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Study Objectives The treatment with oral melphalan and prednisone has been recommended as standard treatment of AL amyloidosis but the results are rather disappointing. Another therapeutic option is pulsed high-dose dexamethasone + melphalan (Mel-Dex) with more encouraging results regarding the achievement of a faster disease response and higher rates of haematological remission. In the last 5 - 10 years, promising treatment outcomes after therapy with high-dose melphalan and autologous stem cell support have been reported by several groups but only highly selected patients are eligible for this treatment. Lenalidomide has been shown to be effective in phase II and III trials in MM patients. Because of the relationship to MM, Lenalidomide is a promising therapeutic option also for patients with AL amyloidosis. The addition of Lenalidomide to Mel-Dex could improve rate of complete response (CR) and organ response in patients not eligible for or refused high-dose chemotherapy. Conditions: Primary Amyloidosis Intervention / Treatment: DRUG: Lenalidomide Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Biopsy proven systemic untreated AL amyloidosis requiring systemic chemotherapy * Not eligible for or refused HDM * Measurable plasma cell disease * Life expectancy > 3 months * WHO performance status < 3 * NYHA < stage IV * Understand and voluntarily sign an informed consent form * Laboratory test results within these ranges Absolute neutrophil count > 1.5 x 109/L Platelet count > 100 x 109/L Creatinine Clearance / MDRD > 40 ml/min Total bilirubin > 2,5 mg/dL * Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study. Exclusion Criteria: * Multiple Myeloma stage II and III (Durie and Salmon) * Previous organ transplantation * Not able to visit the Amyloid Clinic in Heidelberg once per month * Refusal of aspiration of 100 ml bone marrow at study inclusion * Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. * Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide). * Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. * Use of any other experimental drug or therapy within 28 days of baseline. * Known hypersensitivity to thalidomide. * The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs. * Any prior use of lenalidomide. * Concurrent use of other anti-cancer agents or treatments. * Known positive for HIV or infectious hepatitis, B or C. * Patients who are in a depending position of the Sponsor or the Principal Investigator

Study Objectives The aim of this observational study is to describe treatment patterns and effectiveness outcomes in a sample of oncology patients treated for AML with Mylotarg through up to two additional relapsed/refractory (R/R)-based lines of therapy (through third-line therapy). The study will use United States oncology electronic medical record (EMR) data. All study data are secondary data and will have been collected retrospectively from existing clinical data originally collected as part of routine care. Conditions: Leukemia, Myeloid, Acute Intervention / Treatment: DRUG: Gemtuzumab Ozogamicin Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Confirmed diagnosis of acute myeloid leukemia (AML) on or after 01 December 2014 through Clinical Research Nurse (CRN) review of provider documentation of AML diagnosis in the medical record; * Receipt of Mylotarg at any point during first three lines of therapy following initial AML diagnosis; * Age greater than or equal to 18 years at initial diagnosis of AML. Exclusion Criteria: * Record of 1 or more of the following confounding diagnoses at any point before or after AML diagnosis: Acute lymphoblastic leukemia; acute promyelocytic leukemia, aggressive systemic mastocytosis; hypereosinophilic syndrome and/or chronic eosinophilic leukemia; dermatofibrosarcoma protuberans; gastrointestinal stromal tumors.

Study Objectives The purpose of this study is to determine the best dose of vinblastine that can be given with a new drug, temsirolimus. Conditions: Recurrent Lymphoma, Refractory Lymphoma, Solid Tumours, Central Nervous System Intervention / Treatment: DRUG: Vinblastine, DRUG: Temsirolimus Location: Canada 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 histological verification of malignancy at initial diagnosis or at relapse. Note: Histological verification is not required for patients with optic pathway gliomas, or patients with pineal tumours and elevations of CSF or serum tumour markers * Solid tumours (excluding soft tissue sarcomas), CNS and localized brainstem tumours (excluding diffuse intrinsic pontine gliomas (DIPG)) or, * Lymphomas including Hodgkin's disease, non-Hodgkin's lymphoma and post-transplant lymphoproliferative disease (PTLD) * Patients must have relapsed or refractory disease for which there is no known curative therapy, with either measurable or evaluable disease * Age >= 1 year and <= 18 years at time of registration * Performance status: * Patients <= 16 years: Lansky >= 50% * Patients >= 16 years: Karnofsky > 50% Prior Therapy Patients must have received at least one prior regimen prior to registration. There is no limit to the number of prior regimens. Patients must have recovered from the acute effects and reversible toxicities related to prior therapy and have adequate washout prior to study entry as follows: Surgery: Previous major surgery is permitted provided that it has been at least 28 days prior to registration and wound healing has occurred. Additionally, at least 7 days must have elapsed since last biopsy or other minor surgery and wound healing must have occurred. Radiation: Prior radiotherapy is permitted provided that from last dose to registration: * At least 90 days have elapsed from total body irradiation, craniospinal radiotherapy or if >= 50% radiation of pelvis. * At least 6 weeks have elapsed from other substantial bone marrow irradiation. * At least 2 weeks have elapsed from local palliative radiotherapy (small port), * At least 8 weeks have elapsed from 131I-MIBG therapy for neuroblastoma. Chemotherapy: Prior myelosuppressive chemotherapy is permitted provided that it has been at least 3 weeks (6 weeks if nitrosurea) from last administration. Prior therapy with vinblastine, mTOR inhibitors (such as temsirolimus or sirolimus) is permitted provided patients did not develop progressive disease during treatment and patients have never had to discontinue treatment due to severe adverse events such as interstitial lung disease. At least 3 weeks must have elapsed from the last administration of these agents and registration. Other Therapy: Patients may have received other therapies provided that an adequate time has elapsed from completion of therapy/last dose as follows: * At least 60 days from stem cell transplant/rescue without total body irradiation and no signs of graft-versus-host disease (GVHD). * At least 7 days (2 weeks for peg-filgrastim) from completion of therapy with hematopoietic growth factors. * At least 3 half-lives from last administration of monoclonal antibodies. * At least 6 weeks from any other immunotherapy (e.g. vaccines). * For biologic anti-neoplastic agents, the longer of the following must have elapsed from last administration prior to study entry: At least 2 weeks or, Standard cycle length of prior regimen or, 5 half-lives. - Adequate Bone Marrow Function, defined as: * Absolute neutrophil count (ANC) >= 1.0x10^9/L. * Platelets >= 100 x 10^9/L (transfusion independent defined as not receiving platelet transfusions within 7 days prior to registration). * Hemoglobin > 80 g/L (may receive RBC transfusions). Patients with known bone marrow disease will be eligible for the study provided they meet bone marrow criteria above and they are not known to be refractory to red cell or platelet transfusions. - Adequate Renal Function, defined as: * Measured creatinine clearance/GFR >= 70 mL/min/1.73 m2 OR, * Serum creatinine <= 1.5 x ULN for age. - Adequate Liver Function, defined as: * Total bilirubin <= 1.5 x upper limit normal for age. * ALT <= 1.5 x upper limit of normal. * Serum albumin >= 20 g/L. - Adequate Metabolic Function, defined as: * Serum triglyceride level <= 3.42 mmol/L (300 mg/dL). * Serum cholesterol level <= 7.75 mmol/L (300 mg/dL). * Blood glucose <= ULN for age. Initial sampling may be random; if abnormal, fasting blood glucose must be obtained and be within the upper normal limits for age. * Adequate Pulmonary Function, defined as: * No dyspnea at rest. * O2 saturations of >= 92% on room air. * Patients with any baseline respiratory symptoms, or with a history of pulmonary toxicity, and who are old enough to complete pulmonary function tests, should have documented FEV1 and vital capacity >= 50% normal value. * Electrolytes: <= grade 1 (Potassium, Calcium, Magnesium, Phosphate) * Patient or guardian consent must be obtained on all patients according to local Institutional and/or University Human Experimentation Committee requirements. Children > 8 years old whose parent or guardian has signed consent on their behalf may also sign assent if desired * Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre * In accordance with NCIC CTG policy, protocol treatment is to begin within 5 working days of patient registration Exclusion Criteria: * Patients with serious illness or medical condition that would not permit the patient to be managed according to the protocol including, but not limited to: 1. Active or uncontrolled infections; 2. Uncontrolled diabetes; 3. Any other medical conditions that might be aggravated by treatment; 4. History of an underlying inherited or ongoing bleeding disorder; 5. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events (e.g. heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age) or mean resting corrected QT interval (QTc) > 470 msec). * Patients with a history of allergic reactions or known hypersensitivity to the study drug(s) or their components, or compounds of similar chemical or biologic composition. * Patients with lymphoma or solid tumours (except primary CNS tumours) who have untreated brain metastases, untreated spinal cord compression or meningeal metastases are not eligible (CNS imaging is not required to rule this out unless there is a clinical suspicion of CNS disease). Patients with treated brain metastases who have radiologic evidence of stable brain metastases, with no evidence of cavitation or hemorrhage in the brain lesion, are eligible providing that they are asymptomatic. If being treated with corticosteroids, must be at a stable or decreasing dose for at least 7 days prior to study entry. * Concurrent Medications * Patients receiving other investigational agents. * Patients receiving other anti-cancer agents, or radiation therapy. * Patients receiving angiotensin-converting enzyme (ACE) inhibitors. * Patients receiving QT/QTc-prolonging drugs. * Patients receiving anticoagulants. * Patients receiving anti-GVHD or agents to prevent organ rejection post-transplant. * Patients receiving strong/potent CYP3A4/5 substrates/inhibitors/inducers. These agents must have been discontinued for at least 14 days prior to registration. Grapefruit juice is also not permitted for at least 14 days prior to registration and at any time during study participation. * Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method. Pregnant or breast feeding females will not be entered on this study due to the potential fetal and teratogenic adverse events. * Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.

Study Objectives To explore overall response rate of trastuzumab combined with TS-ONE based chemotherapy in first-line HER2-positive advanced gastric cancer. Conditions: HER 2 Positive Advanced Gastric Cancer Intervention / Treatment: DRUG: Trastuzumab, TS ONE, Cisplatin Location: Singapore Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must have histologically or cytologically confirmed adenocarcinoma of the stomach and Gastric-esophageal junction. * 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 more than or equals to 20 mm with conventional techniques or as more than or equals to 10 mm with spiral CT scan. * Patients without prior systemic treatment. Patients who completed postoperative adjuvant chemotherapy (and radiotherapy) more than 180 days before may be enrolled. * Age more than or equals to 21 years. * Life expectancy of greater than 3 months. * ECOG performance status less than or equals to 2 (Karnofsky more than or equals to 60%). * Patients must have normal organ and marrow function as defined below: * Hemoglobin > 8.0 g/dL * Leukocytes > 3,000/mcL * Absolute neutrophil count > 1,500/mcL * Platelets > 100,000/mcL * Total bilirubin less than or equals to 1.5 X ULN * AST (SGOT)/ALT (SGPT) less than or equals to 3 x institutional upper limit of normal * ALP less than or equals to 3 x upper limit of normal* * Creatinine within normal institutional limits OR Creatinine clearance** >60 mL/min for patients with creatinine levels above institutional normal * In the presence of liver metastasis, patients with AST, ALT and ALP < or = 5 x the upper limit of normal may be admitted. *In the presence of bone metastasis, patients with AST ,ALT and ALP < or = 10x the upper limit of normal maybe admitted. **: Creatinine clearance can be estimated using Cockcroft-Gault formula man: Ccr (mL/min) = body weight (kg) x (140 - age)/(72 x serum creatinine (mg/dL)), woman: Ccr = male Ccr x 0.85]. The above CrCl Formula is to be applied in all sites. * Patients who have HER2-positive cancer confirmed with IHC and/or FISH***. *** Immunohistochemistry (IHC) for HER-2 is routine as part of pathological evaluation of gastric hybridisation (FISH) for Her2 copy number is required. A copy number value above 2.2 is taken as positive. The sponsors for the drugs used in our investigator initiated trial (Taiho) have kindly agreed to pay for the HER2 FISH test. * Patients able to take orally. * Patients with left ventricular ejection fraction of at least 50% on MUGA or 2D-echocardiography done within 28 days before enrollment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * The effects of proposed regimen on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because antitumor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. * Ability to understand and the willingness to sign a written informed consent document. * Consent for fresh frozen tissue collection, mandatory for patients with primary in-situ tumors and optional for patients without primary in-situ tumors. * Tissue collection only applicable to National Cancer Centre (S) and National University Hospital (S) Exclusion Criteria: * Patients who have had radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to treatment administered more than 4 weeks earlier. * Patients receiving any other investigational agents. * Patients with known brain metastases. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to TS-ONE, cisplatin and trastuzumab or other agents used in the study. * Presence of any contraindications to TS-ONE or cisplatin or trastuzumab. * Baseline LVEF (Left Ventricular Ejection Fraction) < 50%. * Patients with serious (e.g.inpatient care is needed) complications (e.g. intestinal paralysis, intestinal occlusion, interstitial pneumonia or pulmonary fibrosis, poorly-controlled diabetes, renal failure or hepatic cirrhosis). * Patients with massive ascites (moderate or higher, beyond the pelvic cavity and retention on the anterior surface of the liver on CT) or massive pleural effusion retention. * Patients with fresh bleeding from the digestive tract which needs repeated blood transfusion. * Patients with diarrhea (4 or more times per day or watery diarrhea). * Previous malignancy other than gastric cancer diagnosed in the last 5 years except for basal cell carcinoma of skin or preinvasive cancer of cervix. * Patients with reproductive potential who refuse to use an adequate means of contraception (including male patients). * Significant disease or conditions which, in the investigator's opinion, would exclude patient from the study. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant or lactating female. * HIV-positive patients.

Study Objectives This study will evaluate bioavailability and food effect of selumetinib (AZD6244) in healthy male participants. A total of 24 healthy male participants will be included to ensure at least 20 evaluable participants. The study is divided in 2 study parts; the same participants will participate in both parts of the study. Part 1 of the study is to investigate the pharmacokinetics (PK) of the selumetinib granule compared to the PK of selumetinib capsule, when administered with water under the fasted conditions. Part 2 of the study is to investigate the PK of selumetinib granule and capsule under fed conditions. Participants will also receive a single 500 mg dose of acetaminophen at the same time as selumetinib administration. Conditions: Neurofibromatosis Type 1 (NF1)-Related Plexiform Neurofibromas (PNs), Healthy Participants Intervention / Treatment: DRUG: Treatment A, DRUG: Treatment B, DRUG: Treatment C, DRUG: Treatment D, DRUG: Acetaminophen Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria * Provision of signed and dated, written informed consent before any study-specific procedures. * Healthy male participants aged 18 to 45 years (inclusive) with suitable veins for cannulation or repeated venipuncture. * Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg. * Participants is able to consume a low-fat meal within a 30-minute period. * Participants has a creatinine clearance (CRCL) greater than 50 mL/min using Cockcroft-Gault formula. * Participants is willing to comply with contraception requirements as described below: * Male participants with sexual partners who can become pregnant (i.e., women of childbearing potential) must use 2 highly-effective methods of contraception, one of which must be a barrier method (condom with spermicide) from the time of the first administration of the IMP until 12 weeks after the last administration of the IMP to avoid pregnancy and/or potential adverse effects on the developing embryo. * Participants with sexual partners who are pregnant must use an effective method of contraception (barrier method) from the time of the first administration of the IMP until 12 weeks after the last administration of the IMP. * Participants must avoid sperm donation during the study and for 12 weeks after the last administration of the IMP. * Reliable methods of contraception must be used consistently and correctly. * Reliable methods of contraception for participants include: Use of barrier methods (condom and spermicide) for the duration of the study until 12 weeks after the last administration of the IMP. * Acceptable methods for participants partners include: 1. Use of implants, injectables and combined oral contraceptives (must be used in combination with a barrier method of contraception) 2. Use of intrauterine devices (must be used in combination with a barrier method of contraception) Exclusion Criteria : * Participants of Japanese, non-Japanese Asian or Indian ethnicity. * Participants has any one parent or grandparent (maternal or paternal) that was Japanese or non-Japanese Asian (e.g., China, Taiwan, Korea, Philippines, Thailand, Vietnam and Malaysia) or Indian. * History or presence of central serous retinopathy or retinal vein thrombosis, IOP greater than 21 mmHg or uncontrolled glaucoma. * History of any clinically significant disease or disorder which, in the opinion of the PI, may put the participant at risk because of participation in the study, influence the result of the study or influence the participants ability to participate in the study. * Participant has ophthalmologic conditions as follows: * Current or past history of central serous retinopathy/retinal pigment epithelial detachment or retinal vein occlusion. * Intra-ocular pressure > 21 mmHg or uncontrolled glaucoma (irrespective of IOP). * Participant has any cardiac conditions as follows: * Uncontrolled hypertension (BP >= 150/95 mmHg despite medical therapy). * Acute coronary syndrome within 6 months before starting treatment. * Uncontrolled Angina - Canadian Cardiovascular Society grade II-IV despite medical therapy. * Symptomatic heart failure New York Heart Association (NYHA) Class II-IV, prior or current cardiomyopathy, or severe valvular heart disease. * Prior or current cardiomyopathy including but not limited to the following: 1) Known hypertrophic cardiomyopathy. 2) Known arrhythmogenic right ventricular cardiomyopathy. 3) Previous moderate or severe impairment of LVEF < 45% on echocardiography even if full recovery has occurred. * Left ventricular ejection fraction below the lower limit of normal (LLN) or < 55% measured by ECHO at the Screening Visit. * Severe valvular heart disease. * Atrial fibrillation with a ventricular rate > 100 beats per minute (bpm) on ECG at rest. * QTcF > 450 ms or other factors that increase the risk of QT prolongation. * Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP. * Any clinically relevant abnormal findings in physical examination, hematology, clinical chemistry, urinalysis, vital signs or ECG at the Screening Visit, which in the opinion of the PI, may put the participant at risk because of his participation in the study. Test may be repeated twice at the discretion of the Investigator if abnormal. * Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody. * A suspected/manifested infection according to the International Air Transport Association (IATA) Categories A and B infectious substances. * History of, or current alcohol or drug abuse, as judged by the principal investigator (PI). * Participation in another clinical study (investigational product administered within 30 days before the Screening Visit, or participation in a method development study [no drug] 30 days before the Screening Visit). Participation is defined as the completion of a treatment related visit. * Planned in-patient surgery, dental procedure or hospitalization during the study. * Plasma donation within 30 days of the Screening Visit or any blood donation/loss more than 500 mL during the 90 days before the Screening Visit. * A definite or suspected personal history of intolerance or hypersensitivity to drugs and/or their excipients, judged to be clinically relevant by the PI. * Known severe hypersensitivity to selumetinib or acetaminophen or any excipient of these medicinal products or history of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib. * Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 90 days before the Screening Visit. * Positive screen for drugs of abuse, alcohol or cotinine at the Screening Visit or on each admission to the Clinical Unit or positive screen for alcohol on each admission to the Clinical Unit. * Use of drugs with enzyme-inducing properties such as St John's Wort within 4 weeks before the first administration of IMP. * Use of any prescribed medicine and over-the-counter (OTC) drugs (including herbal remedies, vitamins and minerals) within 2 weeks or 5 times the half-life, whichever is the longer, of the respective drug before Day -1 or Treatment Period 1. No medications known to prolong the QT/QTc interval are allowed. * Excessive intake of caffeine-containing drinks or food e.g., coffee, tea, chocolate, Red Bull or cola (more than 6 units of caffeine per day). One caffeine unit is contained in the following items: 1 (6 oz) cup of coffee, 2 (12 oz) cans of cola, 1 (12 oz) cup of tea, ½ (4 oz) cup of energy drink (e.g., Red Bull) or 3 oz of chocolate. * Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the PI. * Involvement of any AstraZeneca, PAREXEL or Clinical Unit employee or their close relatives. * Participants who have previously been randomized to treatment in the current study. * Judgment by the PI that the participant should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and requirements. * Vulnerable participants , e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.

Study Objectives This is a pharmacogenomic study with carboplatin, paclitaxel and bevacizumab as first line therapy in patients with non-squamous advanced non-small cell lung cancer. Conditions: Nonsquamous Nonsmall Cell Neoplasm of Lung Intervention / Treatment: DRUG: paclitaxel, carboplatin and bevacizumab Location: Spain Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Patients should sign inform consent before inclusion in the study that specifies that the clinical treatment entails consent for the analysis of biological samples of tumor and blood. * Histologically confirmed diagnosis of advanced non small-cell lung carcinoma, non-squamous cell * Patients age 18 years or more * Patients will be candidates to received a first line of chemotherapy of carboplatin, paclitaxel and bevacizumab as the best therapeutic option. * Evidence of measurable disease per Response Evalutation Criteria in Solid tumors (RECIST) * Patients must be avalaible for clinical follow-up * Patients with the following hematologic/biochemical values: * Absolute Neutrophil Count ANC > 1500/µl. * Platelets > 100.000 /µl. * Hemoglobine > 10 g/dl. * Bilirrubin < 1.5 mg/dl. * Aspartate aminotransfereasa (AST) and Alanine transaminase (ALT) <= 3 x LSN, except in case of hepatic metastases: upper 5 x LSN * Creatinine clearance >= 45 ml/min. Exclusion Criteria: * Previous treatment for advanced disease. Chemotherapy is allowed if the initial diagnosis of the patient is limited disease and the patient has received adjuvant or neadjuvant treatment * history of haemoptysis (defined as at least half a teaspoon's emission of red blood) in the 3 months prior to inclusion * evidence by CT of tumor cavitations, or tumours invading or abutting major blood vessels * Known or suspected brain metastases non-treated. * Major surgery within 28 days of starting treatment. * Minor surgery within 24 hours before starting the treatment. * Non-controlled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg). * Patients with coronary disease or uncontrolled arrhytmia, uncontrolled cerebrovascular disease and other clinical conditions that, in judgment of the investigator, contraindicate the patient's participation in the study. * History or evidence of bleeding diathesis or hereditary coagulopathy. * Contraindication or suspected allergy to the products under investigation in the study:: paclitaxel, carboplatine or bevacizumab. * Patients who are pregnant or breasfeeding. Women of childbearing potencial must have a negative pregnancy test performed within 7 days before the onset of treatment. * Substance abuse of clinical, psychological or social conditions that can undermine the validity of the informed consent or protocol compliance

Study Objectives The purpose of this study is to evaluate the effect of food on the pharmacokinetics (PK) of the experimental drug, entinostat, in women with breast cancer and men and women with non-small cell lung cancer. The safety and tolerability of entinostat will also be evaluated when entinostat is given by itself as well as with the approved drugs, exemestane (Aromasin®) or erlotinib (Tarceva®). A biomarker (chemical "marker" in the blood/tissue that may be related to your response to the study drug) will also be tested. Conditions: Lung Cancer, Non Small Cell Lung Cancer (NSCLC), Breast Cancer, Estrogen Receptor Breast Cancer Intervention / Treatment: DRUG: entinostat, DRUG: entinostat, DRUG: Erlotinib, DRUG: Erlotinib, DRUG: Exemestane, DRUG: Exemestane Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: Breast Cancer Patients Only * Postmenopausal female patients * Histologically or cytologically confirmed ER+ breast cancer at initial diagnosis and now has current disease progression and is a candidate to receive exemestane NSCLC Patients Only: * Cytologically or histologically confirmed NSCLC of stage IIIb or IV * Received 1 to 2 prior chemotherapy or chemoradiotherapy regimens for advanced NSCLC (excluding erlotinib and valproic acid) and now has disease progression and is a candidate to receive erlotinib All Patients: * Age >= 18 years * Patient must have the following laboratory parameters at study screening: Hemoglobin >= 9.0 g/dL; unsupported platelets >= 100.0 10-9/L; ANC >= 2.0 x 10-9/L; Creatinine less than 2.5 times the upper limit of normal for the institution; AST and alanine transaminase (ALT) < 2.5 times the upper limit of normal for the institution * Patients may have a history of brain metastasis as long as certain criteria are met Exclusion Criteria: * Pregnant or lactating women * Patient has rapidly progressive or life-threatening metastases. * Patient has had previous treatment with entinostat or any other HDAC inhibitor including valproic acid * Patient has a concomitant medical condition that precludes adequate study treatment compliance or assessment, or increases patient risk in the opinion of the investigator, such as but not limited to: MI or arterial thromboembolic events within 6 months, or experiencing severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease and a QTc interval > 0.47 seconds. Uncontrolled heart failure or hypertension, uncontrolled diabetes mellitus, uncontrolled systemic infection. * Patients with another active cancer (excluding adequately treated basal cell carcinoma or cervical intraepithelial neoplasia [CIN / cervical carcinoma in situ] or melanoma in situ). Prior history of other cancer is allowed, as long as there is no active disease within the prior 5 years.

Study Objectives Phase Ib/II, single-arm study of AZD6094 (Volitinib) in combination with docetaxel, in advanced gastric adenocarcinoma patients with MET amplification as a second-line treatment. Phase Ib:Investigational product, dosage and mode of administration Volitinib is an orally available, potent, selective, small molecule c-MET inhibitor. Volitinib should be administered at least 200mg orally once a day in 21 days for achieving appropriate antitumor activity. Docetaxel 60 mg/m2 will be administered via intravenous access once every 3 weeks Phase II: Investigational product, dosage and mode of administration Volitinib is an orally available, potent, selective, small molecule c-MET inhibitor. Subjects will receive Volitinib once daily ( at the MTD determined from Phase Ib) for 21 days as one cycle. Docetaxel 60 mg/m2 will be administered via intravenous access once every 3 weeks. Conditions: Advanced Gastric Adenocarcinoma Intervention / Treatment: DRUG: AZD6094, DRUG: docetaxel Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Provision of fully informed consent prior to any study specific procedures. * Patients must be >=20 years of age. * For Phase Ib: Have histologically or cytologically confirmed diagnosis of relapsed or refractory locally advanced or metastatic solid tumors for whom no alternative effective standard therapy is available or for whom standard therapy is considered unsuitable or intolerable. - Although it is preferred to enroll patients with solid tumors harboring MET amplification, this will not be an enrollment requirement. For Phase II: Advanced gastric adenocarcinoma (including GEJ expand and maybe include in list of abbreviations) that has progressed during or after first-line therapy. * The 1st line regimen must have contained doublet 5-fluoropyrimidine and platinum based regimen. * Relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy containing doublet 5-fluoropyrimidine and platinum-based regimen could be considered as 1st line therapy. * Patients with gastric adenocarcinoma harboring MET amplification by MET FISH. * Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months prior to starting the 1st line therapy. * Provision or availability of biopsy sample for analysis; e.g mandatory pre-treatment biopsy, or available diagnostic biopsy of sufficient quantity/quality * Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations. * ECOG performance status 0-1. * Patients must have a life expectancy >= 3 months from proposed first dose date. * Patients must have acceptable bone marrow, liver and renal function measured within 28 days prior to administration of study treatment as defined below: * Haemoglobin >=9.0 g/dL (transfusion allowed) * Absolute neutrophil count (ANC) >= 1.5 x 109/L * White blood cells (WBC) > 3 x 109/L * Platelet count >=100 x 109/L (transfusion allowed) * Total bilirubin <= 1.5 x institutional upper limit of normal (ULN) (does not include patients with Glibert's disease) * AST (SGOT)/ALT (SGPT) <= 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be <= 5x ULN * Serum creatinine <=1.5 x institutional ULN * At least one measurable lesion that can be accurately assessed by imaging or physical examination at baseline and follow up visits. * Negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1 for women of childbearing potential. * Provision of consent for mandatory biopsy at progression. (fresh frozen will be mandatory if clinically feasible) Exclusion Criteria: * More than one prior chemotherapy regimen (except for adjuvant/neoadjuvant chemotherapy with more than 6 month wash out period) for the treatment of gastric cancer in the advanced setting. * Any previous treatment with MET inhibitors * Any previous treatment with docetaxel. * Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for <=5 years. * HER2 positive patients (defined by HER2 3+ by immunohistochemistry or HER2 SISH +) * Patients unable to swallow orally administered medication. * Treatment with any investigational product during the last 28 days before the enrollment (or a longer period depending on the defined characteristics of the agents used). * Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 3 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment. * With the exception of alopecia, any ongoing toxicities (>CTCAE grade 1) caused by previous cancer therapy. * Intestinal obstruction or CTCAE grade 3 or grade 4 upper GI bleeding within 4 weeks before the enrollment. * Resting ECG with measurable QTcB > 480 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome. * Patients with cardiac problem as follows: uncontrolled hypertension (BP >=150/95 mmHg despite medical therapy) Baseline Left ventricular ejection fraction below the LLN of <55% measured by echocardiography or institution's LLN for MUGA, Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest , Symptomatic heart failure (NYHA grade II-IV), Prior or current cardiomyopathy, Severe valvular heart disease, Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy), Acute coronary syndrome within 6 months prior to starting treatment * Female patients who are breast-feeding or child-bearing and Male or female patients of reproductive potential who are not employing an effective method of contraception * Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses or renal transplant, including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV) * Patients currently receiving (or unable to stop use at least 2 weeks) prior to receiving the first dose of AZD6094, medications known to be potent inhibitors of CYP1A2 or CYP3A4, potent inducers of CYP3A4 or CYP3A4 substrates with a narrow therapeutic range.

