence of recurrence of their initial primary breast cancer within the last 5 years. * Women >= 18 years of age. 11. ECOG performance status <=1 (see Appendix A). 12. Laboratory Evaluation * Absolute neutrophil count (ANC) >= 1,500 / mm3 * Platelet count >= 100,000/ mm3 * Bilirubin <= 1.5x upper limit of normal (ULN), for patients with Gilbert syndrome, direct bilirubin will be measured instead of total bilirubin * ALT, AST <=3.0 x ULN ALK Phos <2.5 x ULN * Creatinine <= 1.5 mg/dl or creatinine clearance >= 60 cc/min * Hemoglobin >= 9 mg/dl * Use of an effective means of contraception is required in subjects of childbearing potential since study agents are known to be teratogenic. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. * Ability to understand and the willingness to sign a written informed consent document * Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy and did not receive prior chemotherapy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin. * Patient must be willing to undergo mandatory research biopsy and blood draw. Prior to biopsy procedures patients must be able to be off medications that could increase the risk of bleeding Exclusion Criteria: * Participants with axillary adenopathy only are not eligible for this study. * Prior chemotherapy: Prior non-taxane or platinum containing chemotherapy will be allowed if the prior exposure was at least 5 years ago and the exposure is thought not to potentially interact with the primary outcome of the trial or put the patient at undue risk, and should be reviewed with study PI on a case by case basis. * Any prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, radiation or experimental therapy. * Ipsilateral breast recurrence, unless prior treatment consisted of excision alone for DCIS or breast conserving treatment and hormonal therapy for DCIS or invasive breast cancer. * Ongoing use of any other investigational or study agents. * Peripheral neuropathy of any etiology > grade 1 (NCI CTCAE Version 4.0- Appendix B) * Significant hearing loss that would prevent cisplatin administration. * Renal dysfunction for which exposure to cisplatin would be unsafe or require cisplatin dose modification (i.e., Cre > 1.5 mg/dl or GFR < 60 cc/min).

Study Objectives Surgical resection is one of the most important treatments for solid organ cancer. Whereas cancer recurrence and/or metastasis are the major reasons of treatment failure. The outcomes after surgery are mainly dependent on the balance between the immune function of the body and the invasiveness of residual cancer. Preclinical and retrospective studies suggest that anaesthetic techniques and drugs may affect the long-term outcomes in patients undergoing cancer surgery. The investigators hypothesize that epidural anesthesia-analgesia may improve long-term survival in the elderly who undergo major surgery for cancer. Conditions: Elderly Patients, Solid Organ Cancer, Surgical Resection, Epidural Anesthesia, Long-term Outcome Intervention / Treatment: PROCEDURE: Combined epidural-general anesthesia, PROCEDURE: General anesthesia Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * Elderly patients (age 60-90 years); * Scheduled to undergo noncardiac thoracic or abdominal surgery with an expected duration of 2 hours or longer. For those who undergo thoracoscopic or laparoscopic surgery, the expected length of incision must be 5 centimeters or more; * Agree to receive patient-controlled postoperative analgesia. Exclusion Criteria: * Refused to participate; * Previous history of schizophrenia, epilepsy or Parkinson disease, or unable to complete preoperative assessment due to severe dementia, language barrier or end-stage disease; * History of myocardial infarction or stroke within 3 months before surgery; * Presence of any contraindication to epidural anesthesia and analgesia, including abnormal vertebral anatomy, previous spinal trauma or surgery, severe chronic back pain, coagulation disorder (prothrombin time or activated partial prothrombin time longer than 1.5 times of the upper normal limit, or platelet count of less than 80 * 10^9/L), local infection near the site of puncture, and severe sepsis; * Severe heart dysfunction (New York Heart Association functional classification 3 or above), severe hepatic insufficiency (Child-Pugh grade C), or severe renal insufficiency (serum creatinine of 442 umol/L or above, with or without serum potassium of 6.5 mmol/L or above, or requirement of renal replacement therapy); * Any other conditions that were considered unsuitable for study participation.

Study Objectives This is a Phase 2, Open-label, Randomized, Multicenter Study to Investigate the Efficacy, Safety, and Pharmacokinetics of Brivanib in Patients with Previously Treated Advanced Hepatocellular Carcinoma. Conditions: Hepatocellular Carcinoma (HCC) Intervention / Treatment: DRUG: Brivanib 800 mg, QD, DRUG: Brivanib 400 mg, BID Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * 18-75 years, male or female * Histologically or cytologically confirmed or the clinical diagnosis standard confirmed hepatocellular carcinoma (HCC) patients * Failure or intolerance to prior treatment with chemotherapy and/or targeted therapy * Liver function status Child-Pugh Class A or B (score<=7) * ECOG Performance Status score 0 or 1 * Patients must have adequate bone marrow, renal and hepatic function Exclusion Criteria: * Known history or symptomatic metastatic brain * Uncontrolled moderate and severe ascites * With bleeding tendency and thrombosis history * Known history of severe cardiovascular disease * Uncontrollable active infections (>=CTCAE Grade 2) * Pregnant or breastfeeding women

Study Objectives The current standard treatment approach for young patients with Positive Acute Lymphoblastic Leukemia (Ph+ALL) is the combination of a chemotherapy protocol employing four to five cytotoxic agents typically used for ALL together with imatinib. It is recommended to propose allogeneic Standard Induction and Consolidation Therapy (SCT) to all eligible patients with a suitable donor and to continue imatinib with or without additional therapy in patients not undergoing SCT. This protocol is a study for newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia in patients aged 18 to 55 years. The objective of this strategy is to improve the overall results in the treatment of adult ALL with the addition of specific molecules to the common chemotherapeutic schedule. Conditions: Philadelphia Positive Acute Lymphoblastic Leukemia Intervention / Treatment: DRUG: Dasatinib Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Confirmed new diagnosis of Philadelphia chromosome or BCR-ABL positive acute lymphoblastic leukemia * Male or female patients aged 18-55 years * Not previously treated except for prephase (corticosteroids, cyclophosphamide, single dose VCR will be permitted) therapy during establishment of the diagnosis * Signed written inform consent, willingness and ability to comply with all study procedures * Molecular detection of BCR-ABL transcripts * Willingness of women of child-bearing potential (WOCBP) and male subjects whose sexual partners are WOCBP, to use an effective form of contraception (pearl index < 1%), such as complete sexual abstinence, combined oral contraceptive, hormone IUCD, vaginal hormone ring, transdermal contraceptive patch, contraceptive implant or depot contraceptive injection in combination with a second method of contraception like a condom or a cervical cap / diaphragm with spermicide or surgical sterilisation (vasectomy) in male patients or male partners during the study and at least 6 months thereafter. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or surgical sterilization or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). * Negative pregnancy test for women of child-bearing potential. Exclusion Criteria: * Patients with ECOG status > 2 * Patients with QTcF > 470 ms * Cardiac insufficiency NYHA grade III/IV, LEVF < 50%, myocardial infarction within the past 6 months prior to study * Active secondary malignancy requiring treatment * Patients with active, uncontrolled bacterial, viral or fungal infection * Known infection with HIV, Hepatitis B (except post vaccinal profile) or C * Inadequate hepatic functions defined as ASAT or ALAT > 2,5 times the institutional upper limit of normal and total bilirubin > 2 fold the institutional upper limit unless considered to be due to organ involvement by the leukemia * Concurrent severe diseases which exclude the administration of therapy * Expected non-compliance or inability to understand informed consent * Female patients who are pregnant or breast feeding * Treatment with other investigational antileukemic agents after informed consent.

Study Objectives RATIONALE: Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. Stereotactic radiosurgery (SRS) may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Giving sorafenib tosylate together with SRS may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and the best dose of sorafenib tosylate when given together with SRS in treating patients with brain metastases Conditions: Tumors Metastatic to Brain Intervention / Treatment: DRUG: sorafenib tosylate, RADIATION: stereotactic radiosurgery, OTHER: laboratory biomarker analysis 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 cancer with 1-4 brain metastases (except lymphoma or small cell histologies) * ECOG PS 0 or 1 * Patients are candidates for stereotactic radiosurgery as determined by the treating radiation oncologist. Intra-cranial tumors must measure 4cm or less in greatest dimension. Patients may have received prior neurosurgical resection(s) of intra-cranial metastases if their operation(s) was (were) completed at least 6 months prior to study enrollment. Patients may have had prior whole brain radiation therapy (WBRT) if it was completed at least 6 months prior to study enrollment. * Age >= 18 years and willing and able to sign a written informed consent; a signed informed consent must be obtained prior to any study specific procedures * INR < 1.5 or a PT/PTT within normal limits; patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate; for patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly (INR must be therapeutic in the range of 2-3) Subjects must receive 1st dose of sorafenib 5-7 days prior to administration of Stereotactic Radiosurgery. Exclusion Criteria: * Congestive heart failure > class II NYHA; patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months * Unable to undergo brain MRI * CNS metastases from lymphoma or small cell lung cancer * Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy * Uncontrolled hypertension defined as systolic blood pressure > 140mm Hg or diastolic pressure > 90 mm Hg, despite optimal medical management * Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C * Active clinically serious infection > CTCAE v 4.0 Grade 2 * Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months * Pulmonary hemorrhage/bleeding event >= CTCAE v 3.0 Grade 2 within 4 weeks of first dose of study drug * Any other hemorrhage/bleeding event >= CTCAE v 3.0 Grade 3 within 4 weeks of first dose of study drug * Serious non-healing wound, ulcer, or bone fracture * Any drug that results in hepatic enzyme induction such as anti-convulsants (dilantin, depakote, tegretol, phenobarbital); keppra is allowed * Evidence or history of bleeding diathesis or coagulopathy * Any pulmonary hemorrhage CTCAE v 4.0 Grade 2 or higher within 4 weeks of first study drug * Any other bleeding or hemorrhage CTCAE v 4.0 Grade 3 or higher within 4 weeks of first drug * Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug * Use of St. John's Wort or rifampin (rifampicin) within the last 8 weeks * Known or suspected allergy to sorafenib * Any condition that impairs patient's ability to swallow whole pills * Concurrent investigational drugs * Concurrent steroids are allowed if Dexamethasone dose is =< 16mg daily; if feasible, steroids should be weaned off once sorafenib has been initiated * Prior therapy with sorafenib or other tyrosine kinase inhibitors within the last 12 months; patients are allowed to have been on prior bevacizumab therapy as long as it was stopped at least 6-8 weeks prior to enrolling on this trial * Any malabsorption problem * Hemoglobin =< 9.0 g/dl * Absolute neutrophil count (ANC) =< 1,500/mm^3 * Platelet count =< 100,000/mm^3 * Total bilirubin >= 1.5 times upper limit of normal (ULN) * ALT and AST >= 2.5 times the ULN ( =< 5 x ULN for patients with liver involvement) * Creatinine >= 1.5 times ULN * Women of childbearing potential with a positive serum pregnancy test performed within 7 days prior to the start of treatment; women and men of childbearing potential that do not agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation; men who do not agree to use adequate birth control for at least three months after the last administration of sorafenib * All toxicities from prior therapies must have resolved to CTCAE v3.0 Grade I or better by the time of study enrollment

Study Objectives In western countries, melanoma represents a major mistake of public health by its frequency, lethality and the increasing of incidence. Surgery can cure melanoma diagnosed very early. In other cases, it exists a risk of recurrence of lymph node and visceral. At the stage of visceral metastases, the prognosis of melanoma is catastrophic, with a median survival of 6 months. Indeed, the reference chemotherapy by dacarbazine induces a very limited response rate of 10-20%, the ipilimumab which has been authorized in the second intention, has a response rate of 10%, and other available treatments don't have a superior efficiency. Metformin is an oral antidiabetic of biguanides family which acts by inducing the activation of AMPK, a molecule which is inactivated in many cancers including the melanoma. In agreement with these data, several preclinical studies suggested that metformin has antineoplastic activity. In the case of melanoma, a study published recently has showed that metformin inhibits proliferation of melanoma cells in vitro and we confirmed for our part these results in our laboratory (INSERM U895). Conditions: Metastatic Melanoma (Stage IIIC Non-résécable or no Surgically Curable or Stage IV With Classification AJCC) Intervention / Treatment: DRUG: Metformin Group Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Major patients with metastatic melanoma (stage IIIC non-résécable or no surgically curable or stage IV with classification AJCC) in progression after a first-line of treatment by vemurafenib or chemotherapy, and non-eligible or non-responders to ipilimumab. Metastases measurable by RECIST criteria. Hematologic, renal and hepatic appropriate functions. Negative pregnancy test. Exclusion Criteria: * Patients with symptomatic brain metastases and Performans Status (PS)>2. Patients with carcinomatous meningitis. Pregnant or breathfeeding women. Patients with a contraindication to the metformine. HIV infection, active infection with HBV or HCV. Patients already treated with metformin in the context of diabetes.

Study Objectives The primary objective of this study is to assess the efficacy of nimotuzumab in combination with chemotherapy and radiotherapy for the treatment of locally advanced esophageal cancer, comparing it to that of the conventional treatment with radiation and chemotherapy. The secondary objective of this study is to assess the health-related quality of life for the nimotuzumab in combination with chemotherapy and radiotherapy regimen, compared to the standard chemoradiation regimen in the treatment of inoperable locally advanced esophageal cancer. Conditions: Esophageal Cancer, Adenocarcinoma Intervention / Treatment: DRUG: Nimotuzumab, DRUG: Cisplatin, DRUG: Fluorouracil, RADIATION: Radiotherapy Location: Brazil Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2, PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Age >= 18 years; * Histological prove of SCC or esophageal adenocarcinoma; * T1N1M0, T2N1M0, T3N0M0, T4N0M0, T3N1M0, T4N1M0, qqTqqNM1a stage, according to the TNM system42; * Life expectation above 6 months; * Inoperable superior, medial, or distal third esophageal cancer, including GE junction tumors, defined as type I and II tumors in the Siewert classification43 (see Appendix B); * Performance status 0, 1, or 2, according to the Eastern Cooperative Oncology Group criteria44 (ECOG) (see Appendix C); * Creatinine clearance >= 60 ml/min, according to the Cockcroft and Gault formula45 (see Appendix D); * Adequate body functions, indicated by * Creatinine clearance >= 60 ml/min; * Bilirubin, transaminase, alkaline phosphatase, and gamma-GT < 1,5 x the upper limit of normal; * leucocytes >= 3000/μl; * granulocytes >= 1500/ μl; * hemoglobin >= 9 g/dl; * platelets >= 80000/ μl; * Adequate calorie ingestion, at the investigator's discretion; * He/she must have signed the informed consent form Exclusion Criteria: * Previous or planned treatment of esophageal carcinoma with surgery, radiotherapy, chemotherapy, or antineoplastic biological therapy; * Presence of active infection; * Knowledge of the presence of HIV seropositivity; * Presence of severe comorbidities that, in the investigator's opinion, will put the patient at a significantly higher risk or will damage the protocol compliance; * Presence of a significant neurological or psychiatric disease, including dementia and seizures, as per the investigator's judgment; * History of malignant neoplasm, except for adequately treated skin basal carcinoma or SCC, and cervical carcinoma in situ; * Presence of peripheral neuropathy; * Knowledge of the presence of hypersensitivity or allergy to drugs that will be administered in this protocol; * History of severe allergic reaction; * Pregnancy or lactation; * Presence of aerodigestive fistula (trachea and/or bronchia); * Evident presence of trachea and/or bronchia infiltration by the tumor; * Presence of uncontrolled hypercalcaemia >= 2.9 mmol/L (or grade >1, according to the NCI-CTCAE, version 3.0).

Study Objectives Phase 1, open-labeled, safety and tolerability study for the treatment of subjects with relapsed or refractory solid tumors. Conditions: Solid Tumors Intervention / Treatment: DRUG: BIIB015 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 * Age >= 18 years at the time of informed consent. * Solid tumors that are relapsed or refractory to at least 1 prior anti-cancer systemic therapy and for which no standard therapy exists. * ECOG Performance Status <= 2. Exclusion Criteria * History of keratoconjunctivitis, open or closed angle glaucoma, or "dry eye" disease. * New York Heart Association (NYHA) Grade II or greater congestive heart failure. * History of myocardial infarction within 6 months prior to Day 1. * Presence of >= Grade 2 peripheral neuropathy. * Known presence of central nervous system or brain metastases. * Prior therapy with a conjugated or unconjugated maytansine derivative.

Study Objectives Specific Aim 1: To investigate whether, in Lymphangioleiomyomatosis (LAM) patients, the combination of sirolimus and hydroxychloroquine is safe and well tolerated Specific Aim 2: To investigate whether, in LAM patients, 6 months of combination therapy with sirolimus and hydroxychloroquine results in improvement of indicators of disease, and whether the gains are sustained after stopping therapy. Specific Aim 3: To investigate the potential role of a LAM-specific peripheral blood signature to predict rates of disease progression and determine responsiveness to combination therapy. This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine (200 mg or 400 mg) taken orally daily. Up to 18 adult women with LAM will be enrolled. Conditions: Lymphangioleiomyomatosis Intervention / Treatment: DRUG: "Sirolimus" and "Hydroxychloroquine" 200 mg, DRUG: "Sirolimus" and "Hydroxychloroquine" 400 mg Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: * Female age >= 18 years * Ability to give informed consent * Diagnosis of LAM as defined as typical cystic change on CT plus: * biopsy or cytology of any tissue demonstrating LAM * angiomyolipoma, chylothorax, lymphangioleiomyoma, or tuberous sclerosis * serum VEGFD greater or equal to 800pg/ml * Post-bronchodilator FEV1 equal or less than 80% of predicted or DLCO equal equal or less than 70% of predicted, or RV > 120% of predicted at baseline * Women of childbearing potential must agree to use 2 forms of barrier contraception during and for 8 weeks after the last dose of medication. Exclusion Criteria: * History of intolerance of mTOR inhibitors * History of intolerance to hydroxychloroquine * History of severe psoriasis * History of porphyria cutanea tarda * Uncontrolled intercurrent illness * Pregnant, breast feeding, or plan to become pregnant in the next year * Inadequate contraception * Significant hematological or hepatic abnormalities * Use of an investigational drug within 30 days of study start * Inability to attend scheduled clinic visits * Inability to perform PFTs * Creatinine > 2.5mg/dL * Recent pneumothorax within 8 weeks of screening * History of malignancy in the last 2 years other than basal cell skin cancer * Use of estrogen containing medication within 30 days of screening * Abnormal G6PD levels at baseline * Preexisting maculopathy or retinopathy * Preexisting myopathy * Currently taking doxycycline, metformin, lupron, simvastatin * Unable to undergo CT or MRI * History of seizure within last year * Hepatitis B, C, HIV positive serology * Use of alternative medical therapies for LAM for at least 6 weeks prior to study participation * History of myocardial infarct, angina, or stroke related to atherosclerosis * History of cardiomyopathy * Previous lung transplant * Surgery (involving entry into a body cavity or requiring 3 or more stitches) within 2 months of initiation of study drug * Uncontrolled cholesterol > 350mg/dL, triglycerides > 400mg/dL

Study Objectives The purpose of this study is three-fold: 1) to examine the ability of the experimental drug tariquidar to improve chemotherapy results by blocking a protein (P-glycoprotein) on some cancer cells that acts to pump out cancer drugs; 2) examine how tariquidar interacts with the cancer drug docetaxel; and 3) evaluate the effectiveness of combination treatment with tariquidar and docetaxel in treating patients with lung, ovarian, or cervical cancer. Patients 18 years of age and older with recurrent or metastatic (spreading) lung, cervical, or ovarian cancer who cannot benefit from any standard treatment may be eligible for this study. Candidates will be screened with a medical history and physical examination; review of pathology slides; blood and urine tests; imaging tests, including computed tomography (CT) or magnetic resonance imaging (MRI) scans; chest x-ray, electrocardiogram (EKG); and possibly echocardiogram. Participants will undergo the following tests and procedures: Blood draw. Blood is drawn before treatment begins to establish baseline levels for future blood tests. Blood counts are done twice weekly after chemotherapy begins. Central venous catheter placement. A plastic tube is put into a major vein in the chest. It is used to give the study drugs or other medications, including antibiotics and blood transfusions, if needed, and to withdraw blood samples. The line is usually placed under local anesthesia in the radiology department or the operating room. It can stay in the body for months or be removed after each treatment is completed. Chemotherapy. Treatment cycles are 21 days. Both drugs are given on day 1 of each cycle. First, tariquidar is given as a 30-minute infusion. One hour after the tariquidar infusion, docetaxel is infused over 1 hour. (For the first cycle only, docetaxel is given in divided doses one week apart and tariquidar is administered on either day 1 or day 8. The order of tariquidar administration is randomized to generate optimal pharmacokinetic data. Patients will be hospitalized for several days during this cycle to gather research data). The tariquidar dose remains the same throughout the study. Docetaxel may be increased or decreased from cycle to cycle, based on side effects. Conditions: Lung Neoplasms, Ovarian Neoplasms, Cervix Neoplasms, Renal Neoplasms Intervention / Treatment: DRUG: docetaxel, DRUG: tariquidar, OTHER: 99mTc-sestamibi imaging 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: * Patients must fulfill all of the following criteria to be eligible for study admission: * Age greater than or equal to 18 years. * Histologic or cytologic confirmation of lung, cervical, or ovarian cancer, following at least one standard treatment regimen, and for which there is no known standard therapy capable of extending life expectancy. Female patients with primary papillary carcinoma of the peritoneum and fallopian tube cancers will be included in the latter group, as the disease entities are closely associated with epithelial ovarian carcinoma, can be difficult to distinguish, have a similar epithelial origin, and are treated in an identical manner. * Histologic or cytologic confirmation of renal cell carcinoma (clear cell, type 1 and type II papillary chromophobe, collecting duct and medullary). Patients should have received either sunitinib or sorafenib, unless deemed ineligible for treatment with either agent. In addition,patient should either: (a) have received IL-2; (b) have been evaluated for therapy with Interleukin-2 (IL- 2) and deemed to be ineligible; or (c) have been evaluated for therapy with IL2 and refused treatment. * Performance status: Eastern Cooperative Oncology Group (ECOG) 0-2 * Life expectancy of 3 months or greater. * Suitable candidate for receiving planned therapy as evidenced by screening laboratory assessments hematologic, renal hepatic, and metabolic functions, platelet count greater than or equal to 90,000/mL, absolute granulocyte count(AGC) greater than or equal to 1,500/mL, serum creatinine greater than or equal to 1,500/mL, serum creatine less than or equal to 1.5 mg/dl )or if greater than 1.5 a measured 24 hour creatinine clearance greater than or equal to 50 mL/min) and serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 2.5 x normal limit (NL) and bilirubin less than or equal to 1.5 x NL (in patients with clinical evidence of Gilbert's disease,less than or equal to 3 x NL). * Patients must be greater than or equal to 4 weeks prior radiation or chemotherapy, greater than 2 weeks from hormonal therapy; greater than 4 weeks from prior experimental therapy; greater than 6 weeks from mitomycin C; and greater than 8 weeks from prior UCN01 treatment. * No serious intercurrent medical illness. * Measurable disease by radiographic means or physical examination. For ovarian cancer, assessable disease by cancer antigen 125 (CA125) measurement is allowed. * Willingness to sign a written consent form, and to comply with the protocol. Exclusion Criteria: * The following patient populations are not eligible for this study. * Pregnant or nursing women are not eligible; women of childbearing age must agree to use an effective method of contraception. Pregnant women are not eligible because of teratogenic effects of chemotherapy. * The presence of a second malignancy that has not received primary treatment or would complicate the primary objective of this study. * Patients who are poor medical risk because of active, uncontrolled infection or other nonmalignant systemic disease. * Human immunodeficiency virus (HIV) seropositive patients. Patients infected with the HIV virus will be excluded from this trial because the effect of the combination of tariquidar and docetaxel on HIV replication and/or the immune system is unknown and potentially harmful. * Patients receiving agents which have major interactions with the cytochrome P450 3A4 (CYP3A4)drug metabolizing system and which cannot be discontinued may not be included in the trial. * Untreated brain metastases (or local treatment of brain metastases within the last 6 months) due to the poor prognosis of these patients and difficulty ascertaining the cause of neurologic toxicities.