Study Objectives The study hypothesis is that metronomic treatment is more efficient than standard treatment. Conditions: Breast Cancer Intervention / Treatment: DRUG: Arm B Vinorelbine (Navelbine oral) Capecitabine (Xeloda), DRUG: Arm A Vinorelbine (Navelbine oral) Capecitabine (Xeloda) Location: Denmark Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Locally advanced or metastatic Human Epidermal Growth Factor Receptor2-Negative breast cancer * WHO performance status < 3 Exclusion Criteria: * Former treatment with Capecitabine or Vinorelbine * Patients who have received more than one line of chemotherapy for metastatic disease * Brain metastases * Malabsorption syndrome * Abnormal organ function * pregnant or lactating women

Study Objectives The ability of sildenafil to aid in the return of erections after nerve-sparing radical prostatectomy has been established. Patients who had either one or both neurovascular bundles spared demonstrated dramatically better responses to "as needed" sildenafil than those that did not, and a positive erectile response to sildenafil was only seen in patients in whom at least one NVB was spared. This study has been designed to determine if sildenafil taken nightly works better than sildenafil on as "as needed" basis for the return of erectile function. The investigators hypothesis is that sildenafil taken nightly promotes a more rapid return of erectile function after nerve-sparing laparoscopic radical prostatectomy. Conditions: Prostate Cancer Intervention / Treatment: DRUG: Sildenafil Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Allocation: RANDOMIZED Interventional Model: SINGLE_GROUP Masking: DOUBLE

Inclusion Criteria: * Male sex * Age < 65 * IIEF erectile function domain score > 26 (out of 30 points possible for this subscale) * Steady sexual partner * Untreated prostate cancer TNM stage < cT2bNxMx (cT1a, cT1b, cT1c, cT2a) and Gleason grade < 8. * Willingness to participate in a clinical trial as manifested by informed consent * Actually undergo nerve-sparing LRP surgery Exclusion Criteria: * Not fulfilling all of the criteria for entry above * Any prior prostate cancer treatment (radiation, hormonal deprivation, chemotherapy) * Contraindication to sildenafil (e.g. nitrates, hypersensitivity) * Existing PDE5 inhibitor requirement for functional erection (e.g. for intercourse) preoperatively * Obstructive sleep apnea

Study Objectives An open, dose-ranging, multiple dose, multi-centre study in patients with Stage I-III or Stage IV gastric cancer. Twelve patients in each of 5 treatment groups were to receive three injections at weeks 0, 2 and 6 with provision for a single booster injection in an extension study period. Conditions: Gastric Cancer Intervention / Treatment: DRUG: G17DT Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: Stage I-III Criteria- * Patients aged 18 years or over who had had a macroscopically curative resection for gastric adenocarcinoma. * Absence of metastatic disease evident from: * physical examination * the most recent chest X-ray * abdominal CT or ultrasound scan * Life expectancy of at least 3 months * WHO performance status of 0 to 1 * Written informed consent given Stage IV Criteria- * Patients aged 18 years or over with Stage IV gastric cancer: carcinoma with the primary tumour invading the adjacent structures and/or involvement of more than 15 regional lymph nodes and/or distant metastases * Life expectancy of at least 3 months * WHO performance status of 0 to 2 * Written informed consent given Exclusion Criteria: * History of other malignant disease except non-melanomatous skin cancer or in situ carcinoma of the uterine cervix Recurrent gastric cancer following previous surgery Presence of metastatic disease: peritoneal deposits or involved lymph nodes outside the limit of resection * Previous use, concomitant use or anticipated use in the period of the study, of any anti-cancer therapies * Concomitant use of immunosuppressants, including systemic (ie oral or injected) corticosteroids * Females who were pregnant, planning to become pregnant or lactating * Patients who were taking part in another study involving an investigational or licensed drug or device in the three months preceding enrolment or during this study * Previous G17DT treatment * Haematological indicators: * Haemoglobin <10.0g/dl * White blood cell count <4.0 x 109/l * Platelets <100 x 109/l

Study Objectives This study will be looking at the objective response rate (ORR) as measured by RECIST in in patients with mismatch repair-proficient (MMR-p), advanced colorectal cancer that treated with CY/GVAX in combination with Pembrolizumab. Conditions: Metastatic Colorectal Cancer Intervention / Treatment: DRUG: CY, BIOLOGICAL: GVAX, DRUG: 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: * Documented mismatch repair-proficient cancer of colorectum, who have received at least two prior lines of therapy for metastatic disease * Measurable disease by RECIST v1.1 * Age >18 years * ECOG Performance Status of 0 to 1 * Estimated life expectancy of greater than 3 months. * Adequate organ function as defined by study-specified laboratory tests * Must use acceptable form of birth control through the study and for 120 days after final dose of study drug * Signed informed consent form * Willing and able to comply with study procedures Exclusion Criteria: * Has a known additional malignancy that is progressing or requires active treatment. * Has known central nervous system (CNS) metastases and/or carcinomatous meningitis. * Has known malignant small bowel obstruction within the last 6 months. * Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, immune or other medical conditions. * Systemically active steroid use. * Has an active infection requiring systemic therapy. * Has a known history of active TB (Bacillus Tuberculosis). * Infection with HIV or hepatitis B or C. * Has history of (non-infectious) pneumonitis that required steroids. * Must not require supplemental oxygen or have a pulse oximetry < 92% on room air. * Conditions, including therapy, laboratory abnormalities, psychiatric or substance abuse disorders, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures. * Pregnant or lactating. * Another investigational product within 28 days prior to receiving study drug. * Major surgery or significant traumatic injury (or unhealed surgical wounds) occurring within 28 days prior to receiving study drug. * Chemotherapy, radiation, hormonal, or biological cancer therapy within 28 days prior to receiving study drug. * Has received a live vaccine within 30 days of planned start of study therapy. * Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, etc.). * Patients receiving growth factors including, but not limited to, granulocyte-colony stimulating factor (G-CSF), GM-CSF, erythropoietin, within 14 days of study drug administration. * Hypersensitivity to pembrolizumab or any of its excipients. * Patient has a known or suspected hypersensitivity to GM-CSF, hetastarch, corn, dimethyl sulfoxide, fetal bovine serum, trypsin (porcine origin), yeast or any other component of GVAX vaccine. * Presence of any tissue or organ allograft and history of allogeneic hematopoietic stem cell transplant. * Unwilling or unable to comply with study procedures.

Study Objectives Aim of the study is to establish in a prospective, randomized clinical trial the activity of primary chemotherapy containing high dose-methotrexate, alone or combined with high dose cytarabine, in patients with primary central nervous system lymphoma Conditions: Lymphoma, B Cell Intervention / Treatment: DRUG: high dose methotrexate, DRUG: high dose cytarabine, RADIATION: radiotherapy Location: Switzerland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histological or cytological diagnosis of non-Hodgkin's lymphoma. * Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy. * Disease exclusively localized into the central nervous system, cranial nerves or eyes. * Untreated patients (patients treated with steroids alone are eligible). * At least one measurable lesion. * Age 18 - 75 years. * ECOG performance status < 3 * HBsAg-negative and Ab anti-HCV-negative serologic status. * No known HIV disease or immunodeficiency. * Adequate bone marrow (PLT > 100000 mm3, Hb >= 9 g/dl, ANC >= 2.000 mm3), renal (creatinine clearance >= 60 mL/min), cardiac (VEF >= 50%), and hepatic function (total serum bilirubin < 3 mg/dL, AST/ALT and gGT < 2 per upper normal limit value). * No previous or concurrent malignancies with the exception of surgically cured cervical intraepithelial neoplasia type 1 (CIN1) or localized non-melanomatous skin cancer and of other cancers without evidence of disease since at least 5 years (patients with a previous lymphoma diagnosis will be excluded). * Absence of any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. * Non-pregnant and non-lactating status for female patients. Adequate contraceptive measures during study participation for sexually active patients of childbearing potential. * No concurrent treatment with other experimental drugs. * Informed consent signed by the patient before registration

Study Objectives The study will examine the effect of aminolaevulinic acid (ALA) photodynamic therapy (PDT) of cervical precancerous lesions in women. Conditions: Cervical Persistent High Risk HPV Infection, Cervical Intraepithelial Neoplasia Intervention / Treatment: DRUG: Aminolaevulinic acid photodynamic therapy Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Premenopausal women, 25-50 years of age * Meet one of the 3 following conditions: high-risk HPV-DNA persistently positive for at least 6 months, without CIN or higher grade lesions as verified by cervical biopsy within the last 3 months; CIN1 as verified by cervical biopsy within the last 3 months and high-risk HPV-DNA positive; CIN2/3 as verified by cervical biopsy within the last 3 months, with intense desire to retain the cervical structure or function * Satisfactory colposcopy examination (visibility of entire transformation zone and entire lesion margin ) and endocervical curettage negative * In good health condition as confirmed by past medical history, physical examination, electrocardiogram, laboratory tests and urinalysis on the screening and baseline evaluation within the last 4 weeks of the onset of the study * Meet the following conditions: pregnancy test negative; no pregnancy plan during the trial;no sexuality or reliable contraceptive measures taken since last menstruation to the onset of the study, agreeing to adopt reliable contraceptive measures during the study * Written informed consent signed Exclusion Criteria: * Atypical glandular cells of undetermined significance (AGUS) or adenocarcinoma in situ (AIS) on cytology ,or malignant cells on cytology or histology, or other suspicion of either micro-invasive or invasive disease * Invasive carcinoma possibility or positive endocervical curettage on colposcopy * Severe pelvic inflammatory disease, severe cervicitis, or other severe gynaecological infection as per clinical examination * Undiagnosed vaginal bleeding * With allergic disease at present; known or suspected porphyria; known allergy to ALA or similar compounds * Evidence or history of clinically significant cardiovascular, endocrine, neurologic, pulmonary, hematological, immunological, psychiatric, metabolic disease or other serious diseases * Pregnancy or nursing * Therapeutic drug or other therapeutic measures applied on cervix or rectum within the last 2 weeks of the onset of the study * Participation in any clinical studies within the last 30 days * Subjects that the investigators judged to be not suitable to participate the study besides above

Study Objectives Stage I：preoperative therapy * Capecitabine plus oxaliplatin with concurrent radiotherapy is superior to surgery alone ; Stage II: Perioperative therapy * Perioperative Capecitabine plus oxaliplatin with Concurrent radiotherapy is superior to adjuvant Capecitabine plus oxaliplatin alone; * A regimen of Capecitabine plus oxaliplatin(XELOX) improves survival among patients with incurable locally advanced or metastatic adenocarcinoma of stomach and gastroesophageal cancer . The investigators assessed whether the addition of a perioperative regimen of XELOX regimen with concurrent radiotherapy to adjuvant alone improves R0 resection rate and survival among patients with curable locally advanced adenocarcinoma of stomach and gastroesophageal cancer Conditions: Gastroesophageal Junction Adenocarcinoma Intervention / Treatment: DRUG: Oxaliplatin; Capecitabine, OTHER: Oxaliplatin; Capecitabine; concurrent radiotherapy Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2, PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Disease must be clinically limited to the esophagogastric junction, defined TypeⅡ TypeⅢ(From the endoscopic point of view according to the AEG criteria) * Histologically confirmed primary adenocarcinoma * T2-4 N0-3 M0. T1 tumors are eligible if T1N1-3M0， * ECOG performance status ≦2 AEG is defined and described as tumors which have their center within 5cm proximal or distal of the anatomical cardia. The classification of AEG type I, type II and type III AEG type I: adenocarcinoma of the distal esophagus,which usually arises from an area with specialized intestinal metaplasia of the esophagus, i Barrett's esophagus, and may infiltrate the esophago-gastric junction from above; * AEG type II: true carcinoma of the cardia, arising from the cardia epithelium or short segments with intestinal metaplasia at the esophago-gastric junction; * AEG type III: subcardial gastric carcinoma, which infiltrates the esophago-gastric junction and distal esophagus from below. Exclusion Criteria: * Tis (in-situ carcinoma) and tumors determined to be TIN0 following endoscopy, endoscopic ultrasound and CT scanning. * Patients with primary carcinomas of the esophagus. * Prior chest or upper abdomen radiotherapy, prior systemic chemotherapy within the past 5 years, or prior esophageal or gastric surgery. * Patients with evidence of metastatic disease are not eligible. * Patients with a history of seizure disorder who are receiving phenytoin, phenobarbital, or other antiepileptic medication. * Patients who cannot fully comprehend the therapeutic implications of the protocol or comply with its requirements. * Patients with any medical or psychiatric condition or disease which, in the investigator's judgment, would make the patient inappropriate for entry into this study. * History of hypersensitivity to fluoropyrimidines, capecitabine, oxaliplatin or the ingredients of this product -

Study Objectives This is a non-interventional, multicenter study to evaluate efficacy and safety of intravenous bevacizumab (Avastin) in combination with interferon alpha-2a immunotherapy for first-line treatment in participants with advanced and/or metastatic renal cell cancer (mRCC) in daily routine. Conditions: Renal Cell Cancer Intervention / Treatment: DRUG: Bevacizumab, DRUG: Interferon alpha-2a Location: Germany Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Histologically confirmed advanced and/or metastatic renal cell cancer * No contraindications for Avastin according to summary of product characteristics (SmPC) Exclusion Criteria: *

Study Objectives This phase II trial studies how well pembrolizumab and HER2Bi-armed activated T cells work in treating patients with castration resistant prostate cancer that has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. HER2Bi-armed activated T cells are made using T cells and may target and kill cancer cells. Giving pembrolizumab and HER2Bi-armed activated T cells may work better in treating patients with castration resistant prostate cancer. Conditions: Castration Levels of Testosterone, Castration-Resistant Prostate Carcinoma, Prostate Carcinoma Metastatic in the Bone, PSA Progression, Stage IV Prostate Adenocarcinoma AJCC v7 Intervention / Treatment: BIOLOGICAL: HER2Bi-Armed Activated T Cells, 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: * Be willing and able to provide written informed consent/assent for the trial * Have histologically confirmed prostate adenocarcinoma, with metastases * Progression by either PSA, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for measurable disease or new areas of metastases on bone scan or symptom progression related to prostate cancer despite castrate levels of testosterone; (level < 50 ng/ml) * Be agreeable to continue to maintain castrate levels of testosterone * At least 2 weeks should have elapsed since any immunosuppressive therapy * At least 4 weeks since prior chemotherapy for metastatic disease or at least 2 weeks since prior androgen targeting agents such as ketoconazole, abiraterone, enzalutamide, etc. * Discontinue anti-androgens prior to therapy; at least 6 weeks since last dose of bicalutamide or nilutamide and at least 4 weeks from last dose of flutamide * Have normal bone marrow, renal and hepatic function as deemed by the treating physician and approved by the clinical principal investigator (PI) Dr. Vaishampayan * Not have concurrent anti-cancer therapy * Not have concurrent immunosuppressive therapy or medical condition likely to cause immunosuppression * Have life expectancy > 6 months * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)/Zubrod performance scale * 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 * Within 10 days of treatment registration: Absolute neutrophil count (ANC) >= 1,500 /mcL * Within 10 days of treatment registration: Platelets >= 100,000 / mcL * Within 10 days of treatment registration: Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) * Within 10 days of treatment registration: Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN * Within 10 days of treatment registration: Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN * Within 10 days of treatment registration: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT] =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases * Within 10 days of treatment registration: Albumin >= 2.5 mg/dL * Within 10 days of treatment registration: International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants * Within 10 days of treatment registration: Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Exclusion Criteria: * Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (> 10 mg of prednisone daily or equivalent steroid doses) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment * Has a known history of active TB (Bacillus tuberculosis) * Has hypersensitivity to pembrolizumab or any of its excipients * Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or has not recovered (i.e. =< grade 1 or at baseline) from adverse events due to agents administered earlier; Note: Subjects with =<grade 2 neuropathy are an exception to this criterion and may qualify for the study * Has received major surgery, subject must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy * Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability * Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment * Has known history of, or any evidence of 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 * Father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment * Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent * Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) * Has known active hepatitis B (e.g. hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g. hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) * Has received a live vaccine within 30 days of planned start of study therapy; Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g. Flu-Mist) are live attenuated vaccines, and are not allowed * Has history of cardiac or pulmonary impairment either by clinical history or symptoms or cardiac ejection fraction < 40%

Study Objectives 45 patients undergoing a colon (large bowel/intestine)removal operation for the diagnosis of colon cancer will be included in this study. During colon operation the affected portion of the colon is removed. In addition, lymph nodes are included in the specimen and evaluated by a pathologist. Analysis of the lymph nodes in the specimen are important because this is an important aspect of determining the stage of the cancer. Once the standard technique is used for the colon removal operation and the specimen is removed it will be injected with two drugs to help identify the lymph nodes. One is a blue dye and the other a radiotracer. The colon and ALL of the lymph nodes will then be sent for the standard pathologic evaluation. The patient themselves will never be injected with these drugs being used for research. Following the standard lymph node evaluation, an additional pathologist at an outside research facility will further examine the lymph nodes in the specimen using more in depth techniques which are above and beyond the standard of care. The results of all the pathologic tests will be conveyed to the surgeon of record to help in their decision making regarding further treatment. The study hypothesis is that radiotracer will be at least as effective as blue dye in identifying the lymph nodes most likely to harbor cancer cells (sentinel nodes). Once identified, these sentinel nodes can then undergo a more in depth review leading to improved staging of colorectal cancer and more accurate treatment. Conditions: Colon Cancer, Rectal Cancer Intervention / Treatment: DRUG: Lymphoseek and VBD Sln dissection Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: DIAGNOSTIC Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * The patient has provided written informed consent with Health Insurance Portability and Accountability Act (HIPAA) authorization. * The patient has a diagnosis of colon cancer and is a candidate for surgical intervention, with ex vivo lymph node mapping being a part of the surgical plan. * The patient is at least 18 years of age at the time of consent. * The patient has an Eastern Cooperative Oncology Group (ECOG) performance status of Grade 0 - 2. * The patient has a clinical negative node status at the time of study entry (i.e., Tis-4, N0, M0). Exclusion Criteria: * The patient has clinical or radiological evidence of metastatic cancer including palpably abnormal or enlarged lymph nodes. * The patient has undergone node basin surgery of any type or radiation to the nodal basin(s). * The patient has undergone radiation therapy or chemotherapy treatment within the previous 45 days.

Study Objectives At the end of the study, safety and efficacy outcome measures will be compared to determine a) if dosing with Generic Imiquimod cream, 5% is therapeutically equivalent to the currently marketed Aldara (imiquimod) cream, 5% and b) if both imiquimod 5% creams are superior in comparison to the Vehicle cream. Conditions: Actinic Keratoses Intervention / Treatment: DRUG: imiquimod, DRUG: Aldara™, DRUG: Vehicle Cream Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * Subjects were male or non-pregnant females, 18 years of age or older, in generally good health. Females who were post-menopausal, surgically sterile or using a medically acceptable form of birth control with a negative urine pregnancy test at the Baseline visit. * Subjects provided written and verbal informed consent. * Subjects presented to the clinic with at least 4 but no more than 12 visible, discrete nonhyperkeratotic, nonhypertrophic actinic keratosis lesions within a 25 cm2 Treatment Area on the face and/or anterior scalp. * Subjects were willing and able to comply with study instructions and return to the clinic for required visits. Exclusion Criteria: * Subjects who were lactating, or planning to become pregnant during the study. * Subjects had hyperkeratotic, hypertrophic or large mat-like AKs within the 25 cm2 Treatment Area. * Subjects who had the need or were planning to be exposed to artificial tanning devices or excessive sunlight during the trial. * Subjects who were immunosuppressed (e.g., HIV, systemic malignancy, graft vs. host disease, etc.). * Subjects who experienced an unsuccessful outcome from previous imiquimod therapy. * Subjects with known hypersensitivity or previous allergic reaction to any of the active or inactive components of the study drugs. * Within 2 months: Facial and/or Anterior Scalp: laser resurfacing, photodynamic therapy, chemical peels, dermabrasion, topical application of 5-FU, imiquimod, diclofenac sodium or other treatments for AK or photodamage. * Subjects who used the following systemic, oral or topical therapies for the periods specified prior to entry into the study: Within 2 days: Topicals of any kind to the selected Treatment Area. Within 2 weeks: Facial topical medications: corticosteroids, alpha- hydroxyacids (e.g., glycolic acid, lactic acid, etc. greater than 5%), beta-hydroxyacid (salicylic acid greater than 2%), urea - greater than 5% or prescription retinoids (e.g., tazarotene, adapalene, tretinoin) to the face and/or anterior scalp. Within 2 weeks: Cryotherapy to lesions adjacent to or within the 25 cm2 Treatment Area. Within 4 weeks: Systemic steroid therapy: chemotherapeutic agents, psoralens, immunotherapy, or retinoids.

Study Objectives This was a multicenter, stratified, open, randomized, comparator-controlled, parallel-group phase III study comparing treatment with Lutathera plus best supportive care (30 mg Octreotide LAR) to treatment with high dose (60 mg) Octreotide LAR in participants with metastasized or locally advanced, inoperable, somatostatin receptor positive, histologically proven midgut carcinoid tumours with progression despite LAR treatment. Conditions: Carcinoid Tumor of the Small Bowel, Neuroendocrine Tumour Intervention / Treatment: DRUG: Octreotide LAR, DRUG: 177Lu-DOTA0-Tyr3-Octreotate Location: Germany, Portugal, Italy, Spain, United Kingdom, United States, Belgium, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Presence of metastasized or locally advanced, inoperable (curative intent) at enrollment time, histologically proven, midgut carcinoid tumour (to be centrally confirmed). * Ki67 index <= 20% (to be centrally confirmed). * Patients on Octreotide LAR at a fixed dose of 20 mg or 30 mg at 3-4 weeks intervals for at least 12 weeks prior to randomization in the study. * Patients >=18 years of age. * Patients must have progressive disease based on RECIST Criteria, Version 1.1 while receiving an uninterrupted fixed dose of Octreotide LAR (20-30 mg/3-4 weeks). Disease progression must be centrally confirmed. In order to make the assessment, two CT (or MRI) scans are required. The oldest scan must not be older than 3 years from the date of randomization. The most recent scan must not be older than 4 weeks from the date of randomization. Both scans must be obtained while the patient is receiving the same fixed dose of Octreotide LAR (20-30 mg/3-4 weeks) with the following exceptions; 1) it is acceptable if the oldest scan is obtained within 12 weeks of the patient receiving a fixed dose regimen of Octreotide LAR (20-30 mg/3-4 weeks); AND 2) it is acceptable for either scan to be obtained before or during the time a patient receiving a fixed dose of Octreotide LAR has switched to an equivalent dose of short acting Octreotide for up to 6 weeks in order to obtain an OctreoScan®, provided the patient returns to the Octreotide LAR fixed dose after the OctreoScan® has been obtained. * Confirmed presence of somatostatin receptors on all target lesions (for target/non-target/measurable lesions definition see §Appendix 2, Section 1 and 2, RECIST Criteria, Version 1.1) documented by CT/MRI scans, based on positive OctreoScan® imaging within 24 weeks prior to randomization in the study (to be centrally confirmed). The OctreoScan® should be one that was performed while the patient was on a fixed dose of Octreotide LAR. If a patient has had an OctreoScan® performed while Octreotide LAR treatment-naïve, the patient must have a repeat OctreoScan® performed after 3 months of Octreotide LAR treatments before entering the clinical study to prove that the index lesions or new lesions still meet the criteria for inclusion. It is acceptable to have patients temporarily switched to Octreotide s.c. (up to six weeks) in order to obtain an OctreoScan®, provided they return to the same fixed dose of Octreotide LAR prior to the scan. * The tumour uptake observed in each target lesion (for target/non-target/measurable lesions definition see §Appendix 2, Sections 1 and 2, RECIST Criteria, Version 1.1) using OctreoScan® must be >= normal liver uptake observed on planar imaging (to be centrally confirmed) (§Appendices 5 and 6). * Karnofsky Performance Score (KPS)>=60. * Presence of at least 1 measurable site of disease. * [Applicable only for France] All patients included in the trial must be affiliated with a social security regime or be a beneficiary of the same in order to be included in the study. Exclusion Criteria: * Either serum creatinine >150 µmol/L (>1.7 mg/dL), or creatinine clearance <50 mL/min calculated by the Cockroft Gault method, eventually confirmed by measured creatinine clearance (or measured glomerular filtration rate (GFR) using plasma clearance methods, not gamma camera-based) <50 mL/min (the measured creatinine clearance / GFR is required only as confirmatory exam). * Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <2x109/L (2000/mm3); platelets <75x109/L (75x103/mm3). * Total bilirubin >3 x ULN. * Serum albumin <3.0 g/dL unless prothrombin time is within the normal range. * Pregnancy or lactation. * For female patients of childbearing potential (defined as < 2 years after last menstruation and not surgically sterile) and male patients, who are not surgically sterile or with female partners of childbearing potential: absence of effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal gel) as defined in §Appendix 7. * Treatment with >30 mg Octreotide LAR at 3-4 weeks intervals within 12 weeks prior to randomization in the study. * Peptide receptor radionuclide therapy (PRRT) at any time prior to randomization in the study. * Any surgery, radioembolization, chemoembolization, chemotherapy and radiofrequency ablation within 12 weeks prior to randomization in the study. * Interferons, Everolimus (mTOR-inhibitors) or other systemic therapies within 4 weeks prior to randomization in the study. * Known brain metastases, unless these metastases have been treated and stabilized for at least 24 weeks, prior to enrollment in the study. Patients with a history of brain metastases must have a head CT with contrast to document stable disease prior to randomization in the study. * Uncontrolled congestive heart failure (NYHA II, III, IV). * Uncontrolled diabetes mellitus as defined by a fasting blood glucose >2 ULN. * Any patient receiving treatment with short-acting Octreotide, which cannot be interrupted for 24 h before and 24 h after the administration of 177Lu-DOTA0-Tyr3-Octreotate, or any patient receiving treatment with Octreotide LAR, which cannot be interrupted for at least 6 weeks before the administration of 177Lu-DOTA0-Tyr3-Octreotate, unless the tumour uptake on target lesions observed by OctreoScan® imaging during continued Octreotide LAR treatment is at least as high as normal liver uptake observed by planar imaging. * Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with the completion of the study. * Prior external beam radiation therapy to more than 25% of the bone marrow. * Current spontaneous urinary incontinence. * Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and proven no evidence of recurrence for 5 years. * Patients who have not provided a signed informed consent form to participate in the study, obtained prior to the start of any protocol related activities. * Patient with known incompatibility to CT Scans with I.V. contrast due to allergic reaction or renal insufficiency. If such a patient can be imaged with MRI, then the patient would not be excluded. * Patients who have participated in any therapeutic clinical study/received any investigational agent within the last 30 days are excluded from participation in this trial.