Study Objectives This is a phase I study to determine the safety, tolerability and recommended phase II dose of ARQ 197 given in combination with erlotinib as primary endpoints in CYP2C19 poor metabolizer patients with advanced/recurrent non-small-cell lung cancer. The pharmacokinetic profile and antitumor activity of ARQ 197 administered alone or in combination with erlotinib will also be determined as secondary endpoints. Conditions: Advanced/Recurrent Non-small-cell Lung Cancer Intervention / Treatment: DRUG: ARQ 197 and Erlotinib Location: Japan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP

Inclusion Criteria: * Voluntary written informed consent for study participation must be obtained * A histologically or cytologically confirmed advanced/recurrent non-small-cell lung cancer * History of >=1 prior chemotherapy regimen (treatment with EGFR tyrosine kinase inhibitors will be counted as one regimen) * ECOG PS of 0 or 1 * Life expectancy of >=3 months * Poor metabolizers as defined by CYP2C19 genotype Exclusion Criteria: * Anti-cancer chemotherapy, anti-cancer therapy with EGFR-TKI, hormone therapy, radiotherapy, immunotherapy, other investigational agents or anti-cancer antibody therapy within 28 days prior to ARQ 197 dose * Surgery for cancer within 28 days prior to ARQ 197 dose * Active double cancer * Known symptomatic brain metastases * An intercurrent illness that is uncontrolled (e.g., infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic arrhythmia, interstitial pneumonia) * Pregnant or lactating * Subjects who wish to have a child and who would not agree to use contraceptive measures

Study Objectives The purpose of this study is to compare the efficacy of ZD6474 and ZD1839 in patients with NSCLC after Failure of Prior Platinum-based Chemotherapy. Conditions: Carcinoma, Non-Small-Cell Lung Intervention / Treatment: DRUG: ZD6474, DRUG: Placebo, DRUG: ZD1839 Location: Germany, United Kingdom, United States, Belgium, Argentina, South Africa Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: DOUBLE

Inclusion Criteria: * Failure of either first-line and/or second-line chemotherapy either of which was platinum-based (the prior regimen must have failed the subject because of toxicity or progression of tumor * Prior histologic or cytologic confirmation of locally advanced or metastatic (IIIB/IV) NSCLC Exclusion Criteria: * Subjects who have received second-line or subsequent chemotherapy * Any evidence of clinically active interstitial lung disease (patients with chronic, stable, radiographic changes who are asymptomatic, need not be excluded)

Study Objectives The purpose of this study is to estimate the time to disease progression when everolimus and pasireotide are given together in patients with advanced or metastatic HCC who have not had any prior systemic therapy. Conditions: Advanced Adult Hepatocellular Carcinoma Intervention / Treatment: DRUG: Everolimus, DRUG: Pasireotide 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: * Each subject must meet all of the following inclusion criteria to participate in this study: 1. Advanced or metastatic hepatocellular carcinoma (stage C per the BCLC criteria, see Appendix A). HCC may be diagnosed by tissue diagnosis or Alpha-fetoprotein (AFP) >400 ng/mL with compatible mass on Magnetic Resonance Imaging Scan (MRI). Cat Scan (CT) abdomen with 3-phase contrast with arterial phase enhancement is acceptable, although MRI is preferred (imaging should be done within 4 weeks of study initiation). Recurrences of previously resected HCC will not require tissue confirmation if there is clear radiographic recurrence in the judgment of the investigator. Disease must not otherwise be amenable to local therapy. 2. Maximum Childs-Pugh score 6 (see Appendix A) with no active encephalopathy 3. Prior systemic therapy limited to sorafenib that was discontinued due to intolerance. Patients must undergo at least a 4-week washout prior to enrollment. 4. Eastern Cooperative Oncology Group (ECOG) PS of 0-2 5. Life expectancy of >12 weeks 6. Age >=18 years 7. Patients who have received previous local therapy, such as surgery, radiotherapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous injection, or cryoablation, will be eligible for enrollment in the study provided that there is documented progression and disease is not amenable to further local therapies. Therapy must be completed >4 weeks prior to study initiation (Day 1 of everolimus and pasireotide administration). 8. Minimum of 4 weeks since any major surgery 9. No active serious infection or other comorbid illness which would impair ability to participate in the trial. 10. International Normalized Ratio (INR) <=1.5. (Anticoagulation is allowed if target INR <=2.0 on a stable dose of warfarin or on a stable dose of low molecular weight heparin (LMWH) for >2 weeks at time of enrollment). 11. Fasting serum cholesterol <=300 mg/dL OR <=7.75 mmol/L AND fasting triglycerides (TGs) <=2.5 x upper limit of normal (ULN). NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication. 12. Patients must have adequate organ function as evidenced by: * Absolute neutrophil count (ANC) >=1.5 x 109/L * Platelet count >=50 x 109/L * Hemoglobin (Hg) >9 g/dL * Bilirubin <=2 x ULN * Aspartate transaminase (AST) or Alanine transaminase (ALT) <=5 x ULN * Serum creatinine <=1.5 x ULN OR creatinine clearance >=50 mL/min (estimated by Cockcroft Gault or measured) 13. Serum magnesium and serum potassium within institutional normal limits (patients may be on replacement) 14. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test performed within 7 days prior to Day 1 of everolimus and pasireotide administration. 15. WOCBP and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men and women should use adequate birth control for at least 8 weeks after the last administration of study drugs. (Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions and are therefore not considered effective for this study.) 16. Signed, Institutional Review Board (IRB) approved written informed consent Exclusion Criteria: * Patients meeting any of the following exclusion criteria at baseline will be excluded from study participation: 1. Patients who have received prior treatment with an mTOR inhibitor (e.g., sirolimus, temsirolimus, everolimus) or somatostatin analog (e.g. octeotride) 2. Chronic treatment with systemic steroids (except for intermittent topical, local injection, or eye drops) or another immunosuppressive agent. NOTE: This restriction regarding systemic steroids does not apply should patient need course of glucocorticoid for treatment of non-infectious pneumonitis during study (see Section 4.5.2). 3. Patients with a known hypersensitivity to everolimus or other rapamycins (e.g., sirolimus, temsirolimus) or to its excipients 4. Patients with a known hypersensitivity to somatostatin or to its excipients 5. Concurrent or planned radiation, hormonal, chemotherapeutic, experimental, or targeted biologic therapy 6. Prior treatment with any investigational drug within the preceding 4 weeks 7. 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 (New York Heart Association [NYHA] 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 spirometry and diffusing capacity for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air * Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN or Glycated hemoglobin (HbA1c) >8.0% (Note: at the principle investigator's discretion, ineligible patients can be re-screened after adequate medical therapy has been instituted.) * Active (acute or chronic) or uncontrolled severe infections. NOTE: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. Hepatitis B viral deoxyribonucleic acid (HBV DNA) and Hepatitis C viral ribonucleic acid (HCV RNA) polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection. See Section 4.2 for further information. 8. Clinically significant third space fluid accumulation (i.e., ascites requiring paracentesis despite use of diuretics) or pleural effusion that either requires thoracentesis or is associated with shortness of breath 9. Risk factors for prolongation of Corrected QT Interval (QTc)* including: * QTc at screening >450 msec * History of syncope or family history of idiopathic sudden death * Sustained or clinically significant cardiac arrhythmias * Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade AV block * Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes or Parkinson's disease), human immunodeficiency virus (HIV), uncontrolled hypothyroidism, or cardiac failure * Concomitant medication(s) known to increase QT interval (See Appendix B) * University of North Carolina at Chapel Hill (UNC) uses GE electrocardiogram (ECG) carts which use the Bazett formula for QTc. 10. Patients should not receive immunization with attenuated live vaccines within 1 week of study entry or during study period. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guérin (BCG), yellow fever, varicella, and TY21a typhoid vaccines. 11. Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases 12. Symptomatic cholelithiasis 13. Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin 14. A known history of HIV seropositivity (HIV testing is not mandatory) 15. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection.) 16. Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except warfarin as long as the goal INR is <=1.5). Low-molecular-weight heparin (LMWH) is permitted (see Section 3.1.10.) 17. Unable or unwilling to discontinue use of prohibited fruit (or its juices) and/or prohibited medications listed in Appendix B for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study 18. Male patient whose sexual partner(s) are WOCBP who are not willing to use adequate contraception during the study and for 8 weeks after the end of treatment 19. Active alcohol intake of 80 grams or more per day. For reference, one portion of alcohol (one glass of wine, one can or bottle of beer, or one ounce of hard liquor) contains approximately 15 grams of ethanol. 20. Inability to comply with study and/or follow-up procedures 21. History of noncompliance to medical regimens

Study Objectives The purpose of this study is to determine if Bortezomib, known commercially as Velcade is safe and tolerated at different dose levels (amounts) with high dose Cyclophosphamide to be used as graft versus host disease prevention after reduced-intensity allogeneic hematopoietic stem cell transplantation. Conditions: Hematological Malignancy Intervention / Treatment: DRUG: Cohort 1-Bortezomib (Velcade ®), DRUG: Cohort 2-Bortezomib (Velcade ®), DRUG: Cohort 3-Bortezomib (Velcade ®) Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: PREVENTION Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria * 8 out of 8 matched related or unrelated donor * Age > 18 years * Good performance status with a Karnofsky score >= to 70% * No evidence of progressive bacterial, viral or fungal infection despite adequate treatment * Creatinine clearance > 40 mL/min/1.72m2 * Total bilirubin < 1.5 and ALT and AST < 2 times the upper limit of normal * Cardiac ejection fraction > 40% * DLCO > 50% * Negative pregnancy test * Negative HIV serology * Able to provide informed consent * Female subject is either postmenopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of bortezomib, or agree to completely abstain from heterosexual intercourse. * Male subjects, even if surgically sterilized (ie, status postvasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse. Exclusion Criteria: * Age <18 years * Poor performance status (<70%) * Active infections * Abnormal creatinine clearance <40ml/min * Elevated bilirubin >1.5 and ALT and AST .2 times the upper limit of normal * Poor ejection fraction <40% * DLCO <50% * Pregnant female. * HIV positive * Inability to provide informed consent * Patient has >= Grade 2 peripheral neuropathy * Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant. * Patient has hypersensitivity to bortezomib, boron, or mannitol. * Serious medical or psychiatric illness likely to interfere with participation in this clinical study. * Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy. * Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.

Study Objectives The purpose of this study is to assess the feasibility of dose-dense doxorubicin and cyclophosphamide followed by eribulin mesylate for adjuvant treatment of early stage breast cancer. Conditions: HER2-normal Intervention / Treatment: DRUG: eribulin mesylate 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 * Male and female subjects aged greater than or equal to (>=) 18 years * Histologically confirmed Stage I to III invasive breast cancer. Subjects may have more than one synchronous primary breast tumor. * HER-2 normal as determined by fluorescence in situ hybridization (FISH) or 0 or 1+ by immunohistochemistry (IHC) staining. * Subject is a candidate for chemotherapy in the adjuvant setting. Adjuvant therapy must begin within 84 days of the final surgical procedure for breast cancer. * Adequate cardiac function, defined by baseline LVEF >=50 percent (%) by Multiple Gated Acquisition (MUGA) scan or echocardiogram. * ECOG performance status of 0 or 1. * Adequate renal function as evidenced by serum creatinine less than or equal to (<=) 1.5 mg/dL or calculated creatinine clearance >=40 mL/min per the Cockcroft and Gault formula. * Adequate bone marrow function as evidenced by ANC >=1.5 x 10^9/L, hemoglobin >=10.0 g/dL, and platelet count >=100 x 10^9/L. * Adequate liver function as evidenced by bilirubin <=1.5 times the upper limits of normal (ULN) and alkaline phosphatase (AP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) <=3 x ULN. * Females of childbearing potential must have a negative urine or beta-human chorionic gonadotropin serum pregnancy test within 2 weeks prior to Cycle 1, Day 1. A urine pregnancy test should be repeated prior to chemotherapy if not conducted within 72 hours of start of treatment. Female subjects of childbearing potential must agree to be abstinent or to use a highly effective method of contraception (e.g., condom + spermicide, condom + diaphragm with spermicide, intrauterine device (IUD), or have a vasectomized partner) having started for at least one menstrual cycle prior to starting study drug and throughout the entire study period and for 30 days (longer if appropriate) after the last dose of study drug. Perimenopausal women must be amenorrheic for at least 12 months to be considered of nonchildbearing potential. Male subjects who are not abstinent or who have undergone a successful vasectomy, who are partners of women of childbearing potential must use, or their partners must use, a highly effective method of contraception (e.g., condom + spermicide, condom + diaphragm with spermicide, IUD) starting for at least one menstrual cycle prior to starting study drug and throughout the entire study period and for 30 days (longer if appropriate) after the last dose of study drug. Subjects with partners using hormonal contraceptives must also be using an additional approved method of contraception (as described previously). * Subjects willing and able to comply with the study protocol for the duration of the study and provide written informed consent prior to any study-specific screening procedures with the understanding that the subject may withdraw consent at any time without prejudice. Exclusion Criteria * Stage IV breast cancer. * Prior chemotherapy, radiation therapy, immunotherapy, or biotherapy for current breast cancer. * Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude any of the study therapy drugs. * Subjects with a concurrently active second malignancy other than adequately treated nonmelanoma skin cancers or in situ cervical cancer. * Subjects with known positive human immunodeficiency virus (HIV) status. * Pregnancy or breast feeding at the time of study enrollment. Eligible subjects of reproductive potential (both sexes) must agree to use adequate contraceptive methods during study therapy. * Subjects with known allergy or hypersensitivity to doxorubicin, cyclophosphamide, or eribulin mesylate. * Inability to comply with the study and/or follow-up procedures.

Study Objectives Aim of this non-interventional study is to investigate the tolerability of Effentora® in cancer pain patients with breakthrough pain under real-life conditions in clinical practice. Conditions: Cancer, Pain Intervention / Treatment: DRUG: Effentora® Location: Germany Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * decision to start treatment with Effentora * prescription in accordance with Summary of Product Characteristics (SmPC) * personally signed and dated Informed Consent document Exclusion Criteria: * any subject considered unsuitable according to SmPC

Study Objectives This study is designed to determine whether the combination of low dose cisplatin and strontium-89 shows clinical promise for the symptomatic treatment of bone metastases in hormone refractory prostate cancer. Conditions: Hormone Refractory Prostate Cancer, Bone Metastases Intervention / Treatment: DRUG: strontium-89, DRUG: cisplatin Location: Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * adenocarcinoma of the prostate * life expectancy > 3 months, * symptomatic from bone metastases * radiologic evidence of metastatic bone disease * stable level of pain control * >18 years * ability to complete assessments * prior treatment (chemo) > 4 weeks previous * discontinued anti-androgens for > 4 weeks Exclusion Criteria: * prior strontium therapy * previous hemibody RT within 6 weeks * previous cytotoxic chemotherapy within 4 weeks * use of bisphosphonate medications within 4 weeks * change in steroid dose within 4 weeks * active uncontrolled infection * impending or present spinal cord compression * significant neurological disorder * impending pathological fracture * severe urinary incontinence

Study Objectives This multicenter, randomized, double-blind study will estimate the efficacy, safety and tolerability of ipatasertib combined with paclitaxel compared with placebo combined with paclitaxel in participants with inoperable locally advanced or metastatic triple-negative breast cancer (mTNBC), as measured by progression-free survival (PFS) in all participants and in participants with phosphatase and tensin homolog (PTEN)-low tumors. Conditions: Breast Neoplasms Intervention / Treatment: DRUG: Ipatasertib, DRUG: Paclitaxel, DRUG: Placebo Location: Korea, Republic of, Italy, Spain, United States, Belgium, Singapore, Taiwan, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Histologically documented triple-negative adenocarcinoma of the breast that is inoperable locally advanced or metastatic and is not amenable to resection with curative intent * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen, required prior to randomization * Measurable disease, according to the RECIST v1.1 * Adequate hematologic and organ function within 14 days before the first study treatment * For female participants of childbearing potential, agreement (by both participant and partner) to use an effective form of contraception for the duration of the study and for 6 months after last dose of study treatment Exclusion Criteria: * Any previous therapy, including chemotherapy or hormonal or targeted therapy, for inoperable locally advanced or metastatic triple-negative adenocarcinoma of the breast. Participants may have received prior neoadjuvant or adjuvant chemotherapy and/or radiation treatment for locally advanced triple negative adenocarcinoma, provided all treatments were completed greater than or equal to (>=) 6 months prior to Cycle 1 Day 1. Locally recurrent disease must not be amenable to resection with curative intent * Any radiation treatment to metastatic site within 28 days of Cycle 1, Day 1 * Known Human Epidermal Growth Factor Receptor 2 (HER2) positive, erythrocyte receptor (ER) positive, or progesterone receptor (PR) positive breast cancer * Previous therapy with Akt, PI3K, and/or mTOR inhibitors * Major surgical procedure, open biopsy, or significant traumatic injury within 30 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study * Known presence of the brain or spinal cord metastasis, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening or prior radiographic assessments

Study Objectives A study to evaluate the safety, pharmacokinetics and anti-tumor activity of RO7300490 as a single agent or in combination with atezolizumab. The study will consist of 3 parts: \[Part 1\] Dose-Escalation of RO7300490 as a single agent; \[Part 2\] Dose-Escalation of RO7300490 in combination with atezolizumab and \[Part 3\] Dose-Expansion of RO7300490 in combination with atezolizumab in selected cancer types. Conditions: Solid Tumors Intervention / Treatment: DRUG: RO7300490, DRUG: Atezolizumab Location: Korea, Republic of, Spain, United Kingdom, Denmark, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: * Life expectancy of >= 12 weeks. * Histologically confirmed diagnosis of locally advanced and/or metastatic solid tumors that are not amenable to standard therapy. * Radiologically measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. * Agreement to provide protocol-specific biopsy material. * Adverse Events (AEs) from prior anti-cancer therapy resolved to Grade =<1. * Adequate performance status and cardiovascular, hematological, liver, renal and coagulation function. * For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse), use contraceptive measures and refrain from donating eggs. * For male participants: agreement to remain abstinent (refrain from heterosexual intercourse), use contraceptive measures and refrain from donating sperm. Exclusion Criteria: * Known central nervous system (CNS) primary tumors or metastases, including leptomeningeal metastases, unless protocol-specific conditions are met. * Active second invasive malignancy within two years prior to screening. * Significant cardiovascular/cerebrovascular disease within 6 months prior to study treatment start. * Any other diseases, metabolic dysfunction, physical examination finding or clinical laboratory finding that gives reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug. * Prior allogeneic bone marrow transplantation or prior solid organ transplantation. * Active or history of autoimmune disease. * Known hypersensitivity to any of the components of RO7300490 formulation or to components of atezolizumab formulation. * Pregnancy, lactation or breastfeeding. * Dementia or altered mental status that would prohibit informed consent. * Major surgery or significant traumatic injury within 28 days prior to the first study drug administration (excluding biopsies) or anticipation of the need for major surgery during study treatment. * Treatment with radiotherapy, chemotherapy, hormonal therapy, targeted therapy, immunotherapy or investigational drug concurrent or within 28 days or 5 half-lives of the drug (whichever is shorter) before the first study drug administration.

Study Objectives The study will evaluate the safety and efficacy of Patupilone in adult patients with advanced solid tumors. Conditions: Tumors Intervention / Treatment: DRUG: Patupilone Location: Japan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion criteria: * Patients with a histologically/cytologically confirmed diagnosis of advanced solid tumors refractory to or unsuitable for standard therapy, or for whom no standard therapy exists * Patients with WHO Performance Status of 0-1 ( Karnofsky Performance Status of 80-100) * At least one measurable lesion Exclusion criteria: * Patients with any peripheral neuropathy * Patients with unresolved diarrhea * Patients with severe and/or uncontrolled medical conditions or infections that require systemic therapy Other protocol-defined inclusion/exclusion criteria may apply

Study Objectives The objective is to compare efficacy and safety of AB1010 at 3 or 6 mg/kg/day in treatment of patients with mastocytosis with handicap and bearing activating point mutations in the phosphotransferase domain of c-Kit such as the main mutation Asp-816-Val (D816V). Conditions: Mastocytosis Intervention / Treatment: DRUG: masitinib Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patients with one of the following documented mastocytosis: * Smouldering systemic mastocytosis * Indolent systemic mastocytosis with organomegaly * Indolent Systemic Mastocytosis having 2 infiltrated organs (skin and bone-marrow) * Any mastocytosis with in the last 6 months at least 3 anaphylactic shocks or syncops requiring either use of adrenaline or medical assistance * Cutaneous Mastocytosis (CM) * Skin biopsy-documented mastocytosis and evaluable disease based upon: * Histological criteria: typical infiltrates of mast cells in a multifocal or diffuse pattern in skin biopsy * Clinical criteria: typical skin lesions (maculopapular, urticaria pigmentosa, mastocytoma) * Missing data (c-kit molecular analysis not done) or documented presence of an activating point mutation in the phosphotransferase domain of c-kit such as D816V c-kit mutation in at least one infiltrated organ (bone marrow or skin) * Refractory to at least one of the symptomatic treatments such as: * Anti H1 * Anti H2 * Proton pump inhibitor * Osteoclast inhibitor * Cromoglycate Sodium * Antileukotriene * Other therapies used for the symptomatic care * Handicap defined as at least one of the following handicaps: * pruritus score >= 6 * number of flushes per week >= 7 * number of stools per day >= 4 , * number of mictions per day >= 8 , * QLQ-C30 score >= 60, * Hamilton score >= 10 Exclusion Criteria: * Patients with one of the following mastocytosis: * Systemic Mastocytosis with an Associated clonal Hematologic Non Mast cell lineage Disease (SM-AHNMD) * Mast cell leukemia (MCL) * Aggressive systemic mastocytosis (ASM) * Patient with a major surgery within 2 weeks prior to study entry * No vulnerable population will be included in this study * Life expectancy < 6 months. * Patient is < 5 years free of malignancy, except treated basal cell skin cancer or cervical carcinoma in situ. * Patient with grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study) * Patient has a severe and/or uncontrolled medical disease. * Patient has a known diagnosis of human immunodeficiency virus (HIV) infection

Study Objectives The purpose of this multicenter,open, prospective and single arm study is to evaluate the efficacy and safety of domestic dasatinib in the first-line treatment of newly diagnosed CML-CP. Conditions: Chronic Myelogenous Leukemia - Chronic Phase Intervention / Treatment: DRUG: Dasatinib Tablets Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Aged >= 18 years and gender is not limited. * The chronic-phased CML subjects with Ph + were definitely diagnosed within 6 months before the first use of the study drug. The diagnostic criteria refer to the 2016 edition of Chinese CML diagnosis and treatment guidelines. * The Eastern Cooperative Oncology Group (ECOG) performance of 0-2. * The function of main organs such as liver and kidney is normal, which shows that serum bilirubin is less than or equal to 1.5 × ULN； Serum ALT and AST <= 2.5 × ULN； Serum Cr <= 1.5 × ULN； Serum amylase and lipase <= 1.5 × ULN; Blood potassium, magnesium, phosphorus and total calcium were more than or equal to the lower limit of normal value, or were corrected to normal range before administration. * The subjects voluntarily participate in and signed the informed consent form (ICF), and the process of signing the ICF meet the requirements of the "Practice for quality management of drug clinical trials". Exclusion Criteria: * Subjects who have received any TKI treatment in the past. * Subjects who have received or are receiving anti CML chemotherapy drugs (except hydroxyurea). * Subjects who have received major surgery or no recovery from previous surgery within 4 weeks (including 4 weeks) before the first use of the study drug. * Subjects with mental illness, including epilepsy, dementia, severe depression, mania, etc. * Subjects with a history of significant congenital or acquired hemorrhagic disease unrelated to CML. * Disease history and comorbidities: a) uncontrolled severe disease or active infection that impairs the subject's ability to receive the treatment; b) Uncontrolled or major cardiovascular disease; c) Pulmonary hypertension; d) Subjects with pleural effusion or pericardial effusion of any grade are excluded when screening; when entering the study, subjects with remission of pleural / pericardial effusion of any grade previously diagnosed were allowed to participate in the study. * Subjects with gastrointestinal dysfunction or gastrointestinal diseases that may significantly affect the absorption of the test drug, such as ulcers, uncontrollable nausea, vomiting, diarrhea, malabsorption syndrome, after a small bowel resection, etc. * Cardiac dysfunction, including: a) complete left bundle branch block; b) Long QT syndrome, or known family history of long QT syndrome; c) Ventricular or atrial tachyarrhythmia of clinical significance; d) Clinically significant resting bradycardia (< 50 beats per minute); e) QTc>450msec； f) History of clinically confirmed myocardial infarction in the past 12 months; g) History of unstable angina in the past 12 months; h) Other clinicallysignificant heart diseases (e.g., congestive heart failure, etc.). * Combined with other primary malignant tumors (except basal cell carcinoma of skin). * Subjects who are receiving treatment with strong CYP3A4 inhibitors (e.g., erythromycin Ethylsuccinate, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, imipradil, etc.) and cannot discontinue or switch to other drugs before starting the study drug. * Subjects who are receiving strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine, phenobarbital, Hypericum perforatum, etc.) and the treatment cannot be stopped or replaced by other drugs before starting the study drug. * Subjectswho are receiving the treatment of drugs that may prolong QT interval, and the treatment can not be stopped or replaced by other drugs before starting to use the study drug. * Previous history of acute (within 1 year before inclusion) or chronic pancreatitis. * Known or suspected to be allergic to this kind of drug. * Female and male subjects of childbearing age who cannot use adequate methods of contraception , including pregnant or lactating women. * Subjects who are receiving the treatment of other test drugs or participated in the clinical trial of other drugs within one month. -