Study Objectives Recent preclinical studies suggest that combining MEK and MDM2 inhibition synergize to induce apoptosis in RAS/BRAF-mutant and TP53 wild-type CRC models. In vitro, in RKO cell lines (poorly differentiated colon carcinoma cell line resistant to single agent targeting MDM2 and MEK and BRAF inhibition), the MDM2 plus MEK inhibitor combination generated a synergistic increase in apoptotic index. In vivo, in mice harboring human RKO colon tumor xenografts the combination of MDM2 plus MEK inhibition elicited 93% decreases in tumor volume. This trial is to conduct a single-center, Phase 1 dose escalation study of trametinib combined with HDM201 (a HDM2 inhibitor) in patients with advanced/metastatic RAS/RAF mutant and TP53 wt CRC. Conditions: Colorectal Cancer, Advanced Cancer, Metastatic Cancer Intervention / Treatment: DRUG: HDM201, DRUG: Trametinib Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * I1.Adult men and women >= 18 years at time of inform consent form signature. * I2. Patients with histologically confirmed locally advanced or metastatic CRC bearing RAS (may be KRAS or NRAS or HRAS) or BRAF mutation, and TP53 wild type Note : TP53 wt status has to be determined by NGS sequencing of the full coding sequence using a tumor sample collected no longer than 36 months before inclusion. Note: BRAF translocation are eligible. * I3. Previously treated by at least one prior chemotherapy line of treatment in the advanced/metastatic setting. * I4. Documented progressive disease and presence of at least one measurable lesion according to RECIST 1.1 based on screening tumor assessment. * I5.Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale. * I6. Adequate organ function defined according to the following lab tests performed within 7 days before C1D1: Bone marrow (without transfusion within 7 days) :Absolute neutrophil count (ANC) >= 1.5 x 109/L, Hemoglobin >= 9 g/ dL, Platelet count >= 100 x 109/L. Coagulation: INR <= 1.5, aPTT <= 1.5 ULN. Note: patients receiving therapeutic anticoagulation should be on a stable dose for at least 7 days prior to C1D1. Liver function: Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) <=3 ULN (or <= 5.0 ULN in case of liver metastasis or hepatic infiltration), Serum bilirubin <= 1.5 ULN (except for patients with Gilbert disease for whom a total serum bilirubin <= 3 ULN is acceptable). Renal function: Calculated creatinine clearance >= 50 mL/ min/1.73m2 or serum creatinine <=1.5ULN. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), formulae will be used for creatinine clearance calculation. Proteinuria <= +1 on dipstick or <= 1 g/24 hours. * I7.Adequate cardiovascular function QTcF <=470ms, Resting blood pressure systolic <160mmHg and diastolic<100mmHg, LVEF >=50% as determined by transthoracic echocardiogram. * I8.Presence of at least one biopsable lesion i.e. at least one lesion with a diameter >=10 mm, visible by medical imaging and accessible to repeatable percutaneous or endoscopic sampling that permit core needle biopsy without unacceptable risk and suitable for retrieval of a minimum of three, but ideally four, cores using a biopsy needle of at least 16-gauge. Note: RECIST target lesion are not to be biopsied. *I9 Minimal wash out period required for prior treatments (delay from the last dose of the prior treatments to C1D1) : Any investigational drug > 28 days or five half-lives, whichever is longer, Major surgery >21 days, Note: If a patient underwent a major surgical procedure, he/she must have adequately recovered from the toxicity (i.e. wound healing) and/or complications from the intervention prior to starting therapy. Radiotherapy > 28 days, Immunotherapy > 21 days, Chemotherapy > 14 days, Live vaccines > 28 days. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed. Growth factors targeting the myeloid lineage (e.g. GCSF, GM-CSF, M-CSF) > 14 days. * I10 Patients able to swallow orally administered medication and do not have any clinically significant gastrointestinal abnormalities that may alter absorption of study drugs such as malabsorption syndrome or major resection of the stomach or bowels. * I11 Fertile men must agree to use effective contraception from C1D1 until 4 months after the last dose of study drugs. * I12 Women of child-bearing potential must have a negative serum pregnancy test within 7 days of first dose of study drugs and agree to use effective contraception from the date of negative pregnancy test to up to 4 months after the last dose of study drugs. * I13 Patient should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol. * I14 Patients must be covered by a medical insurance. Exclusion Criteria: * E1 Cancer disease considered curable with surgery or radiotherapy. * E2 Prior exposure to HDM2 inhibitors and/or MEK inhibitors. * E3 Presence of persisting AE related to anticancer treatments and Grade >= 2 according to CTCAE V5.0 except alopecia, neuropathy and biological values defined in inclusion criteria. * E4 Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection that requires nutritional support). * E5 Patients with significant active or uncontrolled cardiovascular disease or prior medical cardiac function disorders including for example uncontrolled hypertension, peripheral vascular disease, congestive heart failure (Class III-IV according to New York Heart Association [NYHA] scale), cardiac arrhythmia, or acute coronary syndrome within 6 months of C1D1 or myocardial infarction, angina pectoris, symptomatic pericarditis, within 12 months of C1D1 and patients with drug eluting stents for cardiovascular purposes. * E6 .Patients diagnosed with treatment-related interstitial lung disease or pneumonitis. * E7 Patients with secondary malignancy unless this malignancy is not expected to interfere with the evaluation of study endpoints and is approved by the sponsor. Examples of the latter include :basal or squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, localized prostate cancer, prior malignancy and no evidence of disease for >= 2 years. * E8 Patients requiring the use of the following forbidden concomitant treatments : Any anticancer therapy other than the protocol specified therapies including any investigational agent, any chemotherapy, radiotherapy (except palliative radiotherapy after discussion with the sponsor), immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable. Strong and moderate inducers and inhibitors of CYP3A4/5, Live vaccines, CYP3A4/5 substrates with a narrow therapeutic index: prohibited 24 hours prior and 1 week after HDM201 administration, Substrates of OATP1B1: prohibited 24 hours prior and 48 hours after HDM201 administration. * E9 History or current evidence of Retinal Vein Occlusion (RVO) or central serous retinopathy (CSR) or risk factors including uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes. * E10 Patients with active hemolysis. * E11 Known VIH infection * E12 Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. * E13 Symptomatic CNS metastases. Note: Patients with CNS metastases are eligible only if they are asymptomatic, off corticosteroids, radiographically stable for at least 2 months prior C1D1 and considered not to be at risk of bleeding. * E14 Hypersensitivity to trametinib or HDM201 or any of their excipients. * E15 Pregnant or breast-feeding female patients.

Study Objectives This single center study will help determine the absorption, metabolism, and excretion of LBH589 and to assess the safety and efficacy of LBH589 in advanced cancer patients for whom no standard therapy exists. Conditions: Cancer Patients With Advanced Solid Tumors Including Lymphoma or Chronic Hematological Malignancies Intervention / Treatment: DRUG: LBH589 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 or cytologically confirmed cancer patients including solid tumors, lymphoma, or chronic hematological malignancies with progression on prior standard therapies. * Eastern Cooperative Oncology Group (ECOG) Performance Status of < 2 * Normal renal and hepatic function Exclusion criteria * Patients with central nervous system (CNS) involvement or brain metastases * Patients who have received chemotherapy, any investigational drug, undergone major surgery, or received wide field radiotherapy less than 4 weeks ago * Patients with congenital long QT syndrome or uncontrolled hypertension * Patients with a myocardial infarction or unstable angina within 6 months * Congestive heart failure * Impairment of gastrointestinal (GI) function * Use of any anti-cancer therapy * Female patients who are pregnant or breast feeding Other protocol inclusion/exclusion criteria may apply.

Study Objectives This 2 arm study will compare the efficacy and safety of continuation or discontinuation of Herceptin treatment in combination with 2nd line chemotherapy, in patients with HER2 positive metastatic breast cancer whose condition has progressed on 1st line chemotherapy plus Herceptin. Patients will be randomized either to continue or discontinue Herceptin treatment (2mg/kg iv infusion weekly, or 6mg/kg iv infusion every 3 weeks) while receiving 2nd line chemotherapy of the investigator's choice. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals. Conditions: Breast Cancer Intervention / Treatment: DRUG: trastuzumab, DRUG: Chemotherapy Location: Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * female patients, >=18 years of age; * metastatic breast cancer; * HER2 overexpression (IHC 3+ and/or FISH positive); * disease progression during or after previous 1st line chemotherapy plus Herceptin; * scheduled to receive 2nd line chemotherapy. Exclusion Criteria: * incompatibility with previous Herceptin therapy; * pregnancy.

Study Objectives The study is to observe safety, survival effect and peripheral T-lymphocyte subsets of combination therapy with percutaneous microwave ablation (MWA) and adoptive immunotherapy in hepatocellular carcinoma(HCC). Conditions: Hepatocellular Carcinoma Intervention / Treatment: BIOLOGICAL: adoptive immunotherapy, PROCEDURE: MWA Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2, PHASE3 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * single HCC of 5 cm or smaller; * three or fewer multiple HCC with a maximum dimension of 3 cm or less; * absence of portal vein thrombosis or extrahepatic metastases; * Child-Pugh classification A or B; * tumor accessible via a percutaneous approach. white blood cell count >2 x 109/L, platelet count >40 x 109/L,serum creatinine <110 μmol/L, aspartate aminotransferase <3 times the upper limit, serum bilirubin <2.5 times the upper limit, prothrombin time <19 seconds. Exclusion Criteria: * pregnant or breast-feeding; psychiatric problems, addiction, or any other disorder that prevented informed consent; * active uncontrolled infection; concurrent systemic corticosteroid treatment; * systemic autoimmune disease; * clinically significant ischemic heart disease or cardiac failure; * and chemotherapy or radiotherapy within the preceding 6 months

Study Objectives VEGF inhibition by BEV may induce a change in tumor invasiveness and treatment failure is often associated with remote metastases. BEV may stop the growth of tumor cells by blocking blood flow to the tumor. Cediranib, a pan-VEGF inhibitor has shown promising results in recurrent GBM. VEGF-blocking with small molecules may overcome the mechanism of resistance, and response to BIBF-1120 in such circumstances may open a new treatment option in GBM. In additional, recurrent glioblastomas have an extremely poor prognosis, so innovative therapies are needed. Conditions: Recurrent Glioblastoma Intervention / Treatment: DRUG: BIBF1120 Location: Denmark Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion criteria * Written informed consent * Histological verification of primary GBM and failure after radiotherapy and TMZ - Previously received radiotherapy and TMZ * More than 4 weeks since any of the following prior treatments * Chemotherapy (6 weeks for nitrosureas or mitomycin C) * Radiotherapy to nontarget lesions or lesions that are not to be biopsied * Investigational agents * More than 6 months since prior major surgery or open biopsy and recovered (only 6 weeks required if operation is for recurrent BGM) * ● ECOG performance status 0-1 * Age > 18 years * Creatinine normal OR creatinine clearance >= 60 mL/min * Fertile females must use anticonception (p- pills, IUD, depot injection of gestagen, subdermal * implantation, hormonal vaginal ring or transdermal depot plaster, throughout the study and 3 * months after discontinuation of study drugs. Fertile men must use dobbelt barrier method * (preservative with sperm inhibiting creme) or female partner uses the above mentioned * contraception. * Fertile males must use preservatives. Exclusions criteria * Prior treatment with BIBF 1120 or any other VEGFR inhibitor, except bevacizumab in Group 2 * Chemo-, hormono-, radio-(except for brain and extremities) or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks prior to treatment with the trial drug. * Persistence of clinically relevant therapy related toxicity from previous chemo and/or radiotherapy * Treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial * Therapeutic anticoagulation( except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid<325mg per day * Major injuries within the past 10 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period * History of clinically significant haemorrhagic or thromboembolic event in the past 6 months * Known inherited predisposition to bleeding or thrombosis * Significant cardiovascular diseases ( i.e. uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion) * Proteinuria CTCAE grade 2 or greater * Hepatic function: total bilirubin outside of normal limits; ALT or AST > 1.5 ULN * Coagulation parameters: International normalised ratio ( INR) > 2, prothrombin time - (PT) and partial thromboplastin time (PTT) > 50% of deviation of institutional ULN * Absolute neutrophil count ( ANC) < 1500/ml, platelets < 100000/ml, Haemoglobin < 9.0 g/dl * Other malignancies within the past 5 years other then basal cell skin cancer or carcinoma in situ of the cervix * Active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy * Active or chronic hepatitis C and/or B infection * Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug * Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study. * Pregnancy or breast feeding * Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule * active alcohol or drug abuse

Study Objectives This study is an open-label study. It has two stages. Stage 1 is a dose escalation phase of the study to determine and evaluate the safety and tolerability of repeated treatments with a genetically engineered herpes simplex virus NV1020 administered locoregionally to the liver. Stage 2 is to evaluate the dose found in Stage 1 to be "optimally tolerated". Stage 2 is to assess the efficacy of the optimally tolerated dose of NV1020 by itself and in combination with second-line chemotherapy. Assignment to Stage 1 or Stage 2 of the study is determined by when the patient enters the study. Conditions: Colorectal Cancer, Liver Neoplasms Intervention / Treatment: DRUG: NV1020 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: * Ability to understand and willingness to sign a written informed consent (includes willingness to avoid physical intimacy during and for 2 weeks post NV1020 treatment) * 18 years or more of age * Colorectal adenocarcinoma histologically confirmed within one year prior to enrollment in the study * Liver dominant metastases (CT-measurable lesions with less than 50% total liver involvement), histologically confirmed * Failed conventional chemotherapy for metastatic disease (e.g. tumors no longer responding to 5-FU/leucovorin in combination with irinotecan or oxaliplatin with or without one monoclonal antibody) * Candidate for additional chemotherapy (and/or experimental anti-cancer therapy, if this is the only remaining treatment option) * Karnofsky Performance Status 70% or greater * Life expectancy greater than or equal to 4 months, based on the investigator's opinion * Seropositive for herpes simplex virus-1 (HSV-1) * Fecund females: negative for pregnancy test (urine or serum) * Effective double-barrier contraception for a minimum of 2 months following final infusion of NV1020 Exclusion Criteria: * Dominant extrahepatic disease, including cerebral metastases, significant malignant ascites or other extrahepatic metastases that are symptomatic, in critical locations or otherwise likely to confound NV1020 evaluations, in the opinion of the investigator * Seronegative for HSV-1 * Significant active/unstable non-malignant disease or laboratory test (hematology and chemistry) results that meet any of the following: * White blood cell count (WBC) less than or equal to 3 x 10e3/mm3 * Absolute neutrophil count (ANC) less than or equal to 1.5 x 10e3/mm3 * Platelets less than or equal to 100,000/mm3 * Hemoglobin (Hgb) less than or equal to 9.0 g/dL * Prothrombin time/partial thromboplastin time (PT/PTT) > upper limit of normal (ULN) * Serum creatinine > 2.0 mg/dL * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times ULN or total bilirubin > 1.5 times ULN * Alkaline phosphatase > 2.5 times ULN * Chemotherapy < 4 weeks prior to the first NV1020 infusion (mitomycin or nitrosurea < 6 weeks) * Immunotherapy < 6 weeks prior to the first NV1020 infusion * Radiotherapy (external or internal) to the liver * Major surgery (excluding pump placement and cholecystectomy) <= 2 weeks prior to the first NV1020 infusion but the subject must be clinically stable. Pump placement and cholecystectomy <= 1 week prior to the first NV1020 infusion but the subject must be clinically stable * Female who is pregnant or nursing * Patients wishing to conceive within 2 months after the last infusion of NV1020 * Any investigational agent administered less than or equal to 4 weeks prior to NV1020 infusion * Acute HSV infection requiring systemic antiviral therapy or history of serious HSV infection (e.g., ocular, encephalitic, etc.) * Active viral hepatitis (evidence for infection with hepatitis A, B or C viruses) * Known infection with HIV * Known hypersensitivity to any component of the NV1020 formulation * History of, or current, bleeding or coagulation disorder * History of significant hepatic fibrosis, cirrhosis, or hemachromatosis * History of malignancy other than colorectal cancer, within 5 years prior to start of study participation, with the exception of in situ cervical or skin carcinoma * Active severe infection and any other concurrent disease or medical conditions that are likely to interfere with the study, as judged by the investigator * Systemic corticosteroid administration < 4 weeks prior to starting NV1020 treatment * Prior treatment with NV1020 or other putative oncolytic viruses

Study Objectives The purpose of this study is to understand how patients with mRCC respond to the study medicine (called sunitinib) when they receive it as the first line of treatment after finding out the cause for the disease. This study will look into how different and how well groups of people with high chances of developing the disease respond to the study medicine. All data for this study will be anonymously extracted from data already entered in RCC Registry which is owned by Turkish Oncology Group Association (TOGD). This study will pull out records from the Registry between 01-Mar-2019 and 30-Oct-2022 that belongs to people: * who are Turkish citizens * who are older than 18 years * who were found out to have mRCC * who received sunitinib as the first line treatment after finding out the cause for the disease This study will look at the responses, experiences and how long the patients use the study medicine sunitinib. Conditions: Carcinoma, Renal Cell, Clear-cell Metastatic Renal Cell Carcinoma Intervention / Treatment: DRUG: Sunitinib Location: Turkey Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Being a Turkish citizen. * Being older than 18 years-old. * Being clinically diagnosed with mRCC and treated. * Being treated with Sunitinib in first line Exclusion Criteria: * Patients whose treatment was initiated but excluded from follow-up for any reason.

Study Objectives This is a multicenter, randomized, open label study designed to evaluate the efficacy and safety of prolonged treatment with bortezomib twice monthly and dexamethasone after a salvage treatment containing bortezomib for relapsed or refractory multiple myeloma patients. Conditions: Multiple Myeloma Intervention / Treatment: DRUG: Bortezomib, DRUG: Dexamethasone Location: Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patient is of a legally consenting age as defined by local regulations. * Patient is, in the investigator(s) opinion willing and able to comply with the protocol requirements. * Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care. * Female patient is either post-menopausal for 24 consecutive months or surgically sterilised or agree to continuous abstinence from heterosexual sexual contact or willing to use two acceptable method of birth control at the same time (one highly effective method and one additional effective method) (Highly Effective Methods: Intrauterine device -IUD-; Hormonal -birth control pills, injections, implants-; tubal ligation; partner's vasectomy; Additional Effective Methods: Latex condom; Diaphragm; Cervical Cap) for 4 weeks prior to beginning study drug therapy, during study drug therapy (including dose interruption) and for 4 weeks after discontinuation of therapy. * Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) during study drug therapy (including dose interruption) and for 4 weeks after discontinuation of bortezomib therapy. * Patient was previously diagnosed with multiple myeloma based on standard criteria. * Patient is relapsed or refractory after one to three lines of treatment and the last one must be a bortezomib-containing regimen, without evidence of progressive disease. * Patient had previously received at least 4 cycles of a salvage treatment containing bortezomib, before enrolment, without evidence of progressive disease. * Patient must be enrolled and start therapy within 45 days from the completion of the last salvage cycle containing Bortezomib. * Before the salvage treatment with bortezomib-based regimens, patient must have measurable disease Exclusion Criteria: * Any serious medical condition, laboratory abnormality or psychiatric illness that prevented the subject from signing the informed consent form or placed the subjects at unacceptable risk. * Pregnant or lactating females * Known positive for HIV or active infectious hepatitis type A, B or C * Peripheral neuropathy or neuropathic pain grade 2 or higher, as defined by National Cancer Institute Common Toxicity Criteria (NCI CTC) 4.0 * Infiltrative pulmonary disease.

Study Objectives This 2 arm study will compare the efficacy and safety of continuation or discontinuation of Herceptin treatment in combination with 2nd line chemotherapy, in patients with HER2 positive metastatic breast cancer whose condition has progressed on 1st line chemotherapy plus Herceptin. Patients will be randomized either to continue or discontinue Herceptin treatment (6mg/kg iv infusion every 3 weeks) while receiving second-line chemotherapy of the investigator's choice. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals. Conditions: Breast Cancer Intervention / Treatment: DRUG: Second line chemotherapy, DRUG: trastuzumab [Herceptin] Location: Bulgaria, Hungary, Israel, Estonia, Turkey, Lithuania, Slovakia, Macedonia, The Former Yugoslav Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * female patients, >= 18 years of age; * metastatic breast cancer; * HER2 overexpression (IHC 3+ and/or FISH positive); * disease progression during or after previous 1st line chemotherapy + Herceptin; * scheduled to receive 2nd line chemotherapy. Exclusion Criteria: * concurrent immunotherapy or hormonal therapy; * anthracyclines as part of previous 1st line chemotherapy or planned 2nd line chemotherapy; * cardiac toxicity during previous 1st line chemotherapy + Herceptin; * history of other malignancy within last 5 years.

Study Objectives This was a Phase Ib/II study of the ALK inhibitor ceritinib in combination with the CDK4/6 inhibitor LEE011 in patients with ALK-positive non-small cell lung cancer. The purpose of the study was to determine the MTD/RP2D of the LEE011 and ceritinib combination and evaluate whether the combination was safe and had beneficial effects in ALK-positive advanced non-small cell lung cancer patients. This trial did not progress to Phase II. Trial population terminated before reaching Phase II Conditions: Non-small Cell Lung Cancer Intervention / Treatment: DRUG: Ribociclib, DRUG: Ceritinib Location: Korea, Republic of, Italy, Spain, United States, Taiwan, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patients must be diagnosed with ALK-positive advanced NSCLC. The tumor must be ALK-positive as determined by ALK rearrangement in >=15% of cells (as measured by FISH using the Vysis break-apart ALK probe) or by using the Ventana ALK IHC test. The analysis may be performed locally. * Eastern cooperative oncology group (ECOG) performance status <= 2. * Measurable disease as per RECIST v1.1 * Availability of tumor sample: For ALK inhibitor naïve patients: o A representative tumor sample must be submitted. An archival tumor specimen is acceptable For patients after progression on an ALK inhibitor: o A new tumor biopsy is required unless a biopsy performed after progression on the patient's most recent ALK inhibitor is available for submission For all patients a newly obtained tumor specimen must be submitted if no appropriate archival sample is available. In the event that no sample is available and a new biopsy cannot be obtained, enrollment may be considered after discussion with the sponsor. Exclusion Criteria: * For Phase I part: o Patients who have not previously received at least one line of therapy for ALK-positive NSCLC * For Phase II part: * Group A: prior therapy with any ALK inhibitor is not permitted. * Group B: progression following any ALK inhibitor(s) other than ceritinib is required and the last dose of the ALK inhibitor must be no more than 60 days prior to the first dose of study drug. Prior ceritinib is not permitted. * Group C: progression following ceritinib is required and the last dose of ceritinib must be no more than 60 days prior to the first dose of study drug. * Patients who have previously been unable to tolerate ceritinib, in the opinion of the investigator. Exceptions to this exclusion include nausea, vomiting and diarrhea in patients taking ceritinib under fasted conditions. * Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of steroids or local CNS-directed therapy to control their CNS disease * Patients with abnormal laboratory values during screening and on day 1 of pre-dose * Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of ceritinib or LEE011 * Patients who are currently receiving treatment (that cannot be discontinued at least 1 week prior to the initiation of the study) with agents that are known to be any of the following: strong inducers or inhibitors of CYP3A4/5; sensitive substrates of CYP3A; substrates of CYP3A4/5 or CYP2C9 with a narrow therapeutic index. * Patient has a history of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease. * Patient with impaired cardiac function or any clinically significant uncontrolled cardiac disease, and/or, cardiac repolarization abnormality, including any of the following: Clinically significant heart disease such as CHF requiring treatment (NYH grade >= 2), history of angina pectoris, myocardial infarction, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry, documented cardiomyopathy, or left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition scan (MUGA) or echocardiogram (ECHO). Uncontrolled systolic blood pressure (SBP) >=160 mmHg and/or diastolic blood pressure (DBP) >=100 mmHg, with or without anti-hypertensive medication. Initiation or adjustment of antihypertensive medication (s) is allowed prior to screening, Systolic blood pressure (SBP) <90 mmHg Standard 12-lead ECG values defined as the mean of the triplicate ECGs and assessed by central laboratory * QTcF interval at screening >450 msec (using Fridericia's correction) * Resting heart rate <50 bpm or > 90 bpm Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: * Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia * Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued or replaced by safe alternative medication (e.g. within 5 half-lives or 7 days prior to starting study drug) * Inability to determine the QTcF interval Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block). Other protocol-defined inclusion/exclusion criteria may apply.

Study Objectives This is a single centre prospective biological translational research study involving the collection of tumour tissue, blood samples and clinical data from patients being treated with regorafenib for metastatic Colorectal Cancer (mCRC) at the Royal Marsden Hospital. Patients will be eligible for the study if they have a histological diagnosis of CRC, are refractory to standard available therapies with palliative intent for mCRC, have received prior treatment with at least one anti-VEGF antibody and chemotherapy drugs including fluorouracil (5FU) or capecitabine, oxaliplatin and irinotecan, and patients have RAS mutant tumours. Conditions: Metastatic Colorectal Cancer Intervention / Treatment: DRUG: Regorafenib Location: United Kingdom Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Patients with RAS mutant (MT) metastatic colorectal cancer (mCRC) who have been at least once treated with available therapies including fluoropyrimidine-based chemotherapy, oxaliplatin, irinotecan and an anti-angiogenic agent, except for patients who have not been treated with oxaliplatin due to previous documented peripheral neuropathy in an adjuvant setting or in those patients where disease has progressed within a short time from receiving adjuvant treatment (<12 months). * Eligible to receive regorafenib within the context of PROSPECT-R trial at the Royal Marsden Hospital Exclusion criteria: A patient who meets any of the exclusion criteria will NOT be eligible for randomization. A patient must NOT * have had prior treatment with regorafenib or any other VEGF-targeting kinase inhibitor * have had previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (Noninvasive tumor), Tis (Carcinoma in situ) and T1 (Tumor invades lamina propria)]. * Patients that are participating in another clinical trial involving an investigational medicinal product, unless it is more than 14 days after they have ceased the investigational medicinal product * Patients that are participating in another research study involving tumour tissue biopsies planned to take place during the time that the patient is participating in this study * Have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment * If female and of childbearing potential, be engaged in breast feeding * Be unable to swallow oral tablets (crushing of study treatment tablets is not allowed) * Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 month before the start of study medication (except for adequately treated catheter-related venous thrombosis occurring more than one month before the start of study medication) * Interstitial lung disease with ongoing signs and symptoms at the time of informed consent. * Ongoing infection > Grade 2 NCI Common Toxicity Criterial for Adverse Effects (CTCAE). * Uncontrolled hypertension (Systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg) despite optimal medical management * Have congestive heart failure classified as New York Heart Association Class 2 or higher * Have had unstable angina (angina symptoms at rest) or new-onset angina < 3 months prior to screening * Have had a myocardial infarction < 6 months prior to initiation of study treatment

Study Objectives This phase I/II trial studies the side effects and best dose of leflunomide in treating patients with multiple myeloma that has come back (relapsed) or has not responded to previous treatment (refractory). Leflunomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Conditions: Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma Intervention / Treatment: OTHER: Laboratory Biomarker Analysis, DRUG: Leflunomide, OTHER: Pharmacological Study Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: * All subjects must have the ability to understand and the willingness to sign a written informed consent * Patients must have a life expectancy of > 3 months * Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * Patients must have a diagnosis of multiple myeloma * Serum M-protein >= 0.5 g/dL * Urine M-protein >= 200 mg/24 hr * Serum free light chain >=10 mg/dL provided the free light chain (FLC) ratio is abnormal * 10% plasma cells in bone marrow * Patients must be relapsed or are refractory to at least 3 prior lines of therapy, including both a proteasome inhibitor an immunomodulatory drug (IMiD), and for whom a transplant is not recommended (induction therapy and stem cell transplant +/- maintenance will be considered as one regimen) * At least 2 weeks from prior therapy to time of start of treatment; prior therapy includes steroids (except prednisone or equivalent - up to 10 mg per day is allowed) * Platelet count >= 50,000/uL; platelet transfusions are not allowed within 14 days of platelet assessment * Absolute neutrophil count (ANC) >= 1000/mm^3; growth factor is not permitted within 14 days of neutrophil assessment * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.0 x upper limit of normal (ULN) * Total Bilirubin < 1.5 x ULN * Calculated creatinine clearance (CrCl) >= 30 mL/min per 24 hour urine collection or the Cockcroft-Gault formula * Negative serum or urine beta-human chorionic gonadotropin (B-HCG) test (female patient of childbearing potential* only), to be performed locally within the screening period * Negative for tuberculosis antigen (e.g. T-Spot test) * Negative for hepatitis A, B, or C infection * Adequate pulmonary function as defined by forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) >= 50% of predicted by pulmonary function testing * Agreement by females of childbearing potential* and sexually active males to use an effective method of contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for three months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately * A female of childbearing potential is defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months Exclusion Criteria: * Prior treatment with leflunomide * Current or planned use of other investigational agents, or concurrent biological, chemotherapy, or radiation therapy during the study treatment period * Current or planned growth factor or transfusion support until after initiation of treatment; if growth factor or transfusion support is provided between screening and start of treatment, the participant will no longer be eligible * Prior diagnosis of rheumatoid arthritis * Prior allogenic transplant * Acute active infection requiring systemic therapy within 2 weeks prior to enrollment * Pre-existing liver disease * Known human immunodeficiency virus (HIV) infection * History of allergic reactions attributed to compounds of similar chemical or biologic composition to leflunomide or cholestyramine * Non-hematologic malignancy within the past 3 years aside from the following exceptions: * Adequately treated basal cell or squamous cell skin cancer * Carcinoma in situ of the cervix * Prostate cancer < Gleason grade 6 with a stable prostate specific antigen (PSA) * Successfully treated in situ carcinoma of the breast * Clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or the patient's ability to give informed consent * Pregnant women and women who are lactating; breastfeeding should be discontinued if the mother is enrolled on this study * Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc * NONCOMPLIANCE: Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Study Objectives This phase I trial studies the side effects and best dose of intraperitoneal bortezomib when given together with intraperitoneal carboplatin in treating patients with ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer that is persistent or has come back. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bortezomib may help carboplatin work better by making tumor cells more sensitive to the drug. Infusing bortezomib and carboplatin directly into the abdomen (intraperitoneal) may kill more tumor cells. Conditions: Fallopian Tube Clear Cell Adenocarcinoma, Fallopian Tube Endometrioid Adenocarcinoma, Fallopian Tube Mucinous Adenocarcinoma, Fallopian Tube Serous Adenocarcinoma, Fallopian Tube Transitional Cell Carcinoma, Ovarian Brenner Tumor, Ovarian Clear Cell Adenocarcinoma, Ovarian Clear Cell Cystadenocarcinoma, Ovarian Endometrioid Adenocarcinoma, Ovarian Mucinous Adenocarcinoma, Ovarian Mucinous Cystadenocarcinoma, Ovarian Seromucinous Carcinoma, Ovarian Serous Adenocarcinoma, Ovarian Serous Cystadenocarcinoma, Ovarian Transitional Cell Carcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma, Undifferentiated Fallopian Tube Carcinoma, Undifferentiated Ovarian Carcinoma Intervention / Treatment: DRUG: Bortezomib, DRUG: Carboplatin, OTHER: Laboratory Biomarker Analysis, OTHER: Pharmacological Study 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 recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer; histologic documentation of the original primary tumor is required via the pathology report * Patients with the following histologic epithelial cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's tumor, or adenocarcinoma not otherwise specified (N.O.S) * Patients must have either measurable disease or detectable disease: * Measurable disease will be defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measureable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI * Detectable disease is defined in a patient as one who does not have measurable disease but has at least one of the following conditions: * Baseline values of cancer antigen (CA)-125 at least twice the upper limit of normal * Ascites and/or pleural effusion attributed to tumor * Solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions * In addition, patients are allowed to undergo surgical cytoreduction of relapsed disease as proof of detectable disease at the discretion of their treating physician; if performed to allow participation in this protocol, the operative and pathology reports will be required for submission * Patients must have a Gynecologic Oncology Group (GOG) performance status 0, 1, or 2 * Recovery from effects of recent surgery, radiotherapy, or chemotherapy * Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI]) * Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration; continuation of hormone replacement therapy is permitted * Any other prior therapy directed at the malignant tumor, including biological and immunologic agents, must be discontinued at least three weeks prior to registration * Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included non-cytotoxic therapy, intraperitoneal therapy, consolidation, or extended therapy administered after surgical or non-surgical assessment * Patients are required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease * Patients are allowed to receive, but are not required to receive, two additional cytotoxic regimens for management of recurrent or persistent disease (maximum number of prior cytotoxic regimens including primary therapy is 4); patients are allowed to receive, but are not required to receive, biologic (non-cytotoxic) therapy either alone or as part of the cytotoxic regimens for management of recurrent or persistent disease * Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl, equivalent to the National Cancer Institute (NCI) Common Terminology Criteria (CTCAE) version 4 grade 1 * Platelets greater than or equal to 100,000/mcl * Creatinine less than or equal to institutional upper limit of normal (ULN) * Bilirubin less than or equal to 1.5 x ULN (per the NCI CTCAE version 4 grade 1) * Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) less than or equal to 3 x ULN (per the active version of the NCI CTCAE grade 1) * Alkaline phosphatase less than or equal to 2.5 x ULN (per the NCI CTCAE version 4 grade 1) * Neuropathy (sensory and motor) less than or equal to the NCI CTCAE version 4 grade 1 * Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) * Partial thromboplastin time (PTT) =< 1.5 x ULN (heparin, low molecular weight heparin, or alternative anticoagulants are acceptable) * Patients who have met the pre-entry requirements * An approved informed consent and authorization permitting release of personal health information must be signed by the patient or guardian * Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry and be practicing an effective form of contraception * Patients in this trial may receive ovarian estrogen +/- progestin replacement therapy as indicated at the lowest effective dose(s) for control of menopausal symptoms at any time, but not progestins for management of anorexia while on protocol directed therapy or prior to disease progression Exclusion Criteria: * Patients who have had prior therapy with bortezomib * Patient with a history of other invasive malignancies, with the exceptions of non-melanoma skin cancer and localized breast cancer, are excluded if there is any evidence of other malignancy being present within the last five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy * Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of ovarian cancer are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease * Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of ovarian cancer are excluded * Patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease * Patients with known brain metastases are excluded * History of allergic reactions attributed to carboplatin or compounds of similar chemical or biologic composition to bortezomib including boron or mannitol * Patients with synchronous primary endometrial cancer, or a past history of primary endometrial cancer, are excluded, unless all of the following conditions are met: stage not greater than I-B; no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell or other International Federation of Gynecology and Obstetrics (FIGO) grade 3 lesions * Patients with a history of prior myocardial infarction in the last 12 months or patients with new electrocardiographic evidence of acute ischemia or new conduction abnormalities are ineligible * Uncontrolled concurrent illness including but not limited to ongoing or active infection that requires parenteral antibiotics, acute hepatitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Patients with insulin-dependent diabetes will be excluded * Concomitant medications known to inhibit or induce cytochrome P450, family 3, subfamily A, polypeptide 4 (3A4) are to be avoided

Study Objectives The present investigation is a pilot feasibility study that aims to compare a physical exercise intervention in a face-to-face context (considered state of the art) with a physical exercise intervention in a distance context (online), both supervised, in women, of legal age, physically inactive, breast cancer survivors after primary treatment with curative intent. Before and after the intervention these women will have a physical and functional assessment, as well as a pre-trial cardiopulmonary exercise test, to check if there are safety conditions to participate and also to self tailor the exercise prescription. The prescription follows the ACSM´s exercise guidelines for cancer survivors and will comprise a 8 week combined exercise training, 3 times per week, in which two of them will be supervised and the third session of the week (cardio session) won´t. Chat´s and weekly personal messages, as well as education, will be used to promote retention and exercise adherence. Conditions: Breast Cancer Intervention / Treatment: OTHER: Combined exercise training Location: Portugal Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Women * Over legal age * With diagnosis of breast carcinoma between stages 0 and IIIc * ECOG 0 to 1 * Undergoing primary treatment with curative intent (surgery associated or not, with chemotherapy and / or adjuvant radiotherapy) for at least one month * With follow-up on medical oncology consultation at CHVNG/E * With consent of the attending oncologist for the practice of physical exercise * Non-compliance with current physical activity guidelines recommended by the ACSM (moderate aerobic activity> = 150 min / week or vigorous> = 75 min / week and > = 2 strength training sessions / week) * With cognitive capacity to understand the project proposal Exclusion Criteria: * Severe anaemia seen in the last 3 months (Hb <= 8g / dl) or moderate (Hb> 8 and <= 10 g / dl) symptomatic (sustained tachycardia, exertional dyspnea, chest pain or syncope), * Uncontrolled arterial hypertension (HTN grade 3-4 (CTCAE v.5)) (SAD> = 160mmHg and / or DAD> = 100mmHg) and / or potentially fatal consequences (malignant HTN, transient or permanent neurological deficit or hypertensive crisis) * Uncontrolled diabetes mellitus * Known cardiac or respiratory pathology * Any other contraindication given by the physiatrist and / or assistant surgeon

Study Objectives The goal of this clinical research study is to learn if erlotinib hydrochloride (Tarcevaâ (OSI-774 ) can prevent cancer in the mouth of people with a high risk of developing cancer in the mouth. The safety of this drug will also be studied, as well as the drug's effect on different cells in the body. Conditions: Oral Cancer Intervention / Treatment: DRUG: Erlotinib, DRUG: Placebo Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * Male or female patients with one of the following: (a) loss of heterozygosity (LOH) at 3p14 and/or 9p21 in the oral IEN of patients with a history of curatively treated oral cancer or (b) LOH at 3p14 and/or 9p21 plus at one other chromosomal region in the IEN of patients with no oral cancer history. * Participants must have confirmed diagnosis of oral IEN lesion with LOH. (Note:The initial screening biopsy of oral IEN lesion with LOH must be obtained within 12 months of study enrollment. If initial diagnostic biopsy for LOH is > 3 months prior to study enrollment, investigators may use clinical judgment to order an additional screening biopsy to assess histopathological changes). * Age >= 18 years * ECOG performance status <2 * Participants must have normal organ & marrow function as defined below w/in 30 days of randomization:CBC w/ differential white cell count-acceptable results must include:WBC >3,000ul, hemoglobin>10 g/dl, platelet count > 125,000ul, LFTs-total bilirubin & alkaline phosphatase, AST (SGOT) & ALT (SPGT) all w/in <1.5xULN.Note:At the discretion of the attending physician,participants w/ Gilbert's disease may still be eligible to participate in the event the total bilirubin value is >1.5xULN. Kidney function-serum creatinine< 1.5xULN Chemistry-Sodium & potassium all w/in normal institutional limits. * The effects of the study agent on the developing human fetus are unknown.For this reason,WOCBP & men must agree to use adequate contraception (hormonal or barrier method of birth control;abstinence)prior to study entry& for the duration of active treatment.Neg.serum pregnancy test in WOCBP.Childbearing potential will be defined as women who have had menses w/in the past 12 mths,who have not had tubal ligation or bilateral oophorectomy.Should a woman become pregnant or suspect she is pregnant while participating in this study,she should inform her study physician immediately * Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * Patients with active cancer or any cancer within the previous two years, excluding oral and non-melanoma skin cancer. * Patients with acute intercurrent illness or who have had surgery, radiation therapy, or chemotherapy within the preceding 4 weeks unless they have fully recovered. * Patients with a documented history of coagulopathy and/or those taking warfarin or warfarin-derivative anticoagulants * Women who are pregnant (confirmed by b-HCG if applicable) or breastfeeding * Any medical or psychological condition or any reason that, according to the investigator's judgment, makes the patient unsuitable for participation in the study * Patients who have participated in other experimental therapy studies within 3 months of enrollment to this trial * Patients with a history of inflammatory bowel disease * Patients with a documented history of interstitial lung disease

Study Objectives The purpose of this study is to compare the overall survival of nivolumab versus chemotherapy in subjects with relapsed SCLC. Conditions: Lung Cancer Intervention / Treatment: DRUG: Nivolumab, DRUG: Topotecan, DRUG: Amrubicin Location: Hungary, United States, Greece, Taiwan, Austria, Czechia, France, Poland, Israel, Italy, United Kingdom, Denmark, Russian Federation, Spain, Brazil, Belgium, China, Chile, Norway, Germany, Japan, Korea, Republic of, Romania, Switzerland, Australia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed small cell lung cancer (SCLC) * Subjects with either limited or extensive disease stage at the initial diagnosis * Must have recurrence or progression after platinum-based first-line chemotherapy or chemoradiation therapy for the treatment of limited or extensive disease stage SCLC * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Exclusion Criteria: * Untreated or symptomatic central nervous system (CNS) metastases * Prior therapy with anti-PD-1, anti-PDL1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody * Inadequate hematologic or hepatic function

Study Objectives This study examines whether the addition of decitabine to the standard Flu/TBI conditioning regimen prior to allogeneic stem cell transplantation in poor and very poor risk AML patients, reduces the risk of recurrence of the disease. Because decitabine has hardly any side effects, it will likely have little impact on the occurrence of Graft Versus Host Disease. The investigators are looking for a pre-treatment for transplantation which reduces the chance of recurrence of the disease without involving severe damage to normal tissues. Conditions: Acute Myeloid Leukemia (AML) Intervention / Treatment: DRUG: decitabine Location: Belgium, Netherlands Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients eligible for allogeneic HCT, independent of age * Adult patients of any age with a cytopathologically confirmed diagnosis according to WHO classification of newly diagnosed AML (not APL = AML-M3), de novo AML or secondary AML * in first complete remission (CR1) * Poor risk or very poor risk subgroups * WHO performance status <= 2 * Written informed consent Exclusion Criteria: * Patient not in CR1 * Patients who have senile dementia, mental impairment of any other psychiatric disorder that prohibits the patient from understanding and giving informed consent * Active serious infections like HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) * Patient is unwilling to use contraceptive techniques during and for 12 months following treatment * Female patient who is pregnant or breastfeeding * Active and uncontrolled infections

Study Objectives This phase I trial studies the side effects and the best dose of MLN8237 (alisertib) when given together with paclitaxel albumin-stabilized nanoparticle formulation (nab-paclitaxel) in treating patients with solid malignancies that are metastatic or cannot be removed by surgery. Alisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as nab-paclitaxel work by killing the cells or by stopping them from dividing. Giving alisertib together with nab-paclitaxel may provide a more effective anticancer treatment with fewer side effects. Conditions: Adenocarcinoma, Pancreatic Neoplasms Intervention / Treatment: DRUG: MLN8237, DRUG: nab-Paclitaxel Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patient must have a histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures to not exist or are no longer effective (dose-escalation cohorts only). * Patient must have a histologically or cytologically confirmed diagnosis of pancreatic cancer or poorly differentiated neuroendocrine tumor and must have been treated with a regimen with known benefit for pancreatic cancer or poorly differentiated neuroendocrine tumor (MTD expansion cohort only). * Patient must have measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with CT scan, >= 20 mm by chest x-ray, or >= 10 mm with calipers by clinical exam. * Patient must have disease that is easily accessible for a core biopsy as determined by the treating physician or study PI. Patient must agree to the mandatory biopsies at baseline and end of Cycle 2 (MTD expansion cohort only, and at the discretion of the PI/PI optional). * Patient must be >= 18 years of age. * Patient must have an ECOG performance status of 0 or 1 * Patient must have normal bone marrow and organ function as defined below: * Leukocytes >= 3,000/mcL * Absolute neutrophil count >= 1,500/mcL * Platelets >= 100,000/mcL * Hemoglobin > 9.0 g/dL * Total bilirubin <= institutional ULN * AST and ALT < 1.5 x ULN (or < 5 x ULN if known liver metastases) * Calculated creatinine clearance must be > 40 mL/min (by Cockcroft-Gault) * If a female of childbearing potential (defined as a female who is non-menopausal or surgically sterilized), patient must be willing to use an acceptable method of birth control (i.e., hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. If a male with a partner who is a female of childbearing potential, patient must agree to use an acceptable method of contraception during the entire study treatment period through 4 months after the last dose of MLN8237. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. * Patient must be able to take oral medication and to maintain a fast as required for 2 hours before and 1 hour after MLN8237 administration. * Patient (or legally authorized representative if applicable) must be able to understand and willing to sign an IRB approved written informed consent document. Exclusion Criteria: * Patient must not have received chemotherapy or radiotherapy <= 4 weeks or 5 half-lives prior to study entry. * Patient must not have had radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%. * Patient must not have a history of other malignancy <= 2 years previous with the exception of basal cell or squamous cell carcinoma of the skin which was treated with local resection only, an in situ malignancy, or low-risk prostate cancer after curative therapy. * Patient must not have had a prior allogeneic bone marrow or organ transplantation. * Patient must not have previously received nab-paclitaxel. * Patient must not have received any other investigational agents within 14 days prior to study enrollment. * Patient must not have known brain metastases. Patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. * Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to either MLN8237 or nab-paclitaxel, or other agents used in the study. * Patient must not have been treated with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine, or Phenobarbital, or rifampin, rifabutin, rifapentine, or St. John's wort within 14 days prior to the first dose of MLN8237. * Patient must not have received any previous treatment with any Aurora-kinase inhibitors (MTD expansion cohort only). * Patient must not have a history of gastric resection (MTD expansion cohort only). * Patient must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements. * Patient must not have >= grade 2 peripheral neuropathy within 14 days before enrollment. * Patient must not have a known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease. * Patient must not have a requirement for supplemental oxygen. * Patient must not require constant administration of a proton pump inhibitor, H2 antagonist, or pancreatic enzymes. Intermittent uses of antacids or H2 antagonists are allowed. * Patient must not have QTc > 500ms within 14 days before enrollment. * Patient must not have had a myocardial infarction within 6 months prior to enrollment or have 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. * Patient must not be pregnant and/or breastfeeding. * Patient must not be known to be HIV-positive on combination antiretroviral because of the potential for pharmacokinetic interactions with MLN8237 or Abraxane. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated. Inclusion of Women and Minorities Both men and women and members of all races and ethnic groups are eligible for this trial.

Study Objectives This research study is being done to compare the safety and effectiveness of GDC 695 (test drug) against the currently marketed reference drug (diclofenac sodium gel, 3%) and to establish that these two drugs work better than placebo in the treatment of actinic keratosis. Conditions: Actinic Keratosis Intervention / Treatment: DRUG: GDC 695, DRUG: Diclofenac Sodium Gel, 3%, DRUG: Vehicle gel Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Has provided written informed consent. * Immunocompetent male and/or non-pregnant female, 18 years of age or older. * Willing and able to apply the test article(s) as directed, comply with study instructions, and commit to all follow-up visits for the duration of the study. * Clinical diagnosis of actinic keratosis. * In good general health and free of any disease state or physical condition. * Women, must be post-menopausal, surgically sterile, or use an effective method of birth control with a negative urine pregnancy test (UPT) at the Baseline Visit (Day 1). Exclusion Criteria: * Women who are pregnant, breastfeeding, or are planning to become pregnant or breastfeed during the study. * Is currently enrolled in another investigational drug or device study or has used an investigational drug or investigational device within 30 days prior to the Baseline Visit (Day 1). * Has the need or plans to be exposed to artificial tanning devices or excessive sunlight during the study. * Is immunosuppressed (e.g., human immunodeficiency virus [ HIV], systemic malignancy, graft host disease, etc.) or is taking medications that suppress the immune system. * Has experienced an unsuccessful outcome from previous topical diclofenac sodium therapy. * Has a history of sensitivity to any of the ingredients in the test articles or other excipients in the test or reference drug. * Has signs or symptoms consistent with the aspirin (ASA) triad. * Has used topical medications: corticosteroids, alpha hydroxy acids (e.g., glycolic acid, lactic acid, etc. >5%), beta hydroxy acid (salicylic acid >2%), urea >2%, 5-fluorouracil, diclofenac, imiquimod, ingenol mebutate, aminolevulinic acid (ALA) or prescription retinoids (e.g., tazarotene, adapalene, tretinoin), over-the-counter (OTC) products labeled as scrubs of any kind which are used to smooth the skin (as they contain some form of exfoliant such as nut shells, coffee grounds, polymer particles, etc.) within the selected treatment area (face or bald scalp) within one month prior to the Baseline Visit. * Has had cryodestruction or chemodestruction, curettage, photodynamic therapy (PDT), surgical excision, or other treatments for AK within the selected treatment area (face or bald scalp) within one month prior to the Baseline Visit. * Has used oral corticosteroid therapy, interferon, cytotoxic drugs, immunomodulators, immunosuppressive therapies, or retinoids within one month prior to the Baseline Visit. * Has used oral isotretinoin within six months prior to the Baseline Visit. * Has used chemical peels, including but not limited to alphahydroxy acid, betahydroxy acid, bichloroacetic acid, trichloroacetic acid, and phenol within the selected treatment area (face or bald scalp) within six months prior to the Baseline Visit. * Has had dermatologic procedures or surgeries such as: laser resurfacing, PUVA (Psoralen + ultraviolet A) therapy, ultraviolet B (UVB) therapy, ALA-PDT, or dermabrasion within the selected treatment area (face or bald scalp) within six months prior to the Baseline Visit. * Has lesions suspicious for skin cancer (skin cancer not ruled out by biopsy) or untreated skin cancers within the selected treatment area (face or bald scalp). * Has active gastrointestinal ulceration or bleeding or has a history of gastrointestinal bleeds due to use of aspirin or other NSAIDs. * Has severe renal or hepatic impairment. * Has any condition which, in the investigator's opinion, could interfere with the evaluation of the test drugs or that could make it unsafe or preclude the subject's ability to fully participate in this research study.

Study Objectives This study is being done to see if people with Non-Small Cell Lung Cancer (NSCLC) or ovarian cancer benefit from continued treatment with the study drug, RXDX-105. Conditions: Non Small Cell Lung Cancer, Ovarian Cancer, RET Gene Mutation, BRAF Gene Mutation Intervention / Treatment: DRUG: RXDX-105 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: * This individual patient protocol includes treatment for 3 patients previously enrolled on IRB #15-270 (phase1/1b clinical trial RXDX-105-01): Exclusion Criteria: * Any patients other than those described above are excluded.

Study Objectives The purpose of this study is to compare the antitumor activity of everolimus plus best supportive care versus placebo plus best supportive care in patients with progressive nonfunctional neuroendocrine tumor (NET) of gastrointestinal (GI) or lung origin without a history of, or current symptoms of carcinoid syndrome. Conditions: Advanced NET of GI Origin, Advanced NET of Lung Origin, Neuroendocrine Tumors Intervention / Treatment: DRUG: Everolimus, DRUG: Placebo, OTHER: Best suportive care (BSC) Location: Hungary, Canada, Turkey, United States, Greece, Colombia, Taiwan, Austria, Czechia, Poland, Thailand, Italy, Netherlands, United Kingdom, South Africa, Russian Federation, Spain, Lebanon, Belgium, Saudi Arabia, China, Germany, Japan, Korea, Republic of, Slovakia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Pathologically confirmed, well differentiated (G1 or G2), advanced (unresectable or metastatic), neuroendocrine tumor of GI or lung origin * No history of and no active symptoms related to carcinoid syndrome * In addition to treatment-naive patients, patients previously treated with SSA, Interferon (IFN), one prior line of chemotherapy, and/or PRRT were allowed into the study. Pretreated patients had to have progressed on or after the last treatment * Radiological documented disease progression within 6 months prior to randomization * Measurable disease * WHO performance status <=1 * Adequate bone marrow, liver and renal function Exclusion Criteria: * Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, pancreatic islet cell carcinoma, insulinoma, glucagonoma, gastrinoma, goblet cell carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma * Patients with pancreatic NET or NET of origins other than GI or Lung * Patients with history of or active symptoms of carcinoid syndrome (e.g. flushing, diarrhea) * Patients with more than one line of prior chemotherapy * Prior targeted therapy * Hepatic intra-arterial embolization within the last 6 months. Cryoablation or radiofrequency ablation of hepatic metastases within 2 months of randomization * Prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, deforolimus) * Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus) * 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 who had any severe and/or uncontrolled medical conditions such as: * unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction <=6 months prior to randomization, serious uncontrolled cardiac arrhythmia * active 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) * Chronic treatment with corticosteroids or other immunosuppressive agents * Known history of HIV seropositivity * Pregnant or nursing (lactating) women Other protocol-defined inclusion/exclusion criteria might apply.