Study Objectives This phase I trial studies the best dose and side effects of trigriluzole in combination with nivolumab and pembrolizumab in treating patients with solid malignancies or lymphoma that has spread to other places in the body or cannot be removed by surgery. Trigriluzole may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as nivolumab and pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving trigriluzole in combination with nivolumab and pembrolizumab may work better at treating patients with solid malignancies or lymphoma. Conditions: Lymphoma, Metastatic Malignant Solid Neoplasm, Metastatic Melanoma, Metastatic Renal Cell Cancer, Recurrent Bladder Carcinoma, Recurrent Classical Hodgkin Lymphoma, Recurrent Head and Neck Squamous Cell Carcinoma, Recurrent Lymphoma, Recurrent Malignant Solid Neoplasm, Recurrent Renal Cell Carcinoma, Stage III Bladder Cancer, Stage III Lymphoma, Stage III Non-Small Cell Lung Cancer AJCC v7, Stage III Renal Cell Cancer, Stage III Skin Melanoma, Stage IIIA Non-Small Cell Lung Cancer AJCC v7, Stage IIIA Skin Melanoma, Stage IIIB Non-Small Cell Lung Cancer AJCC v7, Stage IIIB Skin Melanoma, Stage IIIC Skin Melanoma, Stage IV Bladder Cancer, Stage IV Lymphoma, Stage IV Non-Small Cell Lung Cancer AJCC v7, Stage IV Renal Cell Cancer, Stage IV Skin Melanoma, Stage IVA Bladder Cancer, Stage IVB Bladder Cancer, Unresectable Head and Neck Squamous Cell Carcinoma, Unresectable Solid Neoplasm Intervention / Treatment: DRUG: Enzyme Inhibitor Therapy, OTHER: Laboratory Biomarker Analysis, BIOLOGICAL: Nivolumab, BIOLOGICAL: Pembrolizumab 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 histologically confirmed solid malignancy or lymphoma that is metastatic or unresectable * There is reasonable expectation of response to pembrolizumab or nivolumab, and one of the drugs is available from the commercial supply; this includes (but is not limited to) the following tumor types: melanoma, non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, bladder cancer, and classic Hodgkin lymphoma * The patient must have failed at least one line of standard treatment, with the following exceptions in which a PD-1 antibody is Food and Drug Administration (FDA) approved in the first-line setting: * Melanoma patients * Non-small cell lung cancer patients without EGFR or ALK genomic tumor aberrations whose tumors have high PD-L1 expression (tumor proportion score [TPS] >= 50%) as determined by an FDA-approved test * Patients must give informed consent * Prior chemotherapy, immunotherapy, radiotherapy or major surgery (including radiation therapy or surgery for treatment of brain metastases) must be completed at least 3 weeks before study entry; prior PD-1 or PD-L1 therapy is acceptable * Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2 * Hemoglobin > 8.0 mg/dL (without transfusion in the preceding 7 days) * Platelets >= 70,000 /uL * Total bilirubin within normal institutional limits (patients with Gilbert's syndrome must have a total bilirubin < 3.0 mg/dL) * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 2 X institutional upper limit of normal (ULN) * Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2 X institutional ULN * Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm by computed tomography (CT) scan, positron emission tomography (PET)/CT scan, magnetic resonance imaging (MRI) or caliper/ruler measurement by clinical exam; lymph nodes: to be considered pathologically enlarged and measurable, a lymph node must be >= 15 mm in short axis when assessed by CT scan; lesions that have been radiated in the advanced setting cannot be included as sites of measurable disease unless clear tumor progression has been documented in these lesions since the end of radiation therapy * Ability to swallow pills Exclusion Criteria: * Systemic immunosuppressive medications such as steroids; the following steroid formulations are permitted: intranasal, intra-articular, and inhaled steroids * History of immune-related adverse event from prior immunotherapy treatment that has not improved to grade 0-1; subjects with grade 2 hypothyroidism and grade 2 adrenal insufficiency requiring continued medical treatment may enroll provided that they are asymptomatic and stable on their dose of hormone replacement * Serious concomitant systemic disorders (including active infections) that would compromise the safety of the patient or compromise the patient?s ability to complete the study, at the discretion of the investigator, including active autoimmune disease requiring treatment within the past 30 days * Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other systemic immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption)' physiologic replacement doses of systemic corticosteroids are permitted, even if < 10 mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted * Second primary malignancy, except those second primary malignancies that are not considered to be competing causes of death in the opinion of the treating investigator; examples include: in situ carcinoma of the cervix, adequately treated non-melanoma carcinoma of the skin, or other malignancy treated at least 5 years previously with no evidence of recurrence * Patients with active, untreated central nervous system (CNS) metastases will be excluded from this clinical trial; patients who have brain metastases that been treated with radiation therapy or surgery will be required to have a washout period of at least 3 weeks prior to study entry, must be neurologically asymptomatic, and must not require systemic steroids * Women of child-bearing potential and men must agree to use adequate contraception prior to the start of treatment, for the duration of treatment, and for 5 months after last dose of study treatment * Patients with immune deficiency have impaired immune responses, therefore, known human immunodeficiency virus (HIV)-positive patients are excluded from the study

Study Objectives The purpose of this research study is to find out what effects, good and/or bad, erlotinib has on the patient and their myelodysplastic syndrome. Erlotinib has been approved by the Food and Drug Administration (FDA) to treat non-small cell lung cancer; however, erlotinib use in this study is considered investigational as the FDA has not approved it for the treatment of myelodysplastic syndrome. Conditions: Myelodysplastic Syndrome Intervention / Treatment: DRUG: Erlotinib 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 an established diagnosis of myelodysplastic syndrome (MDS) and have either: Low or intermediate 1 risk disease by International Prognostic Scoring System (IPSS) for MDS with symptomatic anemia (defined as hemoglobin less than 10.0 g/dl) or transfusion dependent anemia (defined as requiring >= 4 units of red blood cells (RBCs) administered with a pretreatment hemoglobin value of <= 9 g/dL in the 8 weeks prior to Day 1 of treatment in this study). Patients with anemia must have no response to at least to 6 weeks trial of erythroid stimulating agents (ESA) [erythropoietin/ darbepoetin]. Patients with serum erythropoietin levels more than 500 mU/ ml on diagnosis are eligible to the study without erythropoietin/darbepoetin prior treatment. Patients who do not meet anemia criteria are still eligible if they had thrombocytopenia with two or more platelet counts < 50 x 10^9/L or a significant clinical hemorrhage requiring platelet transfusions or if they had neutropenia with an absolute neutrophil count (ANC) < 1 x 10^9/L; Intermediate-2 or high risk MDS by IPSS. * Patients >= 60 years with Acute Myeloid Leukemia (AML) by WHO classification and myeloblasts percentage 20-30% (RAEB-t by MDS French-American-British (FAB) classification) are eligible for the study if deemed not suitable for induction chemotherapy or declined that option. * All prior treatment must have been discontinued 28 days prior to Day 1 of treatment in this study except (ESA) and colony stimulating factors where it should be stopped 14 days prior to start therapy on study, and hydroxyurea should be stopped 2 days before. * Prior bone marrow or stem cell transplant is allowed. * Secondary or therapy related MDS patients are eligible. * Patients with chronic myelomonocytic leukemia (CMML) are eligible. * Patients must have a performance status of 0 - 2 by Zubrod performance status criteria. * Pretreatment pathology materials must be available for morphologic review. Collection of blood and marrow specimens for pathology review must be completed within 28 days prior to registration. * No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for at least 2 years. * In calculating days of tests and measurements, the day a test or measurement is done is considered Day 0. Therefore, if a test is done on a Monday, the Monday four weeks later would be considered Day 28. This allows for efficient patient scheduling without exceeding the guidelines. If Day 28 or 60 falls on a weekend or holiday, the limit may be extended to the next working day. * All patients must be informed of the investigational nature of this study and must sign and give written consent in accordance with institutional and federal guidelines. Exclusion Criteria: * Patients must not have received prior remission induction chemotherapy as treatment for MDS. * Patients must not be pregnant or nursing because of the potential risks of the drugs used in this study. Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. * Patients who are known HIV positive are not eligible for this study.

Study Objectives This is a Phase I study combining vemurafenib and hydroxychloroquine in the treatment of BRAF V600E+ metastatic melanoma. Conditions: Melanoma Intervention / Treatment: DRUG: Hydroxychloroquine (HCQ), DRUG: Vemurafenib (VEM) Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: SINGLE

Inclusion Criteria: * Patients must be at least 18 years of age. * Patients must have histologically confirmed diagnosis of Stege IV metastic melanoma positive for BRAF V600E mutation by either the COBAS test or other CLIA approved assay. * Patients must have a ECOG performance status of 0 or 1. * Patients must have the following hematologic, renal and liver function: absolute neutrophil count > 1500/mm3, platelets > 100,000/mm3, hemoglobin >9g/dL, creatinine <= 2 times the upper limits of normal (ULN), albumin > 2g/dL, total bilirubin <= 1.5 mg/dl, ALT and AST <= 3 times above the upper limits of the institutional norm. * Patients must be able to provide written informed consent. * Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women. Women of non-childbearing potential may be included without serum pregnancy test if they are either sugically sterile or have been postmenopausal for >= 1 year. Fertile men and women must an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician. Effective methods of contraception are defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistenly and correctly (for example implants, injectables, combined oral contraception or intra-uterine devices). At the discretion of the Investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. (Periodic abstinence (e.g. calendar, ovulation, sympothermal, postovulation methods) with withdrawal are not acceptable methods of contraception.) * Patients with treated brain metastases that have been stable for 1 month are eligible; patients must be off steroids for 1 week prior to starting study treatment. * Any number and type of prior anticancer therapies except BRAF or MEK inhibitors. * Patients must have discontinued active immunotherapy (IL-2, interferon, CTLA-4, etc.) or chemotherapy at least 4 weeks prior to entering the study and oral targeted therapy at least 2 weeks prior to entering the study and have recovered from adverse events due to those agents. Patients must not receive any other investigational anticancer therapy during the period on study or the four weeks prior to entry, with the exception of vaccines. Exclusion Criteria: * Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety. * Patients who are pregnant and breast-feeding. * Patients receiving concurrent therapy for their tumor (i.e.chemotherapeutics or investigational agents). * Patients with leptomeningeal disease. * Patients with a concurrent or prior malignancy within the last 2 years, unless they are patients with curatively treated carcinoma-in-situ, or basal cell carcinoma or squamous cell carcinoma of the skin. Patients with treated prostate cancer or breast cancer for which no concurrent therapy is indicated are eligible for this study. Patients who have been free of disease (any prior malignancy) for >= five years are eligible for this study. * Due to risk of disease exacerbation patients with porphyria are not eligible. * Due to risk of disease exacerbation patients with psoriasis are ineligible unless the disease is well controlled and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations. * Patients receiving cytochrome P450 enzyme-inducing anticonvulsant drugs (EIADs) (i.e. phenytoin, carbamazepine, Phenobarbital, primidone, or oxcarbazepine) are ineligible. * Patients with previously documented macular degeneration or diabetic retinopathy are ineligible. * Patients with prior exposure to BRAF or MEK inhibitors are not eligible. * Because patients witn immune deficiency are at increased risk of lethal infections when treated with bone marrow-suppressive therapy, HIV-positive patients are excluded from the study. For patients receiving combination anti-retroviral therapy, the potential impact of pharmacokinetic interactions with HCQ and VEM is unknown. Appropriate studies may be undertaken in patients with HIV and those receiving combination anti-retrovital therapy in the future. * History of congenital long QT syndrome or a corrected QTc interval >= 450 msec at baseline.

Study Objectives Primary Objective: * To determine the maximum tolerated dose (MTD) of Dasatinib in relapsed or refractory non-hodgkin's lymphoma (NHL) patients and to determine the safety of Dasatinib in NHL. Secondary Objectives: * To assess the complete and overall response rates for all Phase I and Phase II patients and to determine overall survival and event free survival for all Phase I and Phase II patients. * To assay the levels of kinase activity in NHL specimens and correlate this activity to patient outcomes. Conditions: Non-Hodgkin's Lymphoma Intervention / Treatment: DRUG: Dasatinib, DRUG: Dasatinib Maximum Tolerated Dose Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically confirmed diagnosis of non-hodgkin's lymphoma that is recurrent or refractory after at least one prior therapy and for which no other potentially curative therapy is available. * Subject, age > or = 19 years * Performance status (ECOG) 0-2 * Patients must have relapsed or refractory disease after at least one prior systemic therapy, with at least a 3 week interval from the completion of the most recent chemotherapy or radiotherapy regimen. Recover to <= grade 1 from all toxicities related to the prior treatments is required. * Patients must be ineligible or relapsed after an autologous or allogeneic stem cell transplant if clinically appropriate. * Adequate Laboratory Parameters: * ANC >= 1000/μL * Platelet count >= 50,000/μL * Total bilirubin < 2.0 times the institutional upper limit of normal (ULN) * Hepatic enzymes (AST, ALT ) <= 2.5 times the institutional ULN * Serum creatinine < 2.0 times the institutional ULN * PTT within institutional normal limits * Ability to take oral medication (dasatinib must be swallowed whole) * Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (sensitivity < or = 25IU HCG/L) within 72 hours prior to the start of study drug administration * Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 6 months after study drug is stopped * Signed written informed consent including HIPAA according to institutional guidelines Exclusion Criteria: * No malignancy [other than the one treated in this study] which required systemic treatment within the past 3 years. * Concurrent medical condition which may increase the risk of toxicity, including: * Clinically significant pleural or pericardial effusion * Clinically-significant coagulation or platelet function disorder (e.g. known von Willebrand's disease) * Cardiac Symptoms, consider the following: * Uncontrolled angina, congestive heart failure or MI within (6 months) * Diagnosed congenital long QT syndrome * Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) * Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec) * Subjects with hypokalemia or hypomagnesemia if it cannot be corrected * History of significant bleeding disorder unrelated to cancer, including: * Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease) * Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) * Ongoing or recent (< or = 3 months) significant gastrointestinal bleeding * Concomitant Medications, consider the following prohibitions: * Drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Patients must discontinue drug 7 days prior to starting dasatinib.) quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide,erythromycin, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine. * The concomitant use of H2 blockers or proton pump inhibitors with dasatinib is not recommended. The use of antacids should be considered in place of H2 blockers or proton pump inhibitors in patients receiving dasatinib therapy. * Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy * Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia. * Patient may not be receiving any prohibited CYP3A4 inhibitors * Women: * Are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks 6 months after cessation of study drug * Have a positive pregnancy test at baseline * Are pregnant or breastfeeding * Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness

Study Objectives This was a monocentric, open label, non-randomised, non-comparative, dose-finding phase I study Conditions: Advanced Solid Tumors Intervention / Treatment: DRUG: Lucitanib Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Chinese male or female patient aged >= 18 years old and <= 70 years old. * Estimated life expectancy >= 12 weeks. * Histologically or cytologically confirmed, locally advanced or metastatic solid tumor, refractory to standard therapy or no standard therapy available. * Full recovery (to grade <= 1) from any prior surgical procedure(s) and from reversible side effects of prior therapy for cancer including radiation therapy, chemotherapy, small molecule therapeutics and immunotherapy. * Patients should be evaluable according to RECIST criteria, version 1.1. * Adequate haematological, hepatic and renal functions: Absolute neutrophil count (ANC) >= 1.5x 10^9/L Platelet counts >= 100 x 10^9/L. Haemoglobin >= 9 g/dL. Creatinine clearance > 50 mL/min (assessed with MDRD formula). Proteinuria qualitative test < 1+. If proteinuria qualitative test >= 1+, proteinuria over 24 hours should be < 1.0 g/24hrs. INR <= 1.5. AST, ALT <= 1.5 x Upper Limit of Normal Value (ULN) (<= 3 x ULN in case of liver metastasis). Bilirubin < 1.5 x ULN. * Eastern Co-operative Group (ECOG) performance status <= 1. * Ability to swallow oral capsules. * Negative serum pregnancy test at screening in women of childbearing potential within 7 days prior the study drug intake. * Willingness and ability to comply with study procedures. * Signed written Informed Consent Form. Exclusion Criteria: * Participation in another therapeutic clinical trial at the same time or within 4 weeks prior to first AL3810 intake. In case of involvement in a non-interventional clinical trial (e.g. epidemiological study), inclusion in the present study is possible. * Foreseeable poor compliance to the study procedures. * Known active central nervous system (CNS) metastases not controlled by prior surgery or radiotherapy and/or low dose steroids. * Active second malignancy or history of other malignancy within 2 years, with the exception of non-melanoma skin cancers or carcinoma in situ (CIS) of the breast or cervix or controlled, superficial carcinoma of the bladder. * Chemotherapy including biologic/targeted therapy or immunological agents within 4 weeks or 5 half-lives of the agent, whichever the longest, before inclusion. * Previous treatment with bevacizumab within 3 months before the first day of AL3810 administration. * Patients who received radiotherapy within 4 weeks of starting study treatment. * Major surgery within 4 weeks before first day of study drug administration. * History of clinically significant or uncontrolled cardiac disease, including congestive heart failure (New York Heart Association functional classification >= 3), angina, myocardial infarction or ventricular arrhythmia. * Significant cardiovascular disease or condition, including: Congestive heart failure requiring therapy. Ventricular and/or supra-ventricular arrhythmia requiring therapy. Severe conduction disturbance (including QTc interval prolongation > 450 msec [corrected], history of severe arrhythmia, or history of familial arrhythmia [e.g., Wolff-Parkinson-White syndrome]). Angina pectoris requiring therapy. Left ventricular ejection fraction (LVEF) < 50% evaluated by cardiac ultrasound (ECHO) or Multi Gated Acquisition Scan (MUGA). Myocardial infarction (MI) within 6 months prior to administration of the first dose. Cardiovascular disease > Class I, according to the New York Heart Association's (NYHA) Functional Criteria. Uncontrolled arterial hypertension (defined as systolic blood pressure >= 140mmHg and/or diastolic blood pressure >= 90mmHg with optimized antihypertensive therapy or patients treated with >=2 antihypertensive agents) or systolic blood pressure >= 160mmHg and/or diastolic blood pressure >= 100mmHg with or without antihypertensive therapy. * Patients with thromboembolic events < 12 months prior to treatment start or at high risk of such events. * Ongoing treatment with warfarin or other oral anticoagulant. * Unavoidable concomitant treatment with any drug known for potential risk of causing Torsades de Pointes. * Serum potassium (K+) levels below LLN or 3.0 mmol/L at screening. * Patients who received administration of strong inhibitors of CYP2C8 and/or CYP3A4 or strong inducers of CYP3A4 within 7 days before the first dose of AL3810 or have on-going requirements for these medications (appendix 15). * Significant gastrointestinal abnormalities, including ulcerative colitis, chronic diarrhoea associated with intestinal malabsorption, Crohn's disease, or decided by investigator. * Known pre-existing clinically significant disorder of the hypothalamic-pituitary axis, thyroid and adrenal gland. * Serious/active bacterial, viral or fungal infection (including known active human immunodeficiency virus [HIV] infection) requiring systemic treatment. * Concomitant uncontrolled severe systemic disease (e.g., uncontrolled diabetes mellitus, etc.). * Psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary study procedures. * Known organ dysfunction which would either compromise the patient's safety or interfere with the evaluation of AL3810. * Men and women of child bearing potential unable or unwilling to employ effective contraception (abstinence, barrier method with spermicide, intrauterine device, or steroidal contraceptive for women and barrier method) during the study and for 6 months thereafter.

Study Objectives The purpose of this study is to determine the tolerability of ME-143, find the maximum tolerated dose, and the safety profile in patients with refractory solid tumors. Conditions: Solid Tumors Intervention / Treatment: DRUG: ME-143 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: * Provision of informed consent * Male or female >=18 years of age * Histologic or cytologic confirmed locally advanced or metastatic cancer that has no standard therapeutic alternatives. * ECOG Performance status 0-1 * A minimum life expectancy of 12 weeks * Adequate bone marrow, hepatic and renal function as evidenced by * Absolute neutrophil count (ANC) > 1.5 x 109/L * Platelet count > 100 x 109/L * Hemoglobin > 9.0 g/dL * Serum bilirubin < 1.5 x ULN * AST/ALT (SGOT/SGPT) < or = 2.5 x ULN for the reference laboratory or < 5 x ULN in the presence of liver metastases * Serum creatinine < or = 1.5 x ULN * Follicle-Stimulating Hormone (FSH) within normal baseline levels * Male patients should have a detectable level of testosterone * Female patients who are known to be capable of conception should have a negative serum pregnancy test (beta-human chorionic gonadotropin β-hCG]) within 1 week of starting the study. * All potentially fertile patients will agree to use an effective form of contraception during the study and for 90 days following the last dose of ME-143 (an effective form of contraception is defined as an oral contraceptive or a double barrier method). * At least 4 weeks must have elapsed prior to Day 1 Cycle 1 since prior chemotherapy (6 weeks for carmustine or mitomycin C), investigational drug or biologic therapy and any toxicity associated with these treatments has recovered to <= NCI-CTCAE Grade 1. * At least 21 days must have elapsed prior to Day 1 Cycle 1, radiotherapy (limited palliative radiation is allowed > 2 weeks), immunotherapy or following major surgery and any surgical incision should be completely healed Exclusion Criteria: * Patients who are pregnant or breastfeeding * Tumor involvement of the Central Nervous System (CNS) Patients with treated and stable CNS metastases may be eligible to participate after discussion and approval from the Medical Monitor * Uncontrolled infection or systemic disease. * Clinically significant cardiac disease not well controlled with medication (e.g., congestive heart failure, symptomatic coronary artery disease e.g. angina, and cardiac arrhythmias) or myocardial infarction within the last 12 months. * Patients with QTc of > 470 msec on screening ECG. (If a patient has QTc interval >470 msec on screening ECG, the screening ECG may be repeated twice (at least 24 hours apart). The average QTc from the 3 screening ECGs must be <470 msec in order for the patient to be eligible for the study. * Any major surgery, radiotherapy, or immunotherapy within the last 21 days (limited palliative radiation is allowed > 2 weeks). * Chemotherapy regimens with delayed toxicity within the last 4 weeks (or within 6 weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens given continuously or on a weekly basis with limited potential or delayed toxicity within the last 2 weeks. * No concurrent systemic chemotherapy or biologic therapy is allowed. * Known hypersensitivity to any components of ME-143 study drug product. * Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both). * History of solid organ transplantation. * Psychiatric disorder or social or geographic situation that would preclude study participation.

Study Objectives The purpose of this study is to compare icotinib with induction and maintenance chemotherapy in the first-line treatment of advanced non-small cell lung cancer (NSCLC) patients with EGFR mutation. Conditions: NSCLC Intervention / Treatment: DRUG: Icotinib, DRUG: Chemotherapy Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Recurrent or progressive Non-Small Cell Lung Cancer stage IV or IIIB patients. * Positive EGFR Mutation. * No previous systemic anticancer therapy. * Measurable lesion according to RECIST with at least one measurable lesion not previously irradiated, unless disease progression has been documented at that site. * Provision of written informed consent. Exclusion Criteria: * Experience of Anti-EGFR(the epidermal growth factor receptor) Monoclonal Antibody or small molecular compounds therapy such as gefitinib, erlotinib or Cetuximab. * Evidence of clinically active Interstitial Lung Diseases (Patients with chronic, stable, radiographic changes who are asymptomatic need not be excluded). * Known severe hypersensitivity to icotinib or any of the excipients of this product. * Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the study.

Study Objectives Defects in the apoptotic process can lead to the onset of cancer by allowing cells to grow unchecked when an oncogneic signal is present. Obatoclax is designed to restore apoptosis through inhibition of the Bcl-2 family of proteins, thereby reinstating the natural process of cell death that is often inhibited in cancer cells. This is a multi-center, open-label, Phase I/II study of obatoclax administered in combination with docetaxel in 3-week cycles to patients with relapsed or refractory Non-Small Cell Lung Cancer. Treatment may be administered on an outpatient basis. No investigation or commercial agents or therapies other than those described herein may be administered with the intent to treat the patient's malignancy. Supportive care measures including those directed at controlling symptoms resulting from Non-Small Cell Lung Cancer are allowed. Conditions: Lung Cancer Intervention / Treatment: DRUG: Obatoclax mesylate 250 ml, DRUG: Docetaxel 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: * Pathological confirmation of Non-Small Cell Lung Cancer (NSCLC) * Must have been previously treated with a single platinum-based chemotherapy regimen and shown evidence of disease progression; no further limitations * Must have normal organ function * Must be willing to submit to blood sampling for planned PK and PD analysis * Must have the ability to understand and willingness to sign a written informed consent form Exclusion Criteria: * No other agents or therapies administered with the intent to treat malignancy * Patients with prior exposure to obatoclax or docetaxel * Uncontrolled, intercurrent illness * Pregnant women and women who are breast feeding

Study Objectives First randomization: After inclusion Use of Daunorubicin (arm D) or Idarubicin (arm I) as anthracyclin during all courses of chemotherapy (induction, consolidation courses before ASCT) Second randomization: After achieving 1st CR: all patients received non intensive consolidation course Familial HLA typing required for all patients Patients with HLA-identical sibling: Patients with very good prognostic factors (CBF leukemias, WBC \< 30 giga/l at diagnosis, 1st CR after one induction course) = arm C: no allogeneic stem cell transplantation in 1st CR; received 2 more courses of intensive consolidation chemotherapy All others patients received an allogeneic transplant For patients aged less than 51 = arm M: upfront myeloablative conditioning regimen For patients aged over 51 and less than 61= arm m: intensive chemotherapy consolidation course. Conditions: Acute Myeloid Leukemia Intervention / Treatment: DRUG: Zavedos, DRUG: Cerubidine Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2, PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patients aged 15 to 60 years * Diagnosis untreated AML (FAB 0 to 2, 4 to 7): more than 20% marrow blasts according to WHO classification * Signed informed consent required Exclusion Criteria: * AML3 subtype * Previous diagnosis of myelodysplastic syndrome (MDS) or myeloproliferative disease; patients with previous chemotherapy or radiotherapy were eligible if they had no previous diagnosis of MDS * Isolated extramedullary disease * Inadequate performance status (>= 3), cardiac function (LVEF < 40%, severe arythmia or unstable coronary disease), renal function (creatininine > 150 µmol/l), liver functional tests (bilirubin > 35 µmol/l, liver enzymes > 4 times normal values); life expectancy < 3 months * Informed consent refusal