Study Objectives This randomized phase II trial studies how well lower-dose compared to standard dose regorafenib works in treating patients with colorectal cancer that has spread from the primary site (place where it started) to other places in the body and does not respond to treatment. Regorafenib may stop the growth of colorectal cancer by blocking the growth of new blood vessels necessary for tumor growth and by blocking some of the enzymes needed for cell growth. It is not yet known whether lower-dose or standard dose regorafenib is more effective in treating patients with colorectal cancer. Clobetasol propionate is a steroid cream that is commonly used to treat a variety of skin conditions and may help prevent hand-foot skin reactions in patients receiving regorafenib. Conditions: Colon Adenocarcinoma, Rectal Adenocarcinoma, Stage III Colorectal Cancer AJCC v7, Stage IIIA Colorectal Cancer AJCC v7, Stage IIIB Colorectal Cancer AJCC v7, Stage IIIC Colorectal Cancer AJCC v7, Stage IV Colorectal Cancer AJCC v7, Stage IVA Colorectal Cancer AJCC v7, Stage IVB Colorectal Cancer AJCC v7 Intervention / Treatment: DRUG: Clobetasol Propionate, OTHER: Pharmacological Study, OTHER: Quality-of-Life Assessment, DRUG: Regorafenib Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histological or cytological documentation of adenocarcinoma of the colon or rectum * Advanced or metastatic colorectal cancer with no curative options available and progression on previous standard therapy, including an EGFR inhibitor if KRAS wild-type * Measurable or non-measurable disease * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 * Life expectancy of >= 3 months * Absolute neutrophil count (ANC) > 1500/mm^3 (obtained =< 7 days prior to randomization) * Platelet count > 100,000/mm^3 (obtained =< 7 days prior to randomization) * Hemoglobin > 9.0 g/dL (obtained =< 7 days prior to randomization) * Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 7 days prior to randomization) * Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer) (obtained =< 7 days prior to randomization) * Serum creatinine =< 1.5 x ULN (obtained =< 7 days prior to randomization) * International normalized ratio (INR)/partial thromboplastin time (PTT) =< 1.5 x ULN (obtained =< 7 days prior to randomization) * NOTE: patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists; close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care * Alkaline phosphatase limit =< 2.5 x ULN (=< 5 x ULN for patients with liver involvement of their cancer) (obtained =< 7 days prior to randomization) * Negative serum pregnancy test done =< 7 days prior to randomization, for women of childbearing potential only; note: post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test; the definition of adequate contraception will be based on the judgment of the investigator * Ability to complete questionnaire(s) by themselves or with assistance * Provide informed written consent * Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study) * Willing to provide blood samples for correlative research and banking purposes Exclusion Criteria: * Prior treatment with regorafenib * Major surgical procedure, open biopsy, or significant traumatic injury =< 28 days prior to randomization * Congestive heart failure > New York Heart Association (NYHA) class 2 * Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months) or myocardial infarction less than 6 months prior to randomization * Cardiac arrhythmias requiring anti-arrhythmic therapy; Note: pace makers, beta blockers, or digoxin are permitted * Uncontrolled hypertension; (systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg despite optimal medical management) * History of or current pheochromocytoma * Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism =< 6 months prior to randomization * Ongoing infection > grade 2 National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 * Known history of chronic hepatitis B or C * Patients with seizure disorder requiring medication * Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of randomization and is clinically stable with respect to the tumor at the time of randomization; note: patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies) * History of organ allograft (including corneal transplant) * Evidence or history of bleeding diathesis or any hemorrhage or bleeding event > CTCAE grade 3 =< 4 weeks prior to randomization * Non-healing wound, ulcer, or bone fracture * Renal failure requiring hematological (hemo-) or peritoneal dialysis * Dehydration CTCAE (version 4.0) grade >= 1 * Substance abuse, medical, psychological or social conditions that may interfere with the patient?s participation in the study or evaluation of the study results * Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation * Interstitial lung disease with ongoing signs and symptoms at the time of informed consent * Persistent proteinuria of Common Toxicity Criteria (CTC) grade 3 or higher (>= 3.5 g/24 hours [hrs]) * Patients unable to swallow oral medications * Any malabsorption condition * Unresolved toxicity greater than CTCAE (version 4.0) grade 1 attributed to any prior therapy/procedure excluding alopecia and oxaliplatin induced neurotoxicity =< grade 2 * Albumin levels < 2.5 g/dl * Any of the following: * Pregnant women * Nursing women * Men or women of childbearing potential who are unwilling to employ adequate contraception * NOTE: men and women of childbearing potential must agree to use adequate contraception beginning at the signing of the informed consent form (ICF) until at least 3 months 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 * Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens * Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial * Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm * Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 3 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria]); note: all cancer treatments for cancers that were distinct in a primary site other than colorectal must be completed at least 3 years prior to randomization (i.e., signature date of the informed consent form) * Pleural effusion or ascites that causes respiratory compromise (>= CTCAE version 4.0 grade 2 dyspnea) * Concurrent anti-cancer therapy =< 4 weeks from registration (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) * Current use of clobetasol propionate * Use of any herbal remedy (e.g. St. John?s wort [Hypericum perforatum]) * Patients unable to ambulate or who have amputations or paralysis of any extremity * History of contact dermatitis to clobetasol propionate or similarly fluorinated steroids or other steroids with the propionate ester

Study Objectives The purpose of this research study is to address the challenge of medication management for older patients undergoing treatment for cancer. The sponsor of this protocol is the Massachusetts General Hospital Cancer Center who is providing funding for this research study. Conditions: Breast Cancer, Lung Cancer, GI Cancer Intervention / Treatment: OTHER: Pharmacy Intervention, OTHER: Usual Care Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Age >= 65 years * Diagnosed with any stage breast, GI or lung cancer * Panning to receive first-line chemotherapy at MGH * Verbal fluency in English Exclusion Criteria: * Unwilling or unable to participate in the study * Significant psychiatric, cognitive or other comorbid disease which the treating clinician believes prohibits informed consent or participation in the study

Study Objectives To determine efficacy and safety of Sipjeondaebo-tang for Cancer patients suffering from anorexia after chemotherapy. Sipjeondaebo-tang will be administered for 4 weeks, 3 times per day after a meal. Changes of FAACT scale, Anorexia VAS, Weight, BMI, Clinical laboratory test such as ACTH, Cortisol, Chrelin, IL-6, ESR, CRP will be measured and analyzed. Conditions: Cancer-related Problem/Condition Intervention / Treatment: DRUG: SJDBT, DRUG: Placebo Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * Men and women ages 20 to 80 years * Individuals who are suffering from cancer-associated anorexia * Patients within 1 month after completion of chemotherapy * No plan for additional chemotherapy or radiotherapy * Anorexia visual analogue scale (VAS) >= 40/100mm * Qi deficiency scale >= 30 or Blood deficiency scale >= 30 * Neutrophil >= 1,500/㎕, platelet >= 100,000/㎕ * Total bilirubin lower than upper limit of normal (1.2 mg/㎗) * ALT, AST lower than 2-fold the upper limit of normal * Creatinine lower than 1.5 fold the upper limit of normal(1.09 mg/㎗) * Written informed consent for participation in the trial Exclusion Criteria: * Patient impossible to oral intake * Patient 5 years after cancer diagnosis * ECOG performance status score > 3 * Patient with dementia, delirium, depression * Patient who complain of more than 7 points when we use Numeric Rating Scale, which can affect appetite or calorie intake, within 2 weeks of screening * Patient with diseases which can influence on appetite (such as hypoadrenalism, etc) * Patient who are taking appetizers (such as megestrol acetate, corticosteroids, thalidomide) * Women who has possibility of a pregnancy * Others who are judged not to be appropriate to study

Study Objectives Based on success in other diseases, the Fred Hutchinson Cancer Research Center (FHCRC) has developed a transplant procedure for Fanconi anemia (FA), which does not completely destroy the patient's remaining bone marrow. It should also be less harmful (toxic). Researchers wish to test whether this approach can overcome the graft failure often seen when bone marrow or peripheral blood stem cells from an unrelated donor are used. Researchers also will look at whether the procedure is less toxic than a conventional bone marrow transplant (BMT). Conditions: Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Childhood Acute Myeloid Leukemia in Remission, Childhood Myelodysplastic Syndromes, Fanconi Anemia, Previously Treated Myelodysplastic Syndromes Intervention / Treatment: DRUG: fludarabine phosphate, DRUG: cyclosporine, RADIATION: total-body irradiation, PROCEDURE: allogeneic bone marrow transplantation, PROCEDURE: allogeneic hematopoietic stem cell transplantation, PROCEDURE: peripheral blood stem cell transplantation, DRUG: mycophenolate mofetil 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: * Any patient with marrow failure and increased chromosome fragility as determined in the diepoxybutane (DEB) or mitomycin C test * Any patient with Fanconi anemia (FA) with marrow failure meeting the following criteria: * Granulocyte count < 0.2 x 10^9/L * Platelet count < 20 x 10^9/L * Hemoglobin < 8 g/dl * Corrected reticulocyte count <1% * Any patient with FA as determined by DEB fragility, who has life-threatening marrow failure involving a single hematopoietic lineage * Any patient with FA and pre-existing cytogenetic abnormality including hematopoietic malignancy (myelodysplastic syndromes [MDS] or acute myeloid leukemia [AML]) in remission * DONOR: Unrelated Donors who are prospectively: Matched for human lymphocyte antigen (HLA)-DRB1 and DQB1 alleles (must be defined by high resolution typing); only a single allele disparity will be allowed for HLA -A, B, or C as defined by high resolution typing * DONOR: HLA typing will be performed at the highest level of resolution available at the time of transplant Exclusion Criteria: * Evidence for hematopoietic malignancy in relapse * Heart or lung disease that would prevent compliance with conditioning and GvHD regimen or would severely limit the probability of survival * Human immunodeficiency virus (HIV) seropositive patients * Females who are pregnant or breastfeeding, or unwilling to use contraceptive techniques during and for the 12 months following treatment * DONOR: Donors who by DEB testing are found to have FA * DONOR: Donors who test positive in the lymphocytotoxic crossmatch assay * DONOR: Donors who are HIV positive * DONOR: Donors who for other medical or psychological reasons are not suitable as donors

Study Objectives This phase I trial is studying the side effects of gefitinib in treating patients with metastatic or unresectable head and neck cancer or non-small cell lung cancer. Gefitinib may stop the growth of cancer cells by blocking the enzymes necessary for their growth Conditions: Anaplastic Thyroid Cancer, Insular Thyroid Cancer, Metastatic Parathyroid Cancer, Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Basal Cell Carcinoma of the Lip, Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Recurrent Lymphoepithelioma of the Nasopharynx, Recurrent Lymphoepithelioma of the Oropharynx, Recurrent Metastatic Squamous Neck Cancer With Occult Primary, Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Recurrent Mucoepidermoid Carcinoma of the Oral Cavity, Recurrent Non-small Cell Lung Cancer, Recurrent Parathyroid Cancer, Recurrent Salivary Gland Cancer, Recurrent Squamous Cell Carcinoma of the Hypopharynx, Recurrent Squamous Cell Carcinoma of the Larynx, Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity, Recurrent Squamous Cell Carcinoma of the Nasopharynx, Recurrent Squamous Cell Carcinoma of the Oropharynx, Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Recurrent Thyroid Cancer, Recurrent Verrucous Carcinoma of the Larynx, Stage III Follicular Thyroid Cancer, Stage III Papillary Thyroid Cancer, Stage III Salivary Gland Cancer, Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx, Stage III Verrucous Carcinoma of the Larynx, Stage IIIB Non-small Cell Lung Cancer, Stage IV Lymphoepithelioma of the Nasopharynx, Stage IV Non-small Cell Lung Cancer, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity, Stage IVA Basal Cell Carcinoma of the Lip, Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage IVA Follicular Thyroid Cancer, Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage IVA Lymphoepithelioma of the Oropharynx, Stage IVA Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage IVA Mucoepidermoid Carcinoma of the Oral Cavity, Stage IVA Papillary Thyroid Cancer, Stage IVA Salivary Gland Cancer, Stage IVA Squamous Cell Carcinoma of the Larynx, Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVA Squamous Cell Carcinoma of the Oropharynx, Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVA Verrucous Carcinoma of the Larynx, Stage IVA Verrucous Carcinoma of the Oral Cavity, Stage IVB Adenoid Cystic Carcinoma of the Oral Cavity, Stage IVB Basal Cell Carcinoma of the Lip, Stage IVB Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage IVB Follicular Thyroid Cancer, Stage IVB Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage IVB Lymphoepithelioma of the Oropharynx, Stage IVB Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage IVB Mucoepidermoid Carcinoma of the Oral Cavity, Stage IVB Papillary Thyroid Cancer, Stage IVB Salivary Gland Cancer, Stage IVB Squamous Cell Carcinoma of the Larynx, Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVB Squamous Cell Carcinoma of the Oropharynx, Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVB Verrucous Carcinoma of the Larynx, Stage IVB Verrucous Carcinoma of the Oral Cavity, Stage IVC Adenoid Cystic Carcinoma of the Oral Cavity, Stage IVC Basal Cell Carcinoma of the Lip, Stage IVC Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage IVC Follicular Thyroid Cancer, Stage IVC Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage IVC Lymphoepithelioma of the Oropharynx, Stage IVC Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage IVC Mucoepidermoid Carcinoma of the Oral Cavity, Stage IVC Papillary Thyroid Cancer, Stage IVC Salivary Gland Cancer, Stage IVC Squamous Cell Carcinoma of the Larynx, Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVC Squamous Cell Carcinoma of the Oropharynx, Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVC Verrucous Carcinoma of the Larynx, Stage IVC Verrucous Carcinoma of the Oral Cavity, Thryoid Gland Nonmedullary Carcinoma, Thyroid Gland Medullary Carcinoma, Tongue Cancer, Untreated Metastatic Squamous Neck Cancer With Occult Primary Intervention / Treatment: DRUG: gefitinib Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must have histologically or cytologically confirmed head and neck carcinoma or non-small cell lung cancer which is metastatic or unresectable for which standard curative or palliative measures do not exist or are no longer effective or are likely to be as effective as ZD1839; patients with known brain metastases are only eligible if their brain metastases have been treated and if in the opinion of the treating physician they are stable * Patients must be >= 75 years, or 50 years of age or younger * Serum creatinine =< the institutional upper limit of normal * Bilirubin =< the institutional upper limit of normal * SGOT or SGPT =< 2.5 x the institutional upper limit of normal; SGOT and SGPT could be =< 5 x the upper limit of normal if the patient has liver metastases as long as the bilirubin is normal * AGC of >= 1,500/ul * Platelet count of >= 100,000/ul * Patients requiring agents that induce CYP3A4 are excluded from the study, at the present time, agents known to induce CYP3A4 include the antibiotics nafcillin and rifampin, the anticonvulsants carbamazepine, phenobarbital, phenytoin, oxcarbazepine, fosphenytoin and primidone as well as St. John's Wort, rifabutin, rifapentine and modafinil * Patients may or may not have received prior chemotherapy; patients must not have a curative option and in the opinion of the treating physician there is no other treatment option likely to provide greater benefit; patients must not have received prior treatment with EGFR inhibitors; patients must have recovered from the effects of prior therapy; all prior therapies must be documented * Patients must have a performance status of 0-2 by Zubrod standards * Patients must not be planning to receive concurrent radiation therapy, hormone therapy, chemotherapy or immune therapy for malignancy while receiving protocol treatment * Patients must agree to undergo pharmacokinetic sampling and sample submission * Patients known to be HIV positive and receiving retroviral therapies are not eligible * Patients with any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac or infection) are not eligible * Patients must be able to swallow oral medication in pill form; patients may not receive study medication through a feeding tube * A baseline slit lamp examination is NOT required; however, patients with eye symptoms (eye pain, tearing, redness, vision problems) or known eye disorders should be evaluated by an ophthalmologist/optometrist prior to registration and the results documented on the toxicity form in the notes section * Patients must not be pregnant or nursing; patients of reproductive potential must have agreed to use an effective contraceptive method * If day 28 or 42 falls on a weekend or holiday, the limit may be extended to the next working day * 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 guidelines * All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines * At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base

Study Objectives The purpose of this study is to evaluate both enzastaurin and bevacizumab in the treatment of recurrent malignant gliomas. Conditions: Recurrent Glioblastoma Intervention / Treatment: DRUG: enzastaurin, DRUG: bevacizumab, DRUG: Enzyme-inducing antiepileptic drugs (EIAED), DRUG: Non-enzyme inducing antiepileptic drugs (NEIAED) 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: * Participant must be at least 18 years old * Participant must have been diagnosed with a recurrent brain tumor by magnetic resonance imaging (MRI) scan * Participant must be willing to practice adequate contraception * Participant must be able to swallow the enzastaurin tablets whole and receive bevacizumab intravenously * Participant must agree to use the study drug only as instructed by your study doctor and staff. Exclusion Criteria: * Women who are pregnant or breastfeeding * Participants who have significant heart, liver, kidney, or psychiatric disease * Participants who have an active infection * Participants who have any recent bleeding in the brain * Participants who are taking any anti-coagulation or anti-platelet medication [including aspirin, non-steroidal anti-inflammatories, Cyclooxygenase-2 (COX-2) inhibitors]

Study Objectives This study will find out if trastuzumab deruxtecan is safe and works for participants with gastric or gastroesophageal junction cancer. They must have human epidermal growth factor receptor 2 (HER2)-positive gastric or gastro-esophageal junction (GEJ) cancer: * that cannot be removed surgically * that has moved to other parts of the body * that got worse during or after treatment that included trastuzumab The study will enroll about 80 participants. Sites will be in North America and the European Union. Conditions: Adenocarcinoma Gastric Stage IV With Metastases, Adenocarcinoma - GEJ Intervention / Treatment: DRUG: Trastuzumab deruxtecan Location: Italy, Spain, United Kingdom, United States, Belgium Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Men or women >=18 years old (local regulatory guidelines apply) * Has pathologically documented HER2-positive gastric or GEJ cancer that is unresectable or metastatic, and that progressed during or after treatment regimen containing trastuzumab * Has at least one measurable lesion per RECIST v1.1, as confirmed by investigator review * If of reproductive potential, agrees to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 7 months for females and 4 months for males after the last dose of study drug Exclusion Criteria: * Has had anticancer therapy after first-line treatment regimen containing trastuzumab * Has uncontrolled cardiovascular disease, including any of the following: history of myocardial infarction (MI) within 6 months of first dose or symptomatic congestive heart failure (New York Heart Association Class II to IV), troponin levels consistent with MI as defined according to the manufacturer within 28 days of first dose, or corrected QT interval (QTc) prolongation to >470 ms (females) or >450 ms (male) based on screening triplicate 12-lead electrocardiogram (ECG) * Has history of non-infectious interstitial lung disease (ILD)/pneumonitis that required corticosteroid therapy, or current ILD/pneumonitis that cannot be ruled out at screening * Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of the first dose, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy. * Has pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART) * Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms (Note: participants with clinically inactive brain metastases may be included in the study as well as participants with treated brain metastases who are no longer symptomatic and no longer require treatment with corticosteroids or anticonvulsants.

Study Objectives This is an exploratory study to compare activity and safety in 400 patients with previously untreated metastatic carcinoma of the colon treated with UFOX (a combination regimen of UFT® (Tegafur plus Uracil), Oxaliplatin, Folinic Acid) plus Cetuximab or FOLFOX-4 (a combination regimen of 5 Fluorouracil (5-FU), Oxaliplatin and Folinic Acid) plus Cetuximab) Conditions: Previously Untreated Metastatic Colorectal Cancer Intervention / Treatment: DRUG: UFOX + Cetuximab, DRUG: FOLFOX4 + Cetuximab Location: Israel, Mexico, Germany, Thailand, Italy, Brazil, Australia, Belgium, Greece, Hong Kong, Austria, Argentina, France, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria * Signed written informed consent * Inpatient or outpatient >= 18 years of age * Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum * First occurrence of metastatic disease (not curatively resectable) * Presence of at least one lesion measurable uni dimensionally by computerised tomography (CT) scan or magnetic resonance imaging (MRI). (Target lesion(s) must not lie within an irradiated area) * Life expectancy of >= 3 months * Karnofsky performance status of >= 60, at study entry * White blood cell count (WBC) >= 3 x 10^9/L, with neutrophils >= 1.5 x 10^9/L, platelets >= 100 x 10^9/L, and hemoglobin >= 9 g/dL * Aspartate transaminase and alanine transaminase <= 2.5 x Upper Limit of Normal (ULN) (<= 5 x ULN if liver metastasis are present) * Normal serum creatinine (in case of elevated creatinine, labelled ethylenediaminetetraacetic acid clearance >= 65 mL/min is acceptable) * Effective contraception for both male and female subjects if the risk of conception exists * Tumor biopsy or archived sample available Exclusion criteria: * Brain metastasis and/or leptomeningeal disease (known or suspected) * Previous chemotherapy for colorectal cancer except adjuvant treatment with progression of disease documented > 6 months after end of adjuvant treatment. * Previous oxaliplatin-based chemotherapy * Surgery (excluding diagnostic biopsy) or irradiation within 4 weeks prior to randomization * Concurrent or previous chronic systemic immune therapy, targeted therapy, anti-vascular epithelial growth factor (VEGF) therapy, epidermal growth factor receptor (EGFR) pathway targeting therapy not indicated in the study protocol * Concurrent hormonal therapy not indicated in the study protocol except for physiologic replacement or contraception * Clinically relevant coronary artery disease, history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia * Peripheral neuropathy >grade 1 * Known hypersensitivity reaction to any of the components of the treatment. * Any concurrent malignancy other than basal cell cancer of the skin, or pre-invasive cancer of the cervix. (Subjects with a previous malignancy but without evidence of disease for >= 5 years will be allowed to enter the study) * Pregnancy (absence to be confirmed by ß-human chorionic gonadotrophin test) or lactation period * Known drug abuse/alcohol abuse * Legal incapacity or limited legal capacity * Medical or psychological condition which in the opinion of the investigator would not permit the subject to complete the study or sign meaningful informed consent * Participation in another clinical study within the 30 days before randomization * Significant disease which, in the investigator's opinion, would exclude the subject from the study

Study Objectives This open-label, non-comparative, multi-center study will assess the safety profile and efficacy of Avastin (bevacizumab) when added to carboplatin and paclitaxel therapy in participants with epithelial ovarian cancer, fallopian tube carcinoma or primary peritoneal carcinoma. Participants will receive 15 milligrams/kilogram (mg/kg) Avastin intravenously (IV) on Day 1 of every cycle for up to 36 cycles of 3 weeks each, carboplatin (area under the plasma concentration-time curve \[AUC\] 5-6 mg/ml/min) on Day 1 every 3 weeks for a maximum of 8 cycles and paclitaxel 175 milligram per square meter (mg/m\^2) on Day 1 every 3 weeks or 80 mg/m\^2 every week for a maximum of 8 cycles. The anticipated time on study drug will be 108 weeks or until disease progression or unacceptable toxicity. Conditions: Ovarian Cancer Intervention / Treatment: DRUG: Paclitaxel, DRUG: Bevacizumab, DRUG: Carboplatin Location: Hungary, Canada, Portugal, Turkey, Lithuania, Egypt, Uruguay, Greece, Taiwan, Austria, France, Poland, Israel, India, Kuwait, Italy, Netherlands, Denmark, Ireland, South Africa, Russian Federation, Bulgaria, Estonia, Spain, Brazil, Serbia, Slovenia, Saudi Arabia, Latvia, Macedonia, The Former Yugoslav Republic of, Sweden, Mexico, Romania, Switzerland, Slovakia, Hong Kong, Argentina Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed epithelial ovarian carcinoma, fallopian tube carcinoma, primary peritoneal carcinoma or clear cell carcinoma or carcinosarcoma. Participants with recurrent ovarian cancer who have been previously treated with surgery alone for their early stage disease are eligible. * Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0, 1 or 2 * Life expectancy greater than or equal to (>=3) months Exclusion Criteria: * Participants with non-epithelial ovarian cancer, ovarian tumors with low malignant potential (i.e., borderline tumors), or synchronous primary endometrial carcinoma * Previous systemic therapy for ovarian cancer. Prior neo-adjuvant chemotherapy is allowed * Planned intraperitoneal cytotoxic chemotherapy * Radiotherapy within 28 days of Day 1, Cycle 1 * Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to first dose of Avastin * History or evidence of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade >=1 arterial thromboembolic event or Grade >=3 venous thromboembolic event within 6 months prior to enrollment

Study Objectives The purpose of this study is to see how vincristine, when placed in an oil droplet called a liposome (VSLI), is absorbed, distributed (moved around) and excreted from the the body (pharmacokinetics). This study will also assess the safety of VSLI and to see if VSLI will slow the growth or shrink tumors in patients with metastatic melanoma that has resulted in liver impairment, and who have relapsed after previous therapies. Conditions: Malignant Melanoma Intervention / Treatment: DRUG: Vincristine Sulfate Liposomes Injection 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, surgically nonresectable Stage III or IV metastatic cutaneous, mucosal, or choroidal melanoma, and not be eligible for a treatment protocol of a higher priority. * Patients must have secondary tumor involvement of the liver confirmed by CT scan and a bilirubin level of 1.6-3.0 mg/dL (National Cancer Institute, Common Terminology Criteria for Adverse Events Grade 2) (MD Anderson Cancer Center normal range is 0-1.0 mg/dL). * Patients must have bidimensionally measurable disease. * Patients with nonchoroidal melanoma must have received prior chemotherapy for metastatic disease with cytotoxic or biological drugs. Patients with choroidal melanoma may or may not have received prior chemotherapy for metastatic disease with cytotoxic or biological drugs. * Patients must have a Performance Status of 0, 1, 2, or 3 (Zubrod Scale). * Patients must have recovered from the adverse effects of prior chemotherapy (including cytotoxic agents and biological response modifiers), and/or irradiation therapy. * Patients must have an absolute neutrophil count >=1.0 x 10*9/L and a platelet count of >=100 x 10*9/L. * Patients must have adequate renal function demonstrated by a creatinine level of <=2.0 mg/dL. * Patients must have a life expectancy of >8 weeks. * Patients must provide a signed informed consent document indicating that they are aware of the investigational nature of this study in keeping with the policies of the hospital. Exclusion Criteria: * Patients treated with radiotherapy, chemotherapy, immunotherapy, vaccine treatment and/or alternative anticancer treatments (including investigational drugs) within 3 weeks prior to study enrollment. * Patients treated with hepatic chemo-embolization within 4 weeks prior to study enrollment. * Patients with severe hepatic impairment demonstrated by plasma ammonia levels >105 mMol/L or serum albumin <2.0 g/dL or serum bilirubin >3.0 mg/dL. * Patients with serious intercurrent illness. * Patients who have had major surgery within 4 weeks of enrollment. * Patients with advanced symptomatic central nervous system (CNS) involvement by melanoma and those on phenytoin or requiring steroids for brain metastases, spinal cord compression, or meningeal "carcinomatosis".Patients with asymptomatic and stable metastatic CNS disease can be enrolled. * Patients receiving treatment with phenytoin and/or corticosteroids within 1 week of enrollment. Patients must remain off of these medications for the duration of the treatment phase of the study. * Patients with a history of neurological disorders unrelated to chemotherapy (including familial neurological diseases and acquired demyelinating disorders). * Patients with Grade 3 or greater sensory, motor or autonomic neuropathy at screening from any cause. * Patients receiving treatment with drugs known to inhibit or induce hepatic drug metabolism by cytochrome P450-3A4 isoenzymes and/or P-glycoprotein within 1 week of study enrollment. Patients must remain off of these drugs until the collection of the Cycle 4 pretreatment PK sample. * Patients with past or current history of liver parenchymal or hepatobiliary disease unrelated to cancer (including but not limited to conditions such as liver cirrhosis, acute/chronic hepatitis, ascending cholangitis, etc). * Patients who are pregnant or lactating. Females of childbearing potential must have a negative urine or blood pregnancy test at screening. Both men and women must be practicing an adequate method of birth control for the duration of the study. Acceptable methods of birth control include use of an intrauterine device (IUD), oral contraceptive pills, implanted, transdermal, or injected contraceptives, barrier methods with spermicide, and abstinence. * Patients who are unable to return for follow up re-evaluation and assessment of response to VSLI.