Study Objectives Patient will receive either one infusion of rituximab IV and seven administrations of rituximab SC (experimental arm) or four infusions of rituximab IV (standard arm). The hypothesis is that the use of rituximab by sub cutaneous route and the scheme of administration could: * optimize rituximab exposure leading to improve response rate * increase adaptative response and then improve long-term control disease. Conditions: Follicular Lymphoma Intervention / Treatment: DRUG: Rituximab IV, DRUG: Rituximab SC Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically confirmed follicular lymphoma CD20+ grade 1, 2 and 3a by biopsy within 4 months before signing informed consent * Have a bone marrow biopsy within 4 months before the first study drug administration * Have no prior therapy except surgery for diagnosis * Aged 18 years or more with no upper age limit * ECOG performance status 0-2 * Ann Arbor Stage II, III or IV * Bi-dimensionally measurable disease defined by at least one single node or tumor lesion > 1.5 cm assessed by CT scan and/or clinical examination * With low-tumor burden defined as: * Nodal or extra-nodal tumor mass with diameter less than 7 cm in its greater diameter * And involvement of less than 3 nodal or extra nodal sites with diameter greater than 3 cm * And absence of B symptoms * And no symptomatic splenomegaly * And no compression syndrome (ureteral, orbital, gastrointestinal...) * And no pleural or peritoneal serous effusion * And no cytopenia, with hemoglobin > 10 g/dL (6.25mmol/L) and absolute neutrophil count> 1.5 G/L and platelets > 100 G/L within 28 days before the randomization * And LDH < ULN within 28 days before the randomization * And β2 microglobulin < ULN within 28 days before the randomization * Have signed an informed consent * Must be covered by a social security system Exclusion Criteria: * Grade 3b follicular lymphoma * Ann Arbor Stage I * Seropositive for or active viral infection with hepatitis B virus (HBV) HBs Ag positive HBs Ag negative, anti-HBs antibody positive and/or anti-HBc antibody positive and detectable viral DNA Note: Patients who are HBs Ag negative, anti-HBs positive and/or anti-HBc positive but viral DNA negative are eligible Patients who are seropositive due to a history of hepatitis B vaccine are eligible * Known seropositive for, or active viral infection with hepatitis C virus (HCV) * Known seropositive for, or active viral infection with Human Immunodeficiency Virus (HIV) * Any of the following laboratory abnormalities within 28 days before the randomization: Total bilirubin or GGT or AST or ALT > 3 ULN. Calculated creatinine clearance (Cockcroft and Gault formula) < 60 mL /min * Presence or history of CNS involvement by lymphoma * Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for >= 3 years * Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. * Patient with mental deficiency preventing proper understanding of the informed consent and the requirements of treatment. * Adult under law-control * Adult under tutelage * Contraindication to use rituximab or known sensitivity or allergy to murine products * Pregnant or lactating females. * Concomitant disease requiring prolonged use of corticosteroids or corticosteroids administration for lymphoma within 28 days before the first study drug administration. * Male and female patients of childbearing potential who cannot or do not wish to use an effective method of contraception, during the study treatment and for 12 months thereafter.

Study Objectives The primary objective is to assess antitumor activity of the combination of bevacizumab, pemetrexed and carboplatin, in terms of time to progression. Conditions: Mesothelioma Intervention / Treatment: DRUG: Bevacizumab, Pemetrexed, Carboplatin Location: Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically proven malignant pleural mesothelioma, inoperable, non previously treated with chemotherapy including intracavitary administration * PS 0-1 * Measurable and/or evaluable lesions according to RECIST criteria * Adequate organ function Exclusion Criteria: * Uncontrolled hypertension * Evidence of bleeding diathesis or coagulopathy * Pregnancy or breast-feeding

Study Objectives This is a randomized, double-blind, multicenter clinical phase III study involving about 105 cancer patients aged \>18 years who are receiving palliative chemotherapy and who are suffering from chemotherapy associated anemia. A standard treatment group (ERYPO®) will be included to provide a reference reflecting current standard medical practice. Conditions: Anemia Intervention / Treatment: DRUG: HX575, solution for injection (s.c.), DRUG: ERYPO®, Janssen-Cilag, solution for injection (s.c.) Location: Romania, Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Patients with a confirmed diagnosis of solid tumors * Patients who receive cyclic palliative chemotherapy with a cycle duration of 1 -4 weeks (for at least 12 weeks) during the study * Patients with chemotherapy associated anemia (hemoglobin < 10.0 g/dl at screening) * Life expectancy of at least 6 months Age: > 18 * Eastern Cooperative Oncology Group performance status of 0, 1 or 2 * Serum ferritin greater or equal to 100 µg/l and/or saturated transferrin levels greater or equal to 20 % * Adequate renal function (serum creatinine below or equal to 2.0 mg/dl) * Adequate hepatic function (bilirubin < 1.5 times upper limit of normal range * Patients with ability to follow study instructions, likely to complete all required visits and able to perform the quality of life assessment * Written informed consent of the patient Exclusion Criteria: * Patients who receive curative intended chemotherapy * Known primary or metastatic malignancy of the central nervous system * Known primary or metastatic malignancy of bone marrow * Primary hematologic disorder (e.g. myelodysplastic syndrome, sickle cell anemia, hematological malignancy, acute leukemia) * Thrombotic events during the last 6 months * Suspicion or known PRCA (pure red cell aplasia) * Transfusion of white blood cells or packed red blood cells (more than 2 packs) within 4 weeks and any transfusion of white blood cells or packed red blood cells within 2 weeks prior to randomization (visit 0) * Anemia due to overt bleeding or hemolysis within 2 weeks before screening * Erythropoietin or Darbepoietin therapy within 8 weeks before screening, including any investigational form of erythropoietin (e.g. gene-activated erythropoietin, novel erythropoiesis stimulating protein) * Radiation therapy during the study, radiation therapy induced anemia * Therapy with cyclosporine * Chemotherapy which causes predictable treatment with peripheral-blood progenitor therapy, e.g. G-CSF * Clinical evidence of current uncontrolled hyperparathyroidism (serum parathyroid hormone >1500 pg/mL) * Major surgery within 14 days prior to randomization * Treatment with antiepileptics within the last 5 years * Previously diagnosed HIV or acute hepatitis infection * Uncontrolled hypertension, defined as a diastolic blood pressure measurement >110mm Hg during the screening period * History of congestive heart failure (NYHA class III, IV) * Unstable angina pectoris, active cardiac disease, cardiac infarction during the last six months before screening * Evidence of acute infectious disease or serious active inflammatory disease within four weeks before screening (Visit -1) or during the screening/baseline period * Known allergy to one of the ingredients of the test or reference products or hypersensitivity to mammalian-derived products * Pregnancy, breastfeeding women or women not using adequate birth control measures * Patients who participate simultaneously in another clinical study or who have participated in a study in the month preceding the start of this study or previously randomized to this study (except studies with approved medications in an approved indication, with an approved dosing regimen including approved treatment combinations) * Suspicion of any non-compliance

Study Objectives Women with PCOS suffer from anovulation and, as a result, infertility. Efforts to clinically induce ovulation in these women using follicle stimulating hormone (FSH) administered subcutaneously seemingly requires prolonged administration compared to that of ovulatory women without PCOS. The apparent differing ovarian responsiveness to FSH between PCOS and normal women has not been carefully studied. We propose to address this issue by performing a dose-response study and examine ovarian follicle (estrogen, E2) responses to FSH administered subcutaneously in women with PCOS compared to responses observed in normal women. Conditions: Polycystic Ovary Syndrome, Healthy, Anovulation, Hyperandrogenism Intervention / Treatment: DRUG: Recombinant Follicle Stimulating Hormone Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: OTHER Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Subjects determined to have PCOS based on clinical history of irregular menses and clinical or laboratory evidence of hyperandrogenism and polycystic ovaries on ultrasound OR * Subjects determined to have a clinical history of regular periods. Exclusion Criteria: * Women with hemoglobin less than 11 gm/dl at screening evaluation * Women with untreated thyroid abnormalities * Pregnant women or women who are nursing * Women with BMI > 37 * Women with known sensitivity to the agents being used * Women with diabetes, or renal, liver, or heart disease * Women with any hormonal therapy or metformin for at least 2 months prior to study start.

Study Objectives This is a phase I/II study in Japan to evaluate the safety of EMD531444 and its effects on survival time in patients with stage III unresectable non-small cell lung cancer. Conditions: Non-small Cell Lung Cancer Intervention / Treatment: BIOLOGICAL: Tecemotide (L-BLP25), DRUG: Single low dose cyclophosphamide, BIOLOGICAL: Placebo, OTHER: Saline Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Receipt of concomitant or sequential chemoradiotherapy, consisting of a minimum of two cycles of platinum-based chemotherapy and a minimum radiation dose of greater than or equal to (>=) 50 Gray (Gy). Participant must have completed the primary thoracic chemoradiotherapy at least 4 weeks and no later than 12 weeks prior to randomization * Written informed consent given before any study-related activities are carried out. * Histologically or cytologically documented unresectable stage III NSCLC. Cancer stage must be confirmed and documented by Computed Tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) scan * Documented stable disease or objective response, according to RECIST, after primary chemoradiotherapy for unresectable stage III disease, within four weeks 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 Gy * Eastern cooperative Oncology Group (ECOG) performance status of 0 or 1 * Adequate bone marrow function * Greater than or equal to 20 years of age Exclusion Criteria: * Lung cancer-specific therapy (including surgery), other than primary chemoradiotherapy. Note: exploratory surgery before study entry is allowed * 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) received within four weeks prior to randomization * Malignant pleural/pericardial effusion or pleural dissemination or separate tumor nodules in the same lobe at initial diagnosis and/or at study entry * Past or current history of neoplasm other than lung carcinoma, except for adequately 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 five years * Autoimmune disease * A recognized immunodeficiency disease including cellular immunodeficiencies, hypogamma-globulinemia, or dysgammaglobulinemia; participants who have hereditary or congenital/acquired immunodeficiencies * Any preexisting medical condition requiring chronic steroid or immunosuppressive therapy, including presence of diffuse radiation pneumonitis spreading out of the involved field * Known Hepatitis B and/or C * 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 * Pregnant or breast-feeding women. Participants whom the investigator considers may be at risk of pregnancy will have a pregnancy test performed per institutional standard. Male and female subjects who have a reproductive ability, unless using effective contraception as determined by the investigator throughout the study until at least 6 months after the last study treatment * Known drug abuse or alcohol abuse * Legal incapacity or limited legal capacity

Study Objectives This is an observational study to assess patient survival and clinical outcomes after the RenovoCath™ RC120 catheter is used to deliver chemotherapeutic agents to pancreatic tumors. Conditions: Pancreatic Neoplasms Intervention / Treatment: DEVICE: RenovoCath™ R120 Catheter Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * 18 years of age * Diagnosed with unresectable or borderline resectable pancreatic adenocarcinoma confirmed by histology or cytology * Without current myelotoxicity and with sufficient health status to undergo a catheterization procedure * Willing to provide informed consent and comply with the required follow-up. Exclusion Criteria: * Have received prior chemotherapy and/or radiation therapy within 14 days prior to the first intra-arterial treatment. * Currently participating in another active drug or device study or registry protocol that would interfere with this study. * Vulnerable populations: prisoners, pregnant or breastfeeding females.

Study Objectives This is a phase IB/II clinical trial to evaluate the efficacy and safety of SHR6390 in combination with Letrozole or Anastrozole or Fulvestrant. Patients who have HR positive and HER2 negative recurrent/metastatic breast cancer and have not received systemic anticancer therapy are eligible for study. Conditions: Advanced Breast Cancer Intervention / Treatment: DRUG: SHR6390, DRUG: Letrozole or anastrozole or Fulvestrant Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Has the pathologically-confirmed diagnosis of locally recurrent or metastatic, hormone-receptor positive, HER2 negative Breast Cancer. * Age: 18 - 75 years old, postmenopausal women.prepostmenopausal women, but should receive Ovary castration. Inclusion Criteria * Cohort 1 and Cohort 2 :No prior systemic anti-cancer therapy for advanced HR+ disease. Cohort 3 and Cohort 4 : Patients must satisfy the following criteria for prior therapy: * a) Progressed after 2 years during treatment of adjuvant therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre- or perimenopausal. b)Progressed within 12 months of completion of adjuvant therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre- or perimenopausal. c) Progressed while 6 month after the end of prior aromatase inhibitor therapy for advanced/metastatic breast cancer if postmenopausal, or prior endocrine treatment for advanced/metastatic breast cancer if pre- or perimenopausal. * One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy. * Eastern Cooperative Oncology Group [ECOG] 0-1 Measurable disease as per Response Evaluation Criterion in Solid Tumors[RECIST] 1.1 * Adequate organ and marrow function Exclusion Criteria * Confirmed diagnosis of HER2 positive disease * Patients who received any endocrine therapy as neo/adjuvant therapy for breast cancer are eligible. If the neo/adjuvant therapy of any endocrine therapy , the disease-free interval must be greater than 12 months from the completion of treatment until study entry. * Patients who received prior treatment with any CDK4/6 inhibitor, everolimus,fulvestant. * Clinically significant cardiovascular and cerebrovascular diseases,including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, Congestive heart failure (New York heart association (NYHA) class > 2), or ventricular arrhythmia which need medical intervention. * Has known active central nervous system metastases.