Study Objectives This is a study in adults with advanced cancer (solid tumours) in whom previous treatment was not successful. The study tests 2 medicines called BI 1387446 and BI 754091. Both medicines may help the immune system fight cancer. In this study, BI 1387446 is given to humans for the first time. The purpose of this study is to find out the highest dose of BI 1387446 alone and in combination with BI 754091 the participants can tolerate. BI 1387446 is injected directly into the tumour. Participants get BI 1387446 injections every week at the beginning and then every 3 weeks. Some participants get BI 754091 in addition to BI 1387446. BI 754091 is given as an infusion into a vein every 3 weeks. As long as they benefit from treatment and can tolerate it, participants can stay in the study for up to 2 years and 8 months. During this time, they visit the study site regularly. At these visit, doctors record any unwanted effects. The doctors also regularly check participants' health. Conditions: Neoplasms Intervention / Treatment: DRUG: BI 1387446, DRUG: BI 754091 Location: United States, Spain, United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion criteria * Histologically or cytologically confirmed diagnosis of an advanced, unresectable and/or metastatic malignant solid tumor and indication for treatment * Patient must have exhausted established treatment options known to prolong survival for the malignant disease, or is not eligible for established treatment options. * Medically fit and willing to undergo all mandatory trial procedures. * At least one tumor lesion which is suitable for injection (Screening/initial administration), appropriate for the allocated treatment arm, and measurable. * At least 1 discrete lesion, in addition to the lesion proposed for injection, which is amenable to biopsy and is not located in the brain, mediastinum or pancreas. * Adequate organ function or bone marrow reserve * Further inclusion criteria apply Exclusion criteria: * Any investigational or antitumour treatment (including antibodies targeting Programmed Cell Death-1 (PD1) - or programmed Death-Ligand 1 (PDL1)) within 4 weeks or 5 half-life periods (whichever is shorter) prior to the initial administration of BI 1387446 or BI 754091. * Persistent toxicity from previous treatments (including Immune-related Adverse Events (irAEs)) that has not resolved to <= Grade 1, except for alopecia, xerostomia, and immunotherapy related endocrinopathies which may be included if clinically stable on hormone supplements or antidiabetic drugs as per Investigator judgement * History or evidence of active, non-treatment related autoimmune disease, except for endocrinopathies which may be included if clinically stable on hormone supplements or antidiabetic drugs. * History or evidence of pneumonitis related to prior immunotherapy * Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 2 weeks prior to the first dose of BI 1387446 or BI 754091. * The tumor at the projected injection site has a high risk for local complications, e.g. bleeding related to encasement/infiltration of major blood vessels or contact with liver capsule, compression of vital structures in case of swelling of injected lesion, in the opinion of the Investigator. * Active infection requiring systemic therapy at the start of treatment in the trial, including active viral hepatitis infection or active tuberculosis infection. * Cardiac insufficiency New York Heart Association (NYHA) III or IV * Left ventricular ejection fraction < 50% measured by echocardiography or Multigated Acquisition (MUGA) scan * Mean resting corrected QT interval (QTc) >470 msec * Further exclusion criteria apply

Study Objectives The standard of care for muscle-invasive bladder cancer (MIBC) is radical cystectomy, which is rarely curative. Platinum-based neoadjuvant chemotherapy is associated with an improvement in Overall Survival (OS), but only a few patients can benefit from this approach. Therefore, new neoadjuvant treatments are required for muscle- invasive bladder cancer. In this study it will be explored the activity of durvalumab plus olaparib in advanced Transitional Cell Carcinoma of the Bladder and therefore may have beneficial outcomes in the neoadjuvant setting. Adverse events associated with durvalumab and olaparib is one of the potential risks in this study. Participation in this trial, in which 6-8 weeks of preoperative treatment will be administered, is not expected to result in delays of surgery for participants. It is not foreseen that treatment with durvalumab and olaparib has a relevant impact on operability or increases the risks associated with surgery Conditions: Bladder Cancer Intervention / Treatment: DRUG: Durvalumab, DRUG: Olaparib Location: Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Written informed consent obtained from the subject prior to performing any protocol related procedures, including screening evaluations * Age >=18 years at time of study entry * Subjects with histological confirmation of T2-T4a urothelial bladder by transurethral resection * Patients aimed for cystectomy without neoadjuvant chemotherapy * Tumor tissue (archival or recent acquisition) from diagnostic Transurethral Resection (TUR) must be available (block or 5 - 15 unstained slides of formalin fixed paraffin embedded (FFPE) tissue) for correlative studies. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Exclusion Criteria. * Life expectancy of > 16 weeks * Body weight > 30kg * Normal organ and bone marrow function prior to administration of study treatment as defined below: * Haemoglobin > 10.0 g/dL with no blood transfusion in the past 28 days * Absolute neutrophil count (ANC) 1.5 x (> 1500 per mm3) * Platelet count >= 100 x 109/L (>100,000 per mm3) * Serum bilirubin <= 1.5 x institutional upper limit of normal (ULN). * Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) <= 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be <= 5x ULN * Serum creatinine Clearance > 51 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance. * Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal subjects within 28 days of study treatment and confirmed prior to treatment on day 1. * Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations. * Male patients and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination, throughout the period of taking study treatment and for 180 days after last dose of study drug(s) to prevent pregnancy in a partner. Female patients of child bearing potential and male patients with partners of child bearing potential, who are sexually active, must agree to the use of two highly effective forms of contraception throughout period of taking study treatment and for 1 month (female patients) / 3 months (male patients) after last dose of study drug. * At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by CT/MRI and is suitable for repeated assessment. * Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary cancer must be available for central testing. If there is not confirmation of the availability of an archived tumour sample prior to enrolment the patient is not eligible for the study Exclusion criteria: * Participation in another clinical study with an investigational product during the last 4 weeks * Concurrent enrolment in another clinical study, unless it is an observational (non- interventional) clinical study or during the follow-up period of an interventional study * Prior therapy with anti-PD-1, anti-PD-L1 including durvalumab, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (or any other antibody or drug specifically targeting T-cell co- stimulation or checkpoint pathways). * Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) <= 28 days prior to the first dose of study drug. * Resting electrocardiogram (ECG) with time between the start of the Q wave and the end of the T wave corrected for heart rate (QTc)> 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome. * Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. * Any unresolved toxicity National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade >=1 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria * Any concurrent chemotherapy, Investigational Product (IP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable. * Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug. * Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP and patients must have recovered from any effects of any major surgery. * Previous allogenic bone marrow transplant or double umbilical cord blood transplant (dUCBT). * Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable. * Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). * Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non- malignant systemic disease or active, uncontrolled infection. * Past medical history of Interstitial Lung Disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD. * Subjects with uncontrolled adrenal insufficiency * Known drug or alcohol abuse * History of another primary malignancy. * Patients with symptomatic uncontrolled brain metastases. * Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis (TB) testing in line with local practice), hepatitis B (known positive Hepatitis B Virus (HBV) surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core (HBc) antibody [anti-HBc] and absence of HBsAg) are eligible. Subjects positive for hepatitis C, HIV, or immunocompromised patients are eligible only if polymerase chain reaction is negative for Hepatitis C Virus (HCV) RNA. * Receipt of live attenuated vaccine within 30 days prior to the first dose of study treatment. * Female subjects who are pregnant or breastfeeding or male or female subjects of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of study treatment. * Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. * Prior randomisation or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment. * Prisoners or subjects who are involuntarily incarcerated. * Any previous treatment with poly ADP ribose polymerase (PARP) inhibitor, including olaparib. * Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks. * Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents. * Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MyeloDysplatic Syndrome (MDS) / acute myeloid leukemia (AML). * Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication. * Judgment by the investigator that the patient is unsuitable to participate in the study * Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) * Previous enrolment in the present study.

Study Objectives This screening and multi-sub-study randomized phase II/III trial will establish a method for genomic screening of similar large cancer populations followed by assigning and accruing simultaneously to a multi-sub-study hybrid ?Master Protocol? (S1400). The type of cancer trait (biomarker) will determine to which sub-study, within this protocol, a participant will be assigned to compare new targeted cancer therapy, designed to block the growth and spread of cancer, or combinations to standard of care therapy with the ultimate goal of being able to approve new targeted therapies in this setting. In addition, the protocol includes a ?non-match? sub-study which will include all screened patients not eligible for any of the biomarker-driven sub-studies. This sub-study will compare a non-match therapy to standard of care also with the goal of approval. Conditions: Recurrent Squamous Cell Lung Carcinoma, Stage IV Squamous Cell Lung Carcinoma AJCC v7 Intervention / Treatment: DRUG: Docetaxel, BIOLOGICAL: Durvalumab, DRUG: Erlotinib Hydrochloride, DRUG: FGFR Inhibitor AZD4547, BIOLOGICAL: Ipilimumab, OTHER: Laboratory Biomarker Analysis, BIOLOGICAL: Nivolumab, DRUG: Palbociclib, OTHER: Pharmacological Study, BIOLOGICAL: Rilotumumab, DRUG: Talazoparib, DRUG: Taselisib, BIOLOGICAL: Tremelimumab Location: United States, Canada Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * SCREENING/PRE-SCREENING REGISTRATION: * Patients must have pathologically proven squamous cell carcinoma (SCCA) cancer of the lung confirmed by tumor biopsy and/or fine-needle aspiration; disease must be stage IV SCCA, or recurrent; the primary diagnosis of SCCA should be established using the current World Health Organization (WHO)/International Association for the Study of Lung Cancer (IASLC)-classification of Thoracic Malignancies; the diagnosis is based on hematoxylin and eosin (H&E) stained slides with or without specific defined immunohistochemistry (IHC) characteristic (p40/p63 positive, transcription termination factor [TTF1] negative) if required for diagnosis; mixed histologies are not allowed * Patients must either be eligible to be screened at progression on prior treatment or to be pre-screened prior to progression on current treatment; patients will either consent to the screening consent or the pre-screening consent, not both; these criteria are: * Screening at progression on prior treatment: to be eligible for screening at progression, patients must have received at least one line of systemic therapy for any stage of disease (stages I-IV) and must have progressed during or following their most recent line of therapy; for patients whose prior systemic therapy was for stage I-III disease only (i.e. patient has not received any treatment for stage IV or recurrent disease), the prior systemic therapy must have been a platinum-based chemotherapy regimen and disease progression on the platinum-based chemotherapy must have occurred within one year from the last date that patient received that therapy; for patients whose prior therapy was for stage IV or recurrent disease, the patient must have received at least one line of a platinum-based chemotherapy regimen or checkpoint inhibitor therapy (e.g. nivolumab or pembrolizumab) * Pre-screening prior to progression on current treatment: to be eligible for pre-screening, current treatment must be for stage IV or recurrent disease and patient must have received at least one dose of the current regimen; patients must have previously received or currently be receiving a platinum-based chemotherapy regimen or checkpoint inhibitor therapy (e.g. nivolumab or pembrolizumab); patients on first-line platinum-based treatment are eligible upon receiving cycle 1, day 1 infusion; Note: patients will not receive their sub-study assignment until they progress and the S1400 Notice of Progression is submitted * Patients must have adequate tumor tissue available, defined as >= 20% tumor cells and >= 0.2 mm^3 tumor volume * The local interpreting pathologist must review the specimen * The pathologist must sign the S1400 Local Pathology Review Form confirming tissue adequacy prior to screening/pre-screening registration * Patients must agree to have this tissue submitted to Foundation Medicine for common broad platform Clinical Laboratory Improvement Act (CLIA) biomarker profiling; if archival tumor material is exhausted, then a new fresh tumor biopsy that is formalin-fixed and paraffin-embedded (FFPE) must be obtained; a tumor block or FFPE slides 4-5 microns thick must be submitted; bone biopsies are not allowed; if FFPE slides are to be submitted, at least 12 unstained slides plus an H&E stained slide, or 13 unstained slides must be submitted; however it is strongly recommended that 20 FFPE slides be submitted; Note: previous next-generation deoxyribonucleic acid (DNA) sequencing (NGS) will be repeated if done outside this study for sub-study assignment; patients must agree to have any tissue that remains after NGS testing retained for the use of the translational medicine (TM) studies (if such TM studies are defined) within any sub-study the patient is enrolled in * Patients must not have a known epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) fusion; EGFR/ALK testing is not required prior to registration and is included in the Foundation Medicine Incorporated (FMI) testing for screening/prescreening * Patients must have Zubrod performance status 0-1 documented within 28 days prior to screening/pre-screening registration * Patients must also be offered participation in banking for future use of specimens * Patients must be willing to provide prior smoking history as required on the S1400 Onstudy Form * As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system * Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines * SUB-STUDY REGISTRATION: * Patients whose biomarker profiling results indicate the presence of an EGFR mutation or echinoderm microtubule-associated protein-like 4 (EML4)/ALK fusion are not eligible * Patients must have progressed (in the opinion of the treating investigator) following the most recent line of therapy * Patients must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 21 days prior to sub-study registration; patients must have recovered (=< grade 1) from any side effects of prior therapy; patients must not have received any radiation therapy within 14 days prior to sub-study registration * Patients must have measurable disease documented by computed tomography (CT) or magnetic resonance imaging (MRI); the CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality; measurable disease must be assessed within 28 days prior to sub-study registration; pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease; non-measurable disease must be assessed within 42 days prior to sub-study registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form; patients whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to registration * Patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to sub-study registration; patient must not have leptomeningeal disease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment and prior to registration, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to sub-study registration * Patient must have fully recovered from the effects of prior surgery at least 14 days prior to sub-study registration * Patients must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment; concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable * Absolute neutrophil count (ANC) >= 1,500/mcl obtained within 28 days prior to sub-study registration * Platelet count >= 100,000 mcl obtained within 28 days prior to sub-study registration * Hemoglobin >= 9 g/dL obtained within 28 days prior to sub-study registration * Serum bilirubin =< institutional upper limit of normal (IULN) within 28 days prior to sub-study registration; for patients with liver metastases, bilirubin must be =< 5 x IULN * Either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 2 x IULN within 28 days prior to sub-study registration (if both ALT and AST are done, both must be =< 2 IULN); for patients with liver metastases, either ALT or AST must be =< 5 x IULN (if both ALT and AST are done, both must be =< 5 x IULN) * Serum creatinine =< the IULN OR measured or calculated creatinine clearance >= 50 mL/min using the following Cockcroft-Gault Formula within 28 days prior to sub-study registration * Patients must have Zubrod performance status 0-1 documented within 28 days prior to sub-study registration * Patients must not have any grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, and myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia * Patients must not have documented evidence of acute hepatitis or have an active or uncontrolled infection * Patients with a known history of human immunodeficiency virus (HIV) seropositivity: * Must have undetectable viral load using standard HIV assays in clinical practice * Must have cluster of differentiation (CD)4 count >= 400/mcL * Must not require prophylaxis for any opportunistic infections (i.e., fungal, Mycobacterium avium complex [mAC], or pneumocystis jiroveci pneumonia [PCP] prophylaxis) * Must not be newly diagnosed within 12 months prior to sub-study registration * Prestudy history and physical exam must be obtained within 28 days prior to sub-study 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 five years * Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures * As part of the OPEN registration process the treating institution?s identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the system * Patients with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator) * Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

Study Objectives This study is being conducted to demonstrate the superiority in progression-free survival (PFS) of dinaciclib compared to ofatumumab in chronic lymphocytic leukemia (CLL) participants with del 17p or in the overall population who are refractory to either fludarabine treatment or chemoimmunotherapy. Conditions: Chronic Lymphocytic Leukemia (CLL) Intervention / Treatment: DRUG: Dinaciclib, DRUG: Ofatumumab Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Aged >= 18 years * Confirmed diagnosis of Chronic Lymphocytic Leukemia (CLL) * Fludarabine or chemoimmunotherapy refractory disease defined as: failing to respond to or relapsed within 6 months of completing fludarabine or another purine analog alone or in combination regimens, or failing to respond to chemoimmunotherapy or relapsed within 24 months of completing therapy with a combination of chemotherapy plus an anti-CD20 monoclonal antibody * Eastern Cooperative Oncology Group (ECOG) Performance status 0, 1, or 2 * Adequate organ function and laboratory parameters * Women of child-bearing potential who are not currently sexually active must agree to use a medically accepted method of contraception should they become sexually active while participating in the study Exclusion Criteria: * Symptomatic brain metastases or primary central nervous system malignancy * Treatment with a CYP3A4 inhibitor or inducer within 1 week prior to randomization, or any chemotherapy or biologic therapy within 4 weeks prior to randomization * Known human immunodeficiency virus (HIV) infection or a known HIV-related malignancy * Participants with with clinically active hepatitis B or C defined as disease that requires therapy * Positive test for glucose-6 phosphate dehydrogenase (G6PD) deficiency * Prior allogeneic bone marrow transplant * Presence of Richter's transformation * Indeterminate deletion 17p status * Previous treatment with ofatumumab, dinaciclib, or other CDK inhibitors * Active autoimmune anemia or thrombocytopenia unless stable, which is defined as being responsive to corticosteroids or other standard therapy

Study Objectives The purpose of this study is to determine the efficacy of SyB L-0501 in combination with rituximab in patients with recurrent/relapsed diffuse large B-cell lymphoma. Conditions: Assess the Efficacy and Safety of SyB L-0501 in Combination With Rituximab in Patients With Recurrent or Relapsed DLBCL Intervention / Treatment: DRUG: Rituximab Location: Japan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion criteria Patients who satisfy all of the conditions listed below. * Patients with histopathologically confirmed diffuse large B-cell lymphoma (DLBCL) except for transformed lymphoma on the basis of World Health Organization (WHO) histological classification (4th ed., 2008). * Patients with documented Cluster of differentiation 20 (CD20)-positive for lymphoma cells. * Patient with recurrent or relapsed DLBCL after R-CHOP-like theraphy as the firstline therapy. * Patients with measurable lesions >1.5 cm in major axes. * Patients who are expected to survive for at least 3 months. * Patients aged 20 or above at the time informed consent is obtained. * Patient with Performance Status (P.S.) 0-1. * Patients with adequately maintained organ function. Exclusion Criteria The study subject should be excluded if any one of the following condition exists. * Patients who have been without treatment for less than 3 weeks after prior treatment. * Patients who can be candidates for autologous peripheral blood stem cell transplantation at the discretion of the investigator. * Patients who received adequate prior treatments and did not respond to any of them. * Patient who received prior chemotherapy 3 regimens or more. * Patients with central nervous system (CNS) involvement or patients with clinical symptoms suggestive of CNS involvement. * Patient with serious active infection. * Patient with serious complication. * Patient with complication or medical history of serious cardiac disease. * Patient with serious gastrointestinal symptoms. * Patient with malignant pleural effusion, pericardial effusion, or ascites retention. * Patients positive for hepatitis B surface (HBs) antigen, hepatitis C virus (HCV) antibody, or HIV antibody. * Patient with serious bleeding tendency. * Patient with a fever of 38.0°C or higher. * Patients with, or confirmed in the past to have had, interstitial pneumonia, pulmonary fibrosis, or pulmonary emphysema. * Patients with active multiple primary cancer or patients with a history of other malignant cancer within the past 5 years, except for basal cell cancer of the skin, squamous cell cancer, or cervical cancer in situ. * Patients with, or confirmed in the past to have had, autoimmune hemolytic anemia. * Patient who received bendamustin hydrochloride in the past. * Patients who received cytokine preparation such as erythropoietin or granulocyte colony-stimulating factor (G-CSF) or blood transfusions within 2 weeks before the examination at registration for this study.

Study Objectives Recent advances in allogeneic hematopoietic cell transplantation (allo-SCT) have led to reduce intensity preparative regimens that are non-myeloablative and reduce the toxicities associated with the transplant. Consequently non-relapse mortality has been reduced, including in elderly patients with comorbidities. However, despite this benefit in terms of toxicity, excessive reduction of the intensity preparative regimens may favor relapse of the initial illness. Thus, acute and chronic graft-versus-host disease and opportunistic fungal and viral infections are always serious complications. The aim of our study is to check if a new modality of reduced intensity preparative regimen combining total lymphoid irradiation (TLI) and thymoglobulin (ATG), would limit the toxicity of treatment and reduce the incidence of acute GVHD after allogeneic transplantation while preserving the antitumor benefit. Conditions: Haemato-lymphoid Malignancies or Syndromes in Whom Allogeneic Stem Cell Transplantation is Warranted Intervention / Treatment: DRUG: total lymphoid irradiation and anti-thymocyte globulin Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Any patient with one of the following hemato-lymphoid malignancies or syndromes in whom allogeneic stem cell transplantation is warranted. Specific disease categories include: non-follicular indolent advanced stage Non-Hodgkin Lymphomas, Mantle Cell Lymphoma, Marginal zone lymphoma, MALT, T cell lymphoma, Chronic Lymphocytic or prolymphocytic Leukemia, Hodgkin Disease, and Waldenström macroglobulinemia. T-cell NOS, angioimmunoblastic lymphoma, HTLV1, T-gamma/delta, anaplastic lymphoma and Sezeay syndromes can be included after careful assessment by the PI and the protocol steering committee. * Patients must be at least in partial remission (according to standard criteria) after salvage therapy and before (~one month) the start of the conditioning regimen. * Patient age >50 and less than 66 years, or for patients <50 years of age but because of pre-existing medical conditions or prior therapy are considered to be at high risk for regimen-related toxicity associated with conventional myeloablative transplants. * A fully HLA-identical sibling or matched unrelated donor is available (10/10 HLA match). Patients with one antigen mismatched donors can be considered but only after discussion with the transplant team and the Principal Investigator. * Patient must be competent to give consent. Exclusion Criteria: * Patients with progressive hematolymphoid malignancies despite conventional therapies, and not in partial remission during the month preceding transplantation. * Patients with DLBCL or cutaneous T cell lymphoma * Uncontrolled CNS involvement with disease * Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment * Females who are pregnant * Organ dysfunction defined as follows: * Cardiac function: ejection fraction <30% or uncontrolled cardiac failure * Pulmonary: DLCO <40% predicted * Renal: Serum creatinine >1.0 mg/dL; if serum creatinine >1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m² * Liver function abnormalities: elevation of bilirubin to > 3 mg/dl and/or transaminases >4x the upper limit of normal * Karnofsky performance score < 70% * Patients with poorly controlled hypertension on multiple antihypertensives * Documented fungal disease that is progressive despite treatment * Viral infections: HIV positive patients. Hepatitis B and C positive patients will be evaluated on a case by case basis * Psychiatric disorders or psychosocial problems which in the opinion of the primary physician or Principal Investigator would place the patient at unacceptable risk from this regimen. * Patients with prior malignancies diagnosed > 5 years ago without evidence of disease are eligible. Patients with a prior malignancy treated < 5 years ago but have a life expectancy of > 5 years for that malignancy are eligible.

Study Objectives The purpose of this study is to examine the long-term safety and tolerability of human corticotropin-releasing factor (hCRF), XERECEPT®, in patients requiring dexamethasone (Decadron) to treat peritumoral brain edema. This open-label, extended-use study is open to all patients who participate in either of the blinded studies, NTI 0302, NTI 0303, or other designated studies, including patients who may have discontinued blinded study medication early but completed the protocol-stipulated follow-up periods. Conditions: Brain Edema, Brain Tumor Intervention / Treatment: DRUG: hCRF [XERECEPT (corticorelin acetate injection)] Location: United States, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Participation in and completion of stipulated final follow-up periods for study NTI 0302, NTI 0303, or other designated studies. * Have a Karnofsky Performance of > 50 at Baseline * Capable of self-administration of subcutaneous injections twice daily or availability of assistance from caregiver. * Ability to provide written informed consent or, if unable to provide, have a legal guardian or representative provide written informed consent. * For women of childbearing potential: a negative serum pregnancy test at Baseline Exclusion Criteria: * Concurrent enrollment in any investigational drug or device study, other than NTI 0302, NTI 0303, or other designated studies. * Systemic steroid use for any indication other than peritumoral brain edema. * Use or intended use of dexamethasone as an anti-emetic during study. * Clinical signs and symptoms of cerebral herniation. * Serious concomitant cardiovascular, pulmonary, renal, gastrointestinal or endocrine metabolic disease which could put the patient at unusual risk during study participation. * Confounding previous or concurrent neurological disorders that would interfere with adequate clinical evaluation. * Clinically significant head injury or chronic seizure disorder, if the condition results in functional impairment or is likely to interfere with evaluations.(Maintenance anticonvulsant therapy is allowed) * Central nervous system (CNS) infection. * Pregnancy, breastfeeding and/or refusal to practice birth control while in study, for women of childbearing potential.

Study Objectives This randomized phase II trial compares how well two different doses of carfilzomib work when given with dexamethasone in treating patients with multiple myeloma that has come back after a period of improvement or has not responded to treatment. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving carfilzomib together with dexamethasone may kill more cancer cells. It is not yet known whether a higher or lower dose of carfilzomib works better when given with dexamethasone. Conditions: Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma Intervention / Treatment: DRUG: Carfilzomib, DRUG: Dexamethasone, OTHER: Laboratory Biomarker Analysis Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * REGISTRATION STEP 1: INITIAL RANDOMIZATION * Patients must have a confirmed diagnosis of symptomatic multiple myeloma and must be currently relapsed or refractory; all tests for establishing disease status must be completed within 28 days prior to registration and documented on the Baseline Tumor Assessment Form for Multiple Myeloma * Patients must have measurable disease within 28 days prior to registration * Patients must have received at least one prior regimen of chemotherapy for symptomatic multiple myeloma; patients may not have more than six (6) previous regimens of therapy for the disease; prior chemotherapy must have been completed at least 21 days prior to registration; for study purposes, a regimen is defined as follows: * An anti-myeloma therapy used at the time of initial diagnosis or documented disease progression which is given with the intent to decrease disease burden * Any maintenance therapy used after an Induction should be considered part of that Induction regimen * Use of any agent or combination of agents more than once during the patient's disease history for separate documented disease progressions will be counted as separate regimens (e.g., if a patient receives lenalidomide/bortezomib at initial diagnosis and achieves response, but then progresses and receives lenalidomide/bortezomib after progression, these count as 2 separate regimens) * In cases of allogeneic or autologous stem cell transplant, the entire induction + stem cell mobilization + conditioning + planned maintenance should be considered one regimen * Patients may not have received any prior carfilzomib treatment * Patients must not be receiving any other concurrent therapy considered to be investigational; patients must not be planning to receive any radiotherapy (except localized radiation for palliative care); patients must not be planning to receive any concurrent chemotherapy, immunotherapy, radiotherapy or other treatment with curative intent * Patients must have complete history and physical examination within 28 days prior to registration * Patients must have baseline PET scan within 28 days prior to registration; note that images are submitted centrally for review * Patients with non-secretory MM or known primary amyloidosis are not eligible * Patients must have Zubrod performance status 0-2 * Patients must not have clinically significant illness including uncontrolled, active infection requiring intravenous antibiotics, New York Heart Association (NYHA) class III or class IV heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or >= grade 3 cardiac arrhythmias * Patients must have undergone an electrocardiogram (EKG) within 28 days prior to registration * Patients must have either echocardiogram (ECHO) with ejection fraction >= 45% within 28 days prior to registration * Patients must not have > grade 2 neuropathy and/or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) * Total bilirubin =< 1.5 x upper limit of normal (ULN) * Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 3 x ULN * Absolute neutrophil count (ANC) >= 1,000 cell/mm^3 without growth factor support within 14 days prior to registration * Platelets >= 50,000 cells/mm^3 for patients who have bone marrow plasmacytosis < 50% or >= 30,000 cells/mm^3 for patients who have bone marrow plasmacytosis of >= 50% within 14 days prior to registration * Calculated or measured creatinine clearance >= 30 ml/min within 14 days prior to registration * Patients who are known to be human immunodeficiency virus positive (HIV+) are eligible providing they meet all of the following additional criteria within 28 days prior to registration: * Cluster of differentiation (CD)4 cells >= 500/mm^3 * Viral load of < 50 copies HIV messenger ribonucleic acid (mRNA)/mm^3 if on combination antiretroviral therapy (cART) or < 25,000 copies HIV mRNA if not on cART * No zidovudine or stavudine as part of cART * Patients who are HIV+ and do not meet all of these criteria are not eligible for this study * Patients with known hepatitis B or hepatitis C infection must have viral load < 800,000 IU/L within 28 days prior to registration * Patients must have baseline skeletal survey to document lytic lesions, osteopenia or compression fracture within 28 days prior to registration * Patients may have received palliative external beam radiation therapy (XRT) for local disease control with no curative intent. XRT must be completed at least 7 days prior to registration * Patients must be offered participation in specimen submission for translational medicine studies and banking; with patient consent, specimens must be submitted * Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures * 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 three years * Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines * As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system * REGISTRATION STEP 2: CROSSOVER * Patient must have been eligible for and initially randomized to Arm 1 (low dose carfilzomib), begun cycle 2 of treatment, and progressed prior to completing 12 cycles of protocol therapy * At least 14 days and no more than 28 days must have elapsed between the last day of treatment on Arm 1 and registration to Arm 3 * Patients must have recovered from all non-hematologic toxicities to =< grade 2 and from all hematologic toxicities to =< grade 3 prior to registration * Patients must have begun cycle 2 (carfilzomib - 27 mg/m^2) and must not have received any dose reduction for toxicity in the last cycle of treatment, immediately preceding progression * Patients must have serum protein electrophoresis (SPEP) and kappa and lambda light chain testing performed within 14 days prior to registration in order to establish baseline measurements * Patients must not have ejection fraction decrease > 10% from baseline (as determined by ECHO) or other ejection fraction decrease accompanied by other clinical signs/symptoms of New York Heart Association (NYHA) class III or IV heart failure, measured within 28 days prior to registration; if any question exists regarding individual patient eligibility in this situation, contact the study chair for determination

Study Objectives This phase I trial studies the side effects and best dose of giving pemetrexed disodium and sorafenib tosylate together in treating patients with advanced solid tumors. Pemetrexed disodium and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib tosylate may also stop the growth of solid tumors by blocking blood flow to the tumor. Giving pemetrexed disodium together with sorafenib tosylate may kill more tumor cells. Conditions: Unspecified Adult Solid Tumor Intervention / Treatment: DRUG: sorafenib tosylate, DRUG: pemetrexed disodium, OTHER: laboratory biomarker analysis, PROCEDURE: biopsy 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: * Advanced solid tumor malignancy for which there is no potentially curative treatment; there is no limit to the number of prior lines of therapy * Performance status Eastern Cooperative Oncology Group (ECOG) equal or less than 1 * Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 3 x upper institutional limit (ULN) * Total bilirubin =< 1.5 ULN * Creatinine clearance (CrCl) >= 45 mL/min as measured by the standard Cockcroft-Gault equation * International normalized ratio (INR) =< 1.5 (if not due to anticoagulants) * White blood cell count (WBC) >= 3,000 cells/mm3 * Absolute neutrophil count (ANC) >= 1,500 cells/mm3 * Platelets >= 100,000 cells/mm3 * Hemoglobin (Hgb) >= 8.5 g/dL * Prior toxicities are allowed as long as they are stable and would not interfere with study drug toxicity assessment * Measurable or evaluable disease by Response Evaluation Criteria In Solid Tumors (RECIST) (v 1.1) * Ability to understand and the willingness to sign a written informed consent document; a signed informed consent must be obtained prior to any study specific procedures * Women of childbearing potential must have a negative pregnancy test performed within 7 days prior to the start of treatment; women of childbearing potential and men must agree to use a medically accepted form of birth control for the duration of study participation; men must agree to use a medically accepted form of birth control for 2 months following completion of study treatment Exclusion Criteria: * Any investigational agent within 4 weeks of first dose of study treatment * Unwillingness or inability to take folic acid, vitamin B12, or dexamethasone * Known or presumed intolerance of pemetrexed or sorafenib; unable to swallow medication; suspected malabsorption * Active illicit substance or alcohol abuse * Contraindication to antiangiogenic agents, including: * Pulmonary hemorrhage/bleeding event >= Grade 2 within 4 weeks or less prior to the first dose of study drug * Any other hemorrhage/bleeding event >= Grade 3 within 4 weeks or less prior to the first dose of study drug * Serious non-healing wound, ulcer, or bone fracture * Thrombolic or embolic events such as a myocardial infarction, cerebrovascular accident including transient ischemic attacks within the past 6 months * Major cardiac dysfunction, such as uncontrolled angina, congestive heart failure with New York Heart Association (NYHA) class III or higher, ventricular arrhythmias requiring anti-arrhythmic therapy * Systolic blood pressure > 160 mmHg or diastolic pressure > 100 mmHg despite optimal medical management * Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents for a 5 day period * Serious uncontrolled infection > Common Terminology Criteria for Adverse Events (CTCAE) (v 4) grade 2 * Peripheral motor or sensory neuropathy>CTCAE (v4) grade 2 * Uncontrolled metastatic brain disease * Serum B12 or folate levels below the institution's lower limit of normal. Patients may begin B12/folic acid supplementation and can be reconsidered for study once levels meet the eligibility requirements * Administration of non-steroidal anti-inflammatory drugs (NSAIDs) within 5 days prior to pemetrexed dosing (note: if a candidate routinely takes NSAIDs prior to enrollment, consider transition to alternate non-NSAID for duration of study treatment, if possible). * Other condition(s) that in the opinion of the investigator might compromise the objectives of the study

Study Objectives The purpose of this research study is to evaluate the effectiveness and safety of SOM230C in treating recurrent meningiomas. SOM230C is a newly discovered drug that may stop meningioma cells from growing abnormally. This drug has been used in treatment of other tumors, and information from those other research studies suggests that SOM230C may help to stop the growth of meningiomas. Conditions: Meningioma Intervention / Treatment: DRUG: SOM230C 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: * 18 years of age or older * Radiographically measurable disease on contrast-enhanced MRI or CT images * Karnofsky Performance status of 60 or greater * Life expectancy of at least 3 months * Histologically confirmed diagnosis of recurrent or progressive intracranial meningioma(s). This includes benign, atypical, or malignant meningioma; patients with neurofibromatosis type 1 or 2 may participate. Participants without histological confirmation but a classic radiographic picture of meningioma may also enroll. Patients with neurofibromatosis type 2 and a classic radiographic picture of meningioma may also enroll without histological confirmation * At least ten unstained standard (4-5 micron) paraffin slides for immunohistochemistry. Participants who have not had a surgical procedure are exempt from this requirement * Unequivocal evidence for tumor progression by MRI (or CT scan if MRI is contraindicated) * MRI or CT must be performed within 14 days of registration * Patients with malignant meningiomas who require corticosteroids must be on a stable dose for at least 5 days prior to baseline imaging. * For patients who have been treated with external beam radiation, interstitial brachytherapy, or radiosurgery, an interval of 4 or more weeks must have elapses from the completion of radiation therapy to study drug administration, and there must be evidence of tumor progression. * There is no limit on the number of prior therapies Exclusion Criteria: * Any cytotoxic chemotherapy, radiation, immunotherapy, or experimental therapy within 4 weeks prior to study drug administration * Prior therapy with somatostatin, andy somatostatin analogue, or any other hormonal treatment prescribed for the purpose of treating meningioma * Major surgery within 4 weeks prior to study drug administration * Malabsorption syndrome, short bowel or chologenic diarrhea not controlled by specific therapeutic means * Poorly controlled diabetes mellitus * Symptomatic cholelithiasis * Congestive heart failure, unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the six months preceding enrollment * QTc > 450 msec * Risk factors for Torsades de Pointes such as hypokalemia (< 3.5 mmol/L) not corrected by treatment, hypomagnesemia (< 0.7 mmol/L or < 1.6 mg/dL) not corrected by treatment, 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), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure * Concomitant medication(s) known to increase the QT interval within 4 weeks prior to study drug administration * Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis with serum bilirubin > 2x ULN, serum albumin < 0.67 LLN, or ALT or AST more than 2 x ULN * Any other primary malignancy within the past 3 years (with the exception of basal cell carcinoma or carcinoma in situ of the cervix) * Active or suspected acute or chronic, uncontrolled infection or any history of immunocompromise, including any positive HIV test result * Abnormal coagulation studies (PT or PTT elevated by 30% above normal limits) * Use of anticoagulant medications (not including anti-platelet medications) * Lab values as specified in the protocol * Any current or prior medical condition that may interfere with the conduct of the study or the evaluation of its results in the opinion of the investigator * Pregnancy or lactation, or failure to practice a medically acceptable method of birth control * History of alcohol or drug abuse in the 6 month period before study enrollment * Participation in any clinical investigation with an investigational drug within 1 month prior to study drug administration * Known hypersensitivity to somatostatin analogues or any component of the pasireotide or octreotide LAR os s.c. formulations

Study Objectives The primary purpose of this study is to determine the objective response rate (complete and partial response) for participants who receive tasisulam after one prior systemic treatment for unresectable or metastatic melanoma. Conditions: Metastatic Melanoma Intervention / Treatment: DRUG: tasisulam Location: United States, Australia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Diagnosis of malignant melanoma that is unresectable or metastatic (Stage III or IV) * Have received 1 previous systemic treatment regimen for unresectable or metastatic melanoma. An immunotherapy or antibody-based regimen (including vaccination-based treatments) is not counted as a prior treatment regimen for determining study eligibility, unless it was combined with a chemotherapeutic or targeted anti-cancer drug. * Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, immunotherapy, or other investigational therapy for at least 30 days Exclusion Criteria: * Serious pre-existing medical conditions * Have received two or more previous treatment regimens for unresectable or metastatic melanoma * Have a second primary cancer (unless disease-free to more than 2 years) * Active treatment with Warfarin (Coumadin) * Primary ocular or mucosal melanoma

Study Objectives Dose dense chemotherapy, which is the term for Adriamycin and Cyclophosphamide (AC) followed by Taxol chemotherapy given every two weeks, is the standard chemotherapy for the treatment of ER+ or PR+ breast cancer. In this trial, the standard chemotherapy is being combined with bevacizumab. Bevacizumab is an antibody which works differently from the way other chemotherapy drugs work. Bevacizumab slows or stops cell growth in cancerous tumors by decreasing the blood supply to the tumors by binding to a substance found on cancer cells called VEGF (vascular endothelial growth factor). Bevacizumab is approved by the FDA for the treatment of colorectal cancer and lung cancer. However, it is not approved for the treatment of breast cancer. Another goal of this research is to determine whether we can develop a way to identify tumors that will respond well to this study treatment. Conditions: Breast Cancer Intervention / Treatment: DRUG: Doxorubicin, DRUG: Cyclophosphamide, DRUG: Paclitaxel, DRUG: Bevacizumab Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Documented primary invasive breast cancer by histologic assessment * Tumors must express estrogen (ER) and/or progesterone receptors (PR) by standard immunohistochemical methods. Tumors must be negative for HER2. There must be sufficient sample for further protocol-specified immunohistochemical analysis * Patients must have high risk ER+ or PR+ breast cancer as defined by criteria listed in protocol * 18 year of age or older * Performance status of 0 or 1 by ECOG criteria * Use of an effective means of contraception in subjects of childbearing potential * Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to starting therapy. * Patients taking exogenous sex-steroid hormone treatments for any reason at the time of diagnosis must discontinue all hormonal treatments at least 2 weeks prior to enrollment * Patients must have preoperative treatment within 60 days of initial diagnosis of breast cancer * No other malignancy that requires on-going treatment * Normal organ function as outlined in the protocol Exclusion Criteria: * Prior cytotoxic chemotherapy or radiation for the current breast cancer * Patients with inflammatory breast cancer * HER2 positive disease defined as HER2-amplified by FISH or IHC 3+. HER2 2+ must be negative by FISH * Known metastatic (Stage IV) disease * Other investigational agents within 4 weeks prior to the start of study treatment * Life expectancy of less than 6 months * Peripheral neuropathy greater than or equal to grade 2 * Inadequately controlled hypertension * Any prior history of hypertensive crisis or hypertensive encephalopathy * NYHA grade II or greater congestive heart failure * History of prior myocardial infarction * History of unstable angina within 12 months prior to study enrollment * Any history of stroke or transient ischemic attack at any time * Known CNS disease * Significant vascular disease * Symptomatic peripheral vascular disease * Evidence of significant bleeding within 6 months of study; any serious non-healing wound, skin ulcers, or bone fracture; any abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within the past 6 months; any major surgical procedure within 28 days prior to randomization or anticipation of need for major surgery during course of study. * Known HIV positive * Unwilling to undergo pretreatment biopsy and consent to acquisition of archival tissue * Pregnant of lactating * Known hypersensitivity to any component of bevacizumab

Study Objectives The study has the purpose to compare R-CHOP versus R-mini-CEOP in elderly patients (\>65 years) with Diffuse Large B Cell Lymphoma (DLBCL). Conditions: Elderly Patients (>65 Years), Diffuse Large B Cell Lymphoma (DLBCL) Intervention / Treatment: DRUG: Cyclophosphamide, DRUG: Cyclophosphamide, DRUG: Doxorubicin, DRUG: Vincristine, DRUG: Prednisone, DRUG: Prednisone, DRUG: Epirubicin, DRUG: Vinblastine, DRUG: Rituximab, DRUG: G-CSF Location: Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patients with untreated DLBCL aged 66 to 80 years without major accompanying diseases and considered as "non frail". * Patients were classified as "non frail" (fit) if they had * ADL (Activity of Daily Living) score of 6 * less than three grade 3 Cumulative Illness Rating Score for Geriatrics (CIRS-G) co-morbidities and no grade 4 co-morbidities * absence of geriatric syndrome * Patients HIV negativity; * Concurrent malignancy; * Written Informed Consent. Exclusion Criteria: * All other patients were classified as "unfit", and were excluded from randomization

Study Objectives This clinical trial is a prospective, multicenter, self-controlled clinical study. In order to meet the requirements of this plan, 130 breast cancer patients need the sentinel lymph node biopsy with novel near-infarred fluorescence imaging system produced by Beijing digital precision medical technology co., LTD. The fluorescence molecular imaging of indocyanine green (ICG) on imaging detection and the control group, routine medical using methylene blue test .The safety and efficacy of fluorescence and staining in sentinel lymph node biopsy of breast cancer were compared. Conditions: Sentinel Lymph Node, Breast Cancer Intervention / Treatment: DRUG: Methylene Blue, DRUG: Indocyanine Green Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * the age of 18-75 years, female patients; * the diagnosis of breast cancer by biopsy; * participants voluntarily participated in the clinical trial and signed informed consent. Exclusion Criteria: * had received SLNB or axillary surgery; * breast area radiotherapy or neoadjuvant chemotherapy has been accepted. * clinical hints of axillary lymph node metastasis; * discovery of distant metastasis; * inflammatory breast cancer; * women in pregnancy; * people with iodine allergy; * the serum creatinine was > 1.5 times as high as the upper limit of the normal value. * to participate in clinical trials of other devices or drugs within one month; * the researchers consider it inappropriate to participate in this clinical trial.

Study Objectives This trial is designed to assess the tolerability and efficacy of simvastatin plus FOLFIRI (irinotecan, 5-FU, leucovorin) in metastatic colorectal cancer patients. Conditions: Colorectal Cancer, Metastasis Intervention / Treatment: DRUG: simvastatin Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed metastatic colorectal cancer * Age >= 18 * ECOG performance status 0 - 2 * At least one measurable lesion * Minimum life expectancy of 12 weeks * Adequate bone marrow reservoir (ANC >= 1500/㎕, platelet >= 100,000/㎕) * Adequate renal function (serum creatinine <= 1.5 mg/dl or creatinine clearance >= 50 min/ml) * Adequate liver functions (serum bilirubin <= 1.5 mg/dl, AST/ALT <= 3 times upper normal limits) * No prior lipid-lowering therapy with statins less than 1 year before study entry * No prior chemo- or immunotherapy for metastatic CRC (adjuvant chemotherapy or chemoradiation therapy more than 6 months before study entry is permitted) * Written informed consent Exclusion Criteria: * Active infection requiring antibiotics therapy * Pregnancy and/or lactation * Other serious illness or medical condition not appropriate for chemotherapy, especially cardiovascular disease * Metastatic brain lesions * Receipt of radiotherapy within 2 weeks before the initiation of study treatment

Study Objectives This is a single-arm, open-label, multicenter, international pilot study to evaluate changes that occur in 2-deoxy-2-\[18F\]fluoro-D-glucose (FDG)- and 3'-deoxy-3'-\[18F\]fluorothymidine(FLT)-PET (Positron Emission Tomography) imaging as a result of treatment with erlotinib in patients with recurrent or refractory non-small cell lung cancer (NSCLC). The study will enroll approximately 30 patients at approximately 4 sites in Australia and 2 sites in the United States. Conditions: Non-Small Cell Lung Cancer Intervention / Treatment: OTHER: 2-deoxy-2-[18F]fluoro-D-glucose (FDG), OTHER: 3'-deoxy-3'-[18F]fluorothymidine (FLT), DRUG: erlotinib HCl Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Signed Informed Consent Form(s) * Histologically confirmed NSCLC * Recurrent or progressive disease after receiving at least one chemotherapy regimen for advanced or metastatic NSCLC * Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 * Age >= 18 years * Recovery from reversible acute effects of prior anti-cancer therapy (chemotherapy, radiotherapy, or investigational treatment) to NCI Common Toxicity Criteria for Adverse Events (NCI CTCAE) Grade <= 1 (excluding alopecia) * Ability to comply with the study and follow-up procedures, including all specified imaging studies * Ability to take oral medication * Availability of archival diagnostic paraffin-embedded tumor tissue and willingness to provide sufficient tissue for testing for EGFR levels in tumor by both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) * Life expectancy >= 3 months * Measurable disease on computed tomography (CT) * At least one detectable lesion on FDG-PET scan and/or FLT-PET scan that is measurable on CT * Use of an acceptable means of contraception (men and women of childbearing potential) or documentation of infertility Exclusion Criteria: * Prior treatment with an investigational or marketed agent for the purpose of inhibiting epidermal growth factor receptor (EGFR) (including, but not limited to, erlotinib and gefitinib) * Chemotherapy, radiotherapy, or investigational treatment within 14 days or within 5 half-lives of the active molecules in the chemotherapy or investigational treatment, whichever is longer, prior to study entry or from which patients have not yet recovered * Inability to take oral medications, disease affecting gastrointestinal absorption, or prior surgical procedure affecting gastrointestinal absorption * Uncontrolled diabetes * Any unstable systemic disease (including active infection, unstable angina, congestive heart failure, myocardial infarction within 1 month prior to study entry, hepatic, renal, or metabolic disease) * Pregnancy or lactation * History of another malignancy in the past 2 years, unless the malignancy has been adequately treated, is currently not detectable, and is associated with a 5-year survival > 90% * Claustrophobia * Any other disease, condition, physical examination finding, or clinical laboratory finding which, in the opinion of the investigator, makes the patient inappropriate for the study

Study Objectives The purpose of this study is to show that Nivolumab will improve progression free survival in subjects with strongly Stage IV or Recurrent PD-L1+ non-small cell lung cancer when compared to chemotherapy Conditions: Stage IV or Recurrent Non-Small Cell Lung Cancer Intervention / Treatment: BIOLOGICAL: Nivolumab, DRUG: Gemcitabine, DRUG: Cisplatin, DRUG: Carboplatin, DRUG: Paclitaxel, DRUG: Pemetrexed Location: Hungary, Canada, Turkey, United States, Greece, Taiwan, Austria, Czechia, France, Poland, Italy, Netherlands, United Kingdom, Finland, Spain, Brazil, Belgium, Sweden, Mexico, Germany, Japan, Korea, Republic of, Romania, Switzerland, Australia, Argentina Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) <= 1 * Histologically confirmed Stage IV, or Recurrent NSCLC with no prior systemic anticancer therapy * Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per response evaluation criteria in solid tumors version (RECIST) 1.1 criteria * PD-L1+ on immunohistochemistry testing performed by central lab * Men and women, ages >= 18 years of age Exclusion Criteria: * Known epidermal growth factor receptor (EGFR) mutations which are sensitive to available targeted inhibitor therapy * Known anaplastic lymphoma kinase (ALK) translocations * Untreated central nervous system (CNS) metastases * Previous malignancies * Active, known or suspected autoimmune disease

Study Objectives Nimotuzumab (hR3) is an IgG1 humanized monoclonal antibody that recognized an epitope located in the extra cellular domain of the human epidermal growth factor receptor (EGFR). Clinical efficacy has been shown in adult with head and neck cancer. The phase I study assessed the safety, and efficacy of the combination of Nimotuzumab administered concomitantly with chemo-radiotherapy in patients with locally advanced esophageal cancer tumours. Conditions: Advanced Esophageal Intervention / Treatment: DRUG: Nimotuzumab Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Informed consent form signed before performing any of the study's specific procedures. * ECOG performance status 0-2. * Age > 18 and < 75. * Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, greater than or equal to 1 cm (longest diameter) by spiral computed tomography (CT) scan and MRI or greater than or equal to 2 cm by other ordinary radiographic technique. * Histologically confirmed diagnosis of locally advanced esophageal. * Life expectancy of more than 3 months. * Use of an effective contraceptive method for patients of both sexes when there is a risk of conception and/or pregnancy. * No serious blood producing,abnormal function of heart,lung, liver, or kidney or immuno-deficiency * Neutrophils >=3×109/L, platelet count>=100×109/L and haemoglobin>=9g/dL ,Creatinine <= 1.5 x NUL Exclusion Criteria: * Previous radiotherapy or chemotherapy * Pregnant or breast-feeding women * Drug abuse, unhealthy drug/alcohol addiction,or virus (HIV) infection * Evidence of distant metastasis * Participation in other clinical trials * Patients with aphthosis, complete obstruction, fistula or deep peptic ulcer in the esophagus, or haematemesis * Uncontrolled psychiatric disease or seizure * Patients not fit for the clinical trial judged by the investigators

Study Objectives This study will examine the safety profile of vadastuximab talirine (SGN-CD33A) by itself (monotherapy) or in combination with other standard treatments. The main purpose of this study is to find the best dose and schedule for SGN-CD33A when given in combination with standard induction treatment, in combination with standard consolidation treatment, or by itself for maintenance treatment. This will be determined by observing the dose-limiting toxicities (the side effects that prevent further increases in dose) of SGN-CD33A. In addition, the pharmacokinetic profile and anti-leukemic activity of the study treatment will be assessed. Conditions: Acute Myeloid Leukemia, Acute Myelogenous Leukemia Intervention / Treatment: DRUG: Standard dose cytarabine for induction, DRUG: SGN-CD33A, DRUG: Daunorubicin, DRUG: High dose cytarabine for consolidation Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * All subtypes of Acute Myeloid leukemia (except for acute promyelocytic leukemia) * Eastern Cooperative Oncology Group status of 0 or 1 * Adequate baseline renal and hepatic function * Central venous access * Part specific requirements: eligible to receive induction; achieved CR/CRi with standard induction and eligible to receive consolidation; in CR with documented blood count recovery for maintenance Exclusion Criteria: * Previous treatment for MDS or MPN for dose escalation cohorts * Inadequate lung function * Inadequate heart function

Study Objectives The purpose of this study is to evaluate the effect of administration of low dose of human chorionic gonadotropin (HCG) after use of clomiphene citrate (CC) for induction of ovulation in infertile women having CC resistant polycystic ovarian syndrome (PCOS). Conditions: Infertility, Polycystic Ovarian Syndrome Intervention / Treatment: DRUG: Clomiphene citrate and Human chorionic gonadotropin (HCG), DRUG: Clomiphene citrate Location: Egypt Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Infertile lean women with PCOS as defined by the Rotterdam criteria. * CC resistance (defined as failure of ovulation after receiving 150 mg/day of CC for 5 consecutive days per cycle, for at least 3 consecutive cycles). Exclusion Criteria: * Age < 20 or > 35 years. * Presence of any infertility factor other than anovulatory PCOS. * Previous history of ovarian surgery or surgical removal of one ovary. * Previous exposure to cytotoxic drugs or pelvic irradiation. * Oral hypoglycemic or hormonal therapy either currently or in the preceding 3 months. * Metabolic or hormonal abnormalities.