Study Objectives The purpose of the study is to establish that sustained estrogen levels are the driving force for the LH surge, and are thereby necessary for ovulation to occur. We predict that by reducing levels of circulating estrogen, letrozole, an aromatase inhibitor, will inhibit ovulation from occurring. Conditions: Ovulation Disorder, Ovarian Cysts Intervention / Treatment: DRUG: Letrozole Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: DIAGNOSTIC Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: TRIPLE

Inclusion Criteria: * Patient having regular menstrual cycles between 26-30 days * Ages 18-40 * Patient must not be sexually active during the study period, or if so must be using a reliable form of non-hormonal birth control including tubal ligation or vasectomy, non-hormonal intrauterine contraceptive device (IUD), or condoms with spermicide. * Willing to participate in study and available for all monitoring visits. * IRB consent Exclusion Criteria: * Patient must NOT have used hormonal contraception three months or less prior to study. * Irregular menstrual cycles (<26 days or >30 days within the last 6 months. * Untreated thyroid dysfunction or hyperprolactinemia * Pregnancy (current or within 3 months) or breastfeeding * Allergy or contraindication to letrozole

Study Objectives We aim to study the effect of local anesthetic when used in conjunction with general anesthesia during thyroidectomy or parathyroidectomy. We hypothesize there is equivalent pain control between bilateral superficial cervical plexus block and local wound infiltration when used in conjunction with a general anesthetic. Conditions: Thyroid Neoplasms, Goiter, Nodular, Thyroid Nodule, Graves' Disease, Hyperparathyroidism Intervention / Treatment: PROCEDURE: Superficial Cervical Plexus Block, PROCEDURE: Local Wound Infiltration, DRUG: 0.9% saline, DRUG: Marcaine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Patient >= 18 years old * Surgical indication for parathyroidectomy or thyroidectomy Exclusion Criteria: * Patients < 18 years old * Patient with history of chronic opioid use * Patient with chronic pain syndromes * Patient with allergy to marcaine

Study Objectives The central hypothesis for this proposal is that multimodal (clinical, imaging, tissue) biomarkers will better predict early brain tumor response to treatments and will be more reliable prognostic markers in patients with malignant brain tumors. Conditions: High Grade Glioma Intervention / Treatment: DRUG: FLT-PET/CT: (3'deoxy-3'-[(18)F] fluorothymidine) PET/CT Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Newly diagnosed or suspected high grade glioma >= 1cm in diameter on postoperative anatomic imaging (contrast MRI), prior to initiation of chemoXRT * Anticipated survival >=6 months * Able to give informed consent * Capable of undergoing MRI and PET scans without the need for sedation or general anesthesia * Male or Female Exclusion Criteria: * Prior radiation therapy and chemotherapy to the brain * Active intracranial infection or nonglial brain mass. * Recent large intracranial hemorrhage (<1 month) * Expected survival <6 months * Pregnant or nursing * Renal failure * Lives far from BWH and/or is unwilling/ unable to return for scheduled imaging visits.

Study Objectives The purpose of this study is to determine whether NK012 is safe and effective in the treatment of advanced and metastatic triple negative breast cancer. Conditions: Triple Negative Breast Cancer Intervention / Treatment: DRUG: NK012 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 or cytologically confirmed diagnosis of breast cancer with locally advanced disease for which there is no surgical option, or stage IV disease. * ER-negative and PR-negative (defined as less than or equal to 10% tumor staining). * HER2-negative defined as one of the following: 1. 0 or 1+ IHC; 2. 2+ or 3+ IHC and FISH negative (ratio < 2.2); 3. or FISH negative (ratio < 2.2). * No less than one and no more than two prior chemotherapy regimens for advanced or metastatic disease. * Prior chemotherapy must have included a taxane either as part of an adjuvant regimen or as part of a metastatic disease regimen. * Interval from last dose of prior treatment to enrollment in this study must be at least 4 weeks for cytotoxic chemotherapy (exception: 6 weeks for nitrosoureas or mitomycin C), 5 half-lives for non-cytotoxic therapy (to be reviewed by the Medical Monitor to establish start date), and 4 weeks for monoclonal antibodies; patients must have recovered from all acute toxicities. * Measurable disease by RECIST. * ECOG performance status of 0-2. * Females at least 18 years of age. * Adequate bone marrow function as defined by absolute neutrophil count of greater than or equal to 1,500/ mm^3 and platelets of greater than or equal to 100,000/mm^3. * AST(SGOT) and ALT(SGPT) levels no greater than 3 x the institutional ULN, and total bilirubin less than or equal to 1.5 x ULN. * Serum creatinine less than or equal to 1.5 x ULN, or creatinine clearance greater than or equal to 60 mL/min (Cockcroft-Gault formula) for patients with serum creatinine levels > 1.5 x ULN. * Able to understand and show willingness to sign a written informed consent document. Exclusion criteria: * Patient has Gilbert's Syndrome. * Concurrent use of other investigational agent. * History of brain metastases or spinal cord compression, unless irradiated a minimum of 4 weeks before study entry and stable without requirement for corticosteroids for > 1 week. * Prior exposure to topoisomerase 1 inhibitors (i.e., irinotecan, topotecan, camptothecin). * Concurrent serious infections requiring parenteral therapy. * Pregnant or of childbearing potential and not using methods to avoid pregnancy. A negative pregnancy test (urine or serum) must be documented at baseline for women of childbearing potential. Patients may not breast-feed infants while on this study. * Significant cardiac disease including heart failure that meets New York Heart Association (NYHA) class III and IV definitions, history of myocardial infarction within one year of study entry, uncontrolled dysrhythmias or poorly controlled angina. * History of serious ventricular arrhythmia (VT or VF, greater than or equal to 3 beats in a row), QTc greater than or equal to 450 msec for men and 470 msec for women, or LVEF less than or equal to 40% by MUGA or ECHO.

Study Objectives RATIONALE: Drugs used in chemotherapy, such as hydroxychloroquine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving hydroxychloroquine together with bortezomib may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of hydroxychloroquine when given together with bortezomib and to see how well it works in treating patients with relapsed or refractory multiple myeloma. Conditions: Multiple Myeloma and Plasma Cell Neoplasm Intervention / Treatment: DRUG: bortezomib, DRUG: hydroxychloroquine 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 multiple myeloma * Documented relapse or continued disease after at least one prior therapy (which may include autologous and allogeneic bone marrow transplantation) * Need for further therapy for myeloma, as determined by the patient's treating physician * Age greater than 18 years Exclusion Criteria * Baseline peripheral neuropathy of grade 2 or higher * History of allergic reactions to compounds of similar chemical or biologic composition to bortezomib or hydroxychloroquine * Prior dose-limiting toxicity with bortezomib * Known macular degeneration or retinopathy (diabetic or otherwise), porphyria, or psoriasis. Patients with well-controlled psoriasis may participate in the study provided that they are under the care of a specialist in this condition who agrees to monitor the patient for exacerbations. * Other conditions that would require therapy with hydroxychloroquine, including but not limited to systemic lupus, rheumatoid arthritis, porphyria cutanea tarda, and malaria treatment or prophylaxis * ECOG performance status >2 (for definition, see section 0) * Life expectancy of less than 3 months * Lack of adequate organ or bone marrow function based on lab values drawn <= 14 days before beginning treatment. * Concurrent treatment with a different investigational regimen. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study. * Treatment with other anti-myeloma agents, including thalidomide or lenalidomide, within the 14 days prior to initiating hydroxychloroquine. Treatment with corticosteroids will be permitted up to 7 days prior to initiating hydroxychloroquine. Corticosteroids that are being used for other diseases are permitted if the dose is less than the equivalent of 20 mg of prednisone daily. Concurrent therapy with bisphosphonates through the study period is permitted at the discretion of the treating physician. Concurrent hematopoietic growth factors are also permitted, including filgrastim or pegfilgrastim, epoetin alpha, and darbepoetin alpha * Known central nervous system involvement. The poor prognosis and progressive neurological dysfunction associated with central nervous system involvement would confound the evaluation of neurological and other adverse events. The presence of calvarial lytic lesions or plasmacytomas is not an exclusion criterion if there is no central nervous system involvement. * Concurrent malignancy other than basal cell carcinoma of the skin, squamous cell carcinoma of the skin, any carcinoma in situ, or localized prostate adenocarcinoma (stage T1a or T1b) with a stable PSA for a period of at least 4 months. Patients with a prior malignancy treated with chemotherapy, biologic agents, and/or radiation are eligible for this study if they have completed therapy >=4 years previously with no evidence of recurrent disease. Patients with a prior malignancy treated with surgery alone are eligible for this study if they have completed therapy >=2 years previously with no evidence of recurrent disease. * Uncontrolled intercurrent illness including, but not limited to: uncontrolled ongoing infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Inability to understand the informed consent document or unwillingness to consent. Written informed consent must be obtained from all patients before study entry. * Pregnancy or breastfeeding. * Unwillingness to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation for men and women of child-bearing potential.

Study Objectives The primary objective of this study is to determine a safe, tolerable and effective dose of sotatercept that results in the greatest frequency of improvement of anemia in patients diagnosed with low- or intermediate-1 risk myelodysplastic syndromes (MDS) or non-proliferative chronic myelomonocytic leukemia (CMML). Conditions: Anemia, Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, Low to Intermediate-1 MDS, Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML) Intervention / Treatment: DRUG: Sotatercept Location: United States, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Men and women >= 18 years of age * Documented diagnosis of myelodysplastic syndromes (MDS) or non-proliferative chronic myelomonocytic leukemia (CMML), white blood cells (WBC) <= 13,000 /mm^3, World Health Organization (WHO) that meets International Prognostic Scoring System (IPSS) criteria for low or intermediate-1 risk disease * Anemia, Hemoglobin (Hgb) <= 9.0 g/dL or >= 2 units of Red Blood Cells (RBCs) within 84 days * No response or loss of response to Erythropoiesis-Stimulating Agents (ESAs) or erythropoetin (EPO) > 500 mU/ml * Eastern Cooperative Group (ECOG) score <=2. * Creatinine < 1.5 * Upper Limit of the Normal (ULN) * Total bilirubin <=3.0 mg/dL * Aspartate aminotransferase (AST)/Serum glutamic oxaloacetic transaminase (SGOT) & Alanine Aminotransferase (ALT)/Serum Glutamic Pyruvic (SGPT) <=3.0 * Upper Limit of Norma (ULN) * Free of metastatic malignancy (other than MDS) for >=2 years * Highly effective methods of birth control for females and males Exclusion Criteria: * Chromosome 5q deletion * Pregnant or breast feeding women and males who do not agree to use condom during the sexual contact with females of childbearing potential * Major surgery within 30 days * Incomplete recovery or incomplete healing of wounds from previous surgery * Heart failure >=3 (New York Heart Association (NYHA)) * Thromboembolic or myocardial infarction event within 6 months * Concurrent anti-cancer cytotoxic chemotherapy * History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant protein * Known positive for Human Immunovirus (HIV) or infectious Hepatitis type C or active infectious Hepatitis type B * Clinically significant anemia unrelated to MDS * Thrombocytopenia (<30,000/uL) * Uncontrolled hypertension * Treatment with another investigational drug or device within 28 days prior to Day 1 * Prior exposure to sotatercept (ACE-011) * Any serious medical condition, lab abnormality or psychiatric illness

Study Objectives This study is a single center, open-label, two-part study to assess image guided surgery of intramolecular imaging in nervous system tumors. Subjects with a diagnosis of a resectable nervous system tumor who are at risk of recurrence are included. The primary goal is to observe what tissues fluoresce in the OR, and then to identify if that tissue is cancerous/tumor or normal when the histopathology is performed. Conditions: Suspected Central Nervous System Tumors Intervention / Treatment: DRUG: Indocyanine Green (ICG), RADIATION: Intraoperative near-infrared (NIR) Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: DIAGNOSTIC Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: Adult patients 18 years of age and older Patients presenting with a CNS tumor presumed to be resectable and are at risk for local recurrence on pre-operative assessment Good operative candidate as determined by the treating physician and multidisciplinary team Subject capable of giving informed consent and participating in the process of consent Exclusion Criteria: Pregnant women as determined by urinary or serum beta hCG within 72 hours of surgery Subjects with a history of iodide allergies Vulnerable patient populations Patients unable to participate in the consent process (children and neonates) Patients with non-MRI compatible implanted metallic foreign bodies Patients who due to severe claustrophobia cannot tolerate MRI scanning Patients with a known allergy or hypersensitivity to MRI contrast agents including gadolinium