Study Objectives The purpose of this Phase I study is to find the largest dose of the drug irinotecan, in combination with ZD1839, that can be given safely to children and to learn the good and bad effects. Studies performed in the laboratory have shown that ZD1839 helps make available the orally administered irinotecan. In this study the intravenous (given into the vein) formula of irinotecan will be given orally on days 1-5 and days 8-12. The dose of ZD1839 will be a fixed dose and will be administered orally on days 1-12. Each course of treatment will consist of 21 days. The administration of irinotecan on day 12 of course 1 and day 2 of course 2 will be an intravenous administration. All other doses and subsequent courses will consist of an orally administered dose. Conditions: Glioblastoma, Rhabdomyosarcomas, Neuroblastoma, Osteosarcoma Intervention / Treatment: DRUG: Irinotecan (Camptosar), Gefitinib (Iressa) 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: * Patient's age is less than or equal to 21 years at the time of study entry. * Patient has a histologically or pathologically confirmed diagnosis of a recurrent solid tumor that did not respond to standard treatment or one for which there is no known therapy. * Patient has adequate performance status, along with adequate function of the liver, kidney and bone marrow. * Must have recovered from chemotherapy * No active GVHD nor treatment for GVHD Exclusion Criteria: * Patient is receiving other cytotoxic or investigational drug or has evidence of another active illness * Active diarrhea * Active intercurrent serious or uncontrolled illness * Pregnant or lactating * Concomitant use of medications that may interact with study drugs * Active infection * Known history of life-threatening allergy or hypersensitivity to camptothecin Active interstitial lung disease

Study Objectives This study is a phase I, open-label, single-arm, dose escalation trial to determine the safety and activity of lenalidomide combined with lintuzumab in patients with MDS. Small groups of 3-6 patients will be treated with pre-specified doses of lenalidomide and lintuzumab and will receive 3-week cycles of combination therapy. Conditions: Myelodysplastic Syndrome (MDS) Intervention / Treatment: DRUG: lintuzumab, DRUG: lenalidomide Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Disease confirmation of MDS. * Between 5% and 30% blasts in the bone marrow. * Received treatment for cytopenias within 2-months * ECOG <= 2. Exclusion Criteria: * Received prior therapy with lenalidomide, gemtuzumab ozogamicin (Mylotarg®). * Received chemotherapy/radiotherapy within 4 weeks of study registration. * Received prior bone marrow transplant. * 5q- chromosomal deletion in malignant cells.

Study Objectives The primary objective of this study was to determine the safety, tolerability, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of CHR-2797 when administered orally, once daily, to patients with advanced solid tumours. The secondary objectives of this study were: * To determine pharmacokinetic parameters for CHR-2797 when administered orally at increasing dose levels; * To investigate the pharmacodynamic effects of CHR-2797 in blood mononuclear cells and, when possible, tumour cells; - To enable a preliminary assessment of anti-tumour activity of CHR-2797. Conditions: Advanced Solid Tumors Intervention / Treatment: DRUG: CHR-2797 (tosedostat) Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Signed, informed consent * Histological or cytologically confirmed malignant solid tumour refractory to standard therapy or for which no standard therapy exists * Evaluable disease * Recovered from the acute adverse effects of prior therapies (excluding alopecia and grade 1 neuropathy) * Adequate bone marrow, hepatic and renal function including the following: 1. Hb >= 9.0 g/dl, absolute neutrophil count >= 1.5 x 109/L, platelets >= 100x109/L 2. Total bilirubin <= 1.5 x upper normal limit 3. AST and ALT <= 2.5 x upper normal limit (or <= 5 x UNL in the presence of liver metastases) 4. Creatinine <=1.5 x upper normal limit * Age < 18 years * Performance status (PS) < 2 (ECOG scale) * Estimated life expectancy greater than 3 months * Female patients with reproductive potential had to have a negative serum pregnancy test within 7 days of treatment. Both women and men had to agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months after discontinuation of treatment. Acceptable methods of contraception included IUD, oral contraceptive, sub-dermal implant and double barrier (condom with a contraceptive sponge or contraceptive pessary) Exclusion Criteria: * Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the 4 weeks prior to study entry (or a longer period depending on the defined characteristics of the agents used e.g. 6 weeks for mitomycin or nitrosourea). In patients with progressive disease (PD), continuation of LHRH agonists for prostate cancer, bisphosphonates for bone disease and corticosteroids was permitted provided the dose was stable before and during the study * Co-existing active infection or serious concurrent illness * Significant cardiovascular disease as defined by 1. History of congestive heart failure requiring therapy 2. History of unstable angina pectoris or myocardial infarction up to 6 months prior to study entry 3. Presence of severe valvular heart disease 4. Presence of a ventricular arrhythmia requiring treatment * Any co-existing medical condition that in the Investigator's judgement substantially increased the risk associated with the patient's participation in the study * Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies * Gastrointestinal disorders that might have interfered with absorption of the study drug * Persistent grade 2 or greater toxicities from any cause * Patients with known brain tumours or metastases should have been excluded from this clinical study because of their poor prognosis and because they often develop progressive neurologic dysfunction that would have confounded the evaluation of neurologic and other AEs * Pregnant or breast-feeding women

Study Objectives Study Objectives: * To determine the MTD (maximal tolerated dose) and recommended dose of a weekly docetaxel and cisplatin combination regimen for locoregional recurrent/metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) * To determine the response rate of the recommended dose * To determine the safety and tolerability of the recommended dose Conditions: Head and Neck Neoplasms Intervention / Treatment: DRUG: Docetaxel Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed (of original primary tumor) locoregional recurrent and/or metastatic following prior radiotherapy and/or surgery and not amenable to further curative local therapy for SCCHN * Measurable disease as defined by at least the longest diameter measured as 20 mm by conventional CT or 10 mm by spiral CT. Physical measurements are allowed if longest diameter is 20 mm by caliper measurements. * ECOG performance status 0-2 * Adequate bone marrow and hepatic function as evidenced by the following: * Hematology (Bone marrow): * Neutrophils >= 1.50 x 10^9/L * Platelets >= 100 x 10^9/L * Hemoglobin >= 10 g/dL * Hepatic function: * AST and/or ALT: < 2X ULN (Upper Limit of Normal) * Bilirubin < 1X ULN * Adequate renal function with calculated or measured glomerular filtration rate of > 60 ml/min calculated by the Cockcroft- Gault method * No severe intercurrent illness or other serious illness or medical conditions including but not limited to: * Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry. * Active uncontrolled infection * Active peptic ulcer * Chronic obstructive pulmonary disease requiring hospitalization during the year preceding study entry * No prior chemotherapy for recurrent/advanced SCCHN with platinum or taxane regimen (primary radiosensitizing platinum allowed). * No other diagnosed malignancy other than basal cell carcinoma of the skin or cervix carcinoma in situ Exclusion Criteria: * Prior therapy with taxanes either adjuvant, neoadjuvant, concurrent or in advanced stage disease * Prior chemotherapy for locoregional recurrent/metastatic SCCHN with palliative intent * Contraindications from * the medical history (i.e. known hepatitis, HIV) and physical exam * laboratory tests (hematology, biochemistry) * 12-lead electrocardiogram * blood pressure and pulse * Pregnancy * Breast-feeding * Treatment with any investigational product in the last 4 weeks before study entry * Likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol * Presence or sequelae of gastrointestinal, liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs * History of hypersensitivity to the study drug(s) or to drugs with a similar chemical structure * Impaired hepatic function, as shown by bilirubin greater than upper limits of normal and/or AST greater than 2 times upper limits of normal * Impaired renal function, as shown by measured or calculated creatinine clearance of < 60 ml/min or absolute creatinine level > 1.5 upper limit of normal

Study Objectives To learn whether Flourine-18 Fluoro-deoxi-glucose positron emission tomography / computed tomography (F-18 FDG PET/CT) and dynamic contrast enhanced magnetic resonance imaging (DCE MRI) are better predictors of response to therapy than the current standard of care (CT or MRI). Conditions: Kidney Neoplasms, Carcinoma, Renal Cell, Kidney (Renal Cell) Cancer Intervention / Treatment: PROCEDURE: FDG PET CT, PROCEDURE: DCE MRI, DRUG: F-18 Fluoro-deoxi-glucose, DRUG: Gadolinium-DTPA, DRUG: Sunitinib Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: DIAGNOSTIC Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria:- Measurable disease by RECIST criteria * Pathologic diagnosis of renal cell cancer * Advanced (stage IV) renal cell cancer * Karnofsky performance status of (KPS>70) * Consent to participate in the clinical trial Exclusion Criteria:- Patients who cannot complete a PET/CT scan. * Pregnant women. * Healthy volunteers. * Patients participating in other research protocols will be excluded from this study. * Metallic implants (prosthesis, ICD, pacemakers), since these are contraindications for MRI.

Study Objectives The purpose of this open-label, multi center, Phase I study was to determine the safety profile of the oral compound PHA-848125AC administered according to two different schedules of administrations to advanced/metastatic solid tumor patients. Objectives of the study were to determine the maximum tolerated dose and the dose that can be recommended for Phase II investigations. Conditions: Solid Tumour Intervention / Treatment: DRUG: PHA-848125AC Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Signed, written IRB-approved Informed Consent * Histologically or cytologically confirmed relapsed or refractory solid tumors for which no standard therapy exists * ECOG (WHO) performance status 0-1 * Life expectancy of at least 3 months * Age >=18 years * A negative pregnancy test (if female in reproductive years) * Acceptable liver and renal function * Acceptable hematologic status * 10. Previous cancer therapy is allowed with the exclusion of experimental CDK2 inhibitors. Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy must be completed within one month prior to study entry * Use of effective contraceptive methods if men and women of child producing potential * Capability to swallow capsules intact * Grade <=1 retinopathy Exclusion Criteria: * In the past 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis * Known brain metastases * Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1 * Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy * Pregnant or breast feeding women * Unwillingness or inability to comply with procedures required in this protocol * Known infection with HIV, active hepatitis B or hepatitis C * Diabetes mellitus uncontrolled, or with clinical evidence of diabetic retinopathy, severe peripheral vascular disease or diabetic ulcers * Current enrollment in another clinical trial * Patients who have exhibited allergic reactions to a similar structural compound, biological agent, or formulation (lactose intolerance) * Previous history or current presence of neurological disorders, including epilepsy (although controlled by anticonvulsant therapy), Parkinson's disease, multiple sclerosis, stroke and cerebellar injury * Gastrointestinal disease (e.g. Crohn's disease, ulcerative colitis, or short gut syndrome) that would impact on drug absorption * Chronic/intensive use of antacid or H2 receptor antagonists * Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation 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 or could compromise protocol objectives in the opinion of the investigator and/or the sponsor.

Study Objectives The aim of the study is to evaluate the safety/tolerability, pharmacokinetic, and pharmaco-dynamic effects of KA2507 and establish the maximum tolerated dose (MTD). Patients with PD-L1 expressing solid tumors which have relapsed or are refractory to prior treatment will be eligible to participate in this study. Following completion of the multiple ascending dose study, the protocol may be amended to include expansion cohorts in patients with melanoma and/or other solid tumors. Conditions: Solid Tumor, Adult Intervention / Treatment: DRUG: KA2507 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: * Age >=18 years at the screening visit. * Patients with histologically or cytologically documented, confirmed diagnosis of advanced malignancy, whose disease failed to respond to or progressed after standard therapy or they could not tolerate standard therapy. * Measurable or evaluable disease according to RECIST v1.1. * ECOG performance status of 0 or 1. * Predicted life expectancy >=12 weeks. * For men and women of child-bearing potential, willing to use adequate contraception (i.e., latex condom, cervical cap, diaphragm, abstinence, etc.) for the entire duration of the study. * If female, must be either postmenopausal, sterilised or, if sexually active, effectively practicing an acceptable method of contraception (either oral, parenteral, or implantable hormonal contraceptives, intrauterine device or barrier and spermicide). Subjects must agree to use adequate contraception during the study and for at least 12 weeks (or longer as per local requirement) after the last dose of study treatment. * Male subjects agree to ensure that they or their female partner(s) use adequate contraception during the study and for at least 12 weeks (or longer as per local requirement) after the subject receives their last dose of study treatment. Exclusion Criteria: * Patients are not able to provide written informed consent to study participation * Patients who have been treated with most recent radiotherapy, hormonal therapy, immunotherapy, chemotherapy or investigational drugs within <=21 days or 5 half-lives (whichever is shorter) from enrolment (screening), and/or who have any unresolved NCI Common Terminology Criteria of Adverse Events (CTCAE) v4.03 > Grade 1 treatment-related side effect (with the exception of alopecia). * Patient has anemia due to HbS or HbC disease, alpha or beta thalassaemia * Patient has Glucose-6-phosphate deficiency * Patient has known or suspected history of cytochrome b5-MetHb-reductase pathway deficiency * Persons of Navajo, Athabaska Alaskan or Siberian Yakutsk descent * Patient has untreated severe hypothyroidism * Patient has laboratory estimations indicating organ system dysfunction: 1. Absolute neutrophil count (ANC) <1.5 X 109/L 2. Platelets <100 X 109/L 3. Hemoglobin <9g/dL 4. Total bilirubin >1.5 mg/dL 5. ALT and AST >3.0 times the ULN if no liver involvement or >5 times the ULN with liver involvement. 6. Calculated creatinine clearance <60mL/min estimated using the Cockcroft-Gault equation: * Cockcroft-Gault equation: creatinine clearance = (140 - age in years) x (wt in kg)) x 1.23) / (serum creatinine in micromol/l) [For women multiply the result of calculation by 0.85]. * Major surgery (excluding placement of vascular access) <=21 days from beginning of the study drug or minor surgical procedures <=7 days. No waiting is required following implantable port and catheter placement. * Any of the following cardiac criteria: 1. Congestive heart failure (CHF), grade III or IV per New York Heart Association (NYHA) classification 2. Symptomatic cardiomyopathy 3. > Class II Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy 4. Unstable angina or new-onset angina 5. QTcF interval >470 ms on screening ECG. * Severe or uncontrolled systemic diseases including uncontrolled hypertension, active bleeding diatheses 10. Any evidence of active infection including active Hepatitis B, Hepatitis C or human immunodeficiency virus 11. The patient has concurrent severe and/or uncontrolled medical disease that could compromise participation in the study (i.e., uncontrolled diabetes, severe infection requiring active treatment, severe malnutrition, chronic severe liver or renal disease, uncontrolled hypertension, active bleeding diatheses). * Active infection requiring IV antibiotics within two weeks prior to treatment, or evidence of TB infection. * Hepatitis B, Hepatitis C or human immunodeficiency virus 14. Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 3 weeks previously and there is no evidence of central nervous system disease progression, mild neurologic symptoms, and no requirement for chronic corticosteroid therapy. * Lactating, breastfeeding, or positive pregnancy test for female patients of child-bearing potential. * The patient is unable to swallow capsules and/or has a surgical or anatomical condition that precludes swallowing and absorbing oral medication on an ongoing basis (for oral therapy only). * Patients with prior stem cell transplantation or solid organ transplantation. * History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 3 years. * Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.

Study Objectives The purpose of this study is to determine whether prophylaxis with micafungin is effective in the induction chemotherapy for newly diagnosed acute leukemia patients. Conditions: Acute Leukemia Intervention / Treatment: DRUG: Micafungin Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: PREVENTION Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: A. patients belong to either A-1 or A-2 A-1. patients with newly diagnosed acute myeloid leukemia who approve to get induction chemotherapy with (cytarabine plus idarubicin) or (modified Fludarabine + cytarabine + idarubicin ) A-2. patients with newly diagnosed acute lymphoid leukemia who approve to get induction chemotherapy with VPDL (vincristine + prednisolone + daunorubicin + L-asparaginase), C-VPDL (cyclophosphamide + vincristine + prednisolone + daunorubicin + L-asparaginase), or (R)-hyperCVAD ((Rituximab) + cyclophosphamide + vincristine + Adriamycin + dexamethasone) B. Eastern Cooperative Oncology Group performance status score is equal to or more than 2 C. patients who voluntarily sign the agreement Exclusion Criteria: A. evidence of proven/probable/possible fungal infection within 30 days before induction chemotherapy B. hypersensitivity to echinocandin C. patients had other malignancy within 5 years D. previous treatment history with chemotherapy, radiation therapy, or immunosuppressive therapy. E. pregnant or breast-feeding women F. immunodeficient patients including AIDS G. patients with uncontrolled seizure or psychiatric disorder H. clinically significant heart disorder (myocardial infarction within 3 months or left ventricular ejection fraction < 40%) I. interstitial lung disease J. previous organ transplantation history K. galactose intolerance L. patients who participated this study before.

Study Objectives Despite certain notable progress, treatment of patients with Chronic Lymphatic Leukemia (CLL) is still disappointing. Although thanks to the use of treatment of (immune) chemotherapy, mainly based on fludarabine, rituximab and alemtuzumab, the rate of complete response (CR) has increased from minus 10% observed when clorambucil was the core of the therapy to a 60-70%, with time all patients relapse and most of them die at the end due to the disease or to involvements related to the treatment. Progress when understanding the CLL biology have cleared a series of aspects: 1) there is a significant proportion of CLL cells actively copying themselves, contrary to the opinion that most of CLL cells are in G0 phase of the cell cycle; 2) Immune regulatory mechanism basically measured by T cells and NK cells have an important role in the continuous accumulation of CLL cells in the body; 3) Cells of the stroma are essential to maintain survival of CLL cells through a series of cytokines or chemokines. Under the light of this evidence, it is worth studying new treatment modes directed not only to CLL cells but also to the microenvironment and immune functions. Lenalidomide is being investigated as treatment for several oncologic indications including myelodysplastic syndromes, multiple myeloma and non-Hodgkin lymphoma. Within the scope of CLL, it has been proved that lenalidomide is active in patients with relapsing / treatment resistant CLL patients. Forty five patients with relapsing CLL, 51% resistant to fludarabine, where included in a phase II study and were treated orally with 25 mg of lenalidomide on days 1 to 21 of a cycle of 28 days. The total response rate was of 47% with up to a 9% of complete responses. The combination of lenalidomide with dexamethasone is being investigated in multiple myeloma and has revealed as a highly efficient treatment in relapsing/ treatment resistant patients as well as in those newly diagnosed. Bearing in mind that both drugs, lenalidomide and dexamethasone, are clinically active in CLL the investigators have designed a study with this combination in relapsing or treatment resistant patients following treatments containing fludarabine which do not meet the requirements for an intensive rescue treatment. Given initial doses of 10 and 25 mg of lenalidomide daily may be associated with tumor lysis cases, it is proposed a low initial dose of lenalidomide in the first cycle 2.5mg., with further increases to prevent the occurrence of tumor lysis syndrome Conditions: Chronic Lymphatic Leukemia Intervention / Treatment: DRUG: Lenalidomide, DRUG: Dexamethasone Location: Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: The patients will have to meet the following inclusion criteria in order to be included in the study: * To understand and voluntarily sign an informed consent form. * To be >= 18 years old upon the signature of the informed consent form. * To be able to fulfill the visits program of the study and other protocol requirements. * To have a CLL documented diagnose (NCI/WG criteria) relapsing or resistant to at least one prior treatment and not to meet the requirements for an intensive rescue therapy. Prior treatment(s) will have to include fludarabine. * All prior anti-cancer therapies, including radiation, hormonal therapy and surgery, will have to be interrupted at leas 4 weeks before the treatment in this study. * Functional state 0-2 (ECOG). * Women with childbearing potential (FCBP) will have to: understand the teratogenic risk of the study drug. accept the simultaneous use of two reliable contraception methods or to practice the abstinence of heterosexual relations during the following periods of time related to this study: 1) during at least 4 weeks before starting the drug of the study; 2) while participating in the study; y 3) during at least 4 weeks following the interruption of the study. The two reliable contraceptive methods will have to include one highly effective (this is, intrauterine device (IUD), hormonal (pills injections or implants), tubal ligation, vasectomy of the partner) and an barrier effective additional method (this is, latex preservative, diaphragm, cervical cap). Women with a childbearing potential will have to visit a specialist in contraceptive methods if necessary. Before starting the drug under study: * Women with childbearing potential will have to undergo two negative pregnancy tests (sensibility of at least 25 mUI/ml) before starting the drug under study. The first test will take place at the visit date or within a period of 3 days before starting the drug under study and the second.The patient will not receive the drug until the investigator has verified that the results of the tests are negative. Men: * They will have to accept the use of latex preservatives during sexual relations with women with childbearing potential while they participate in the study and during at least one week following the interruption of the study, if it is women with childbearing potential (FCBP) and no use contraception. * They will have to accept to refrain from donating blood or semen during their participation in the study and during at least 28 days following the interruption of the study. * In the event of pregnancy or positive pregnancy test in a participant in the study, or the partner of a male participant in the study, during his participation, the drug under study will be immediately interrupted. * Capable of receiving Acetyl Salicylic Acid (100 or 300 mg) on a daily basis as prophylactic anticoagulation. (Patients who do not tolerate ASA may use acenocumarol or low molecular weight heparin). Exclusion Criteria: Patients will not have to fulfill any of the following exclusion criteria to be included in the study. * Any serious medical disorder, laboratory abnormality or psychiatric disease hindering the signature of the informed consent by the patient. * Pregnant women or in lactation period. * Any disorder, including the presence of laboratory abnormalities, which puts the patient at unacceptable risk if he/she participates in the study or hindered the capacity to understand the information of the study. * Use of any other experimental drug or therapy in the period of 28 days from the base visit. * Known hyper-sensibility to thalidomide. * Development of erythema nodosum if it is characterized by a descamative eruption while taken thalidomide or similar drugs. * Any prior use of lenalidomide. * A concurrent use of other agents or anticancer treatments. * HIV-positive or infectious hepatitis type A, B or C. * Candidates eligible for intensive rescue therapies (ex. R-CHOP plus alemtuzumab, allogenic transplant) * Richter transformation (active) or CNS participation (active) * Any of the following laboratory abnormalities: Neutrophil absolute count < 0.5 x 109/L Platelet count < 25 x 109/L Calculated Creatinine Clearance <50 mL/min Total serum bilirubin > higher normal limit (HNL) AST and ALT >3 x higher normal limit (HNL) Autoimmune non controlled hemolytic anemia or thrombocytopenia. * History of another neoplastic disease during >= 5 years unless base cells or epidermoid carcinoma in situ of cervix or breast recently treated.

Study Objectives Nimotuzumab (hR3) is an IgG1 humanized monoclonal antibody that recognized an epitope located in the extra cellular domain of the human epidermal growth factor receptor (EGFR). Clinical efficacy has been shown in adult with head and neck cancer. The phase II study assessed the efficacy and safety of the combination of Nimotuzumab administered concomitantly with radiotherapy in patients with esophageal cancer tumours. Conditions: Esophageal Intervention / Treatment: DRUG: Nimotuzumab, RADIATION: Radiotherapy Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * pathologically or cytology diagnosed phase II-III esophageal carcinoma or IV thoracic segments carcinoma with the supraclavicular lymph nodes metastasis. * with the measureable lesion of the newly diagnosed the esophageal carcinoma. * age 18-75 years old * ECOG<=2 * Expect survival date >=3 months * without serious diseases of important organs * signature in the inform consent. Exclusion Criteria: * pregnant or breast-feeding women or using a prohibited contraceptive method. * with psychiatric diseases. * with serious diseases or uncontrolled infection. * with history of other tumors. * participation other clinical trials within 1 month prior to inclusion in the trial. * not the first antitumor treatment .

Study Objectives Based on preclinical data, ZD1839 is considered a novel and promising therapeutic approach with potential application in the treatment of human breast cancer. Therefore it could be very important and clinically relevant to know if ZD1839 is capable of eliminating occult tumour cells circulating in the blood of breast cancer patients Conditions: Breast Cancer Intervention / Treatment: DRUG: ZD1839 Location: Greece Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Provision of written informed consent * Histologically or cytologically confirmed breast cancer * Metastatic breast cancer (stage IIIB and IV) * Patients should have received at least one course of standard systemic chemotherapy for their metastatic disease. There should be at least one month between end of chemotherapy treatment and trial entry. * ER+ve patients should have received adjuvant hormonal treatment * Detection of CK-19 mRNA positive cells in the blood by real time PCR despite the previous administration of chemotherapy and if appropriate hormonal therapy * Aged 18 years and over * Paraffin-embedded tissue available for tumour histology (EGFR testing, ER, PgR, Her-2-neu testing) * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2 * Patients willing to undergo regular detection of circulating occult tumour cells in the blood by immunocytochemistry and/or RT-PCR * Life expectancy of at least 12 weeks Exclusion Criteria: * Any concurrent systemic treatment for breast cancer (including chemotherapy, radiotherapy, hormonotherapy, monoclonal antibodies) * Known severe hypersensitivity to ZD1839 or any of the excipients of this product * Any evidence of clinically active interstitial lung disease (patients with chronic, stable, radiographic changes who are asymptomatic need not be excluded) * Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ * Any unresolved chronic toxicity greater than common toxicity criteria (CTC) grade 2 from previous anticancer therapy (except alopecia) * Serum bilirubin greater than 1.5 times the upper limit of reference range (ULRR) * As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease) * Alanine amino transferase (ALT) or aspartate amino transferase (AST) greater than 3 times the ULRR. * Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the study * Pregnancy or breast feeding (women of child-bearing potential). Women of childbearing potential must practice acceptable methods of birth control to prevent pregnancy * Concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St John's Wort * Treatment with a non-approved or investigational drug within 30 days before Day 1 of study treatment

Study Objectives This is a Phase I, multi-centre, open-label, cross-over pharmacokinetic study designed to investigate whether the co-administration of a fixed dose of tesmilifene alters the plasma pharmacokinetics of a standard regimen of epirubicin and/or its principle metabolite, epirubicinol and cyclophosphamide. Conditions: Metastatic/Recurrent Breast Cancer Intervention / Treatment: DRUG: Tesmilifene (YMB 1002) Location: Ukraine, Russian Federation, Georgia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with documented histological/cytological proof of metastatic and/or recurrent breast cancer suitable for treatment with epirubicin and cyclophosphamide. Patients with locally advanced and inoperable lesions are also eligible. * Previous therapy: * If patients have had hormone-responsive disease, randomization is permitted after 6 weeks off anti-hormonal therapy or 5 half lives (whichever is shorter) unless there is evidence of progressive disease in which case patients could be randomized earlier. * No previous exposure to anthracycline/anthracenedione-based chemotherapy. * Patients may have received non-anthracycline/anthracenedione based adjuvant chemotherapy, completed a minimum of 4 weeks prior to randomization. Patients must not have had previous chemotherapy for metastatic disease. * Immunotherapy and experimental therapy must stop a minimum of 4 weeks prior to randomization. * A minimum of four weeks must have elapsed between the end of prior radiotherapy and randomization. Exceptions will be made, however, for palliative radiotherapy which involves no more than 30% of bone marrow. * ECOG status of 0, 1 or 2. * Female, aged 18 to 55 years. * Life expectancy of at least 6 months. * Patients must be willing and able to follow instructions and make all required study visits. * Patients must be willing and able to give written consent to participate in this study. * Disease free interval less than or equal to 36 months. * Normal organ and marrow function * Negative serum or urine pregnancy test within 72 hours prior to randomization and must be on a medically recognized form of birth control that is approved by the investigator. * Negative blood tests for HIV and Hepatitis B and C within 4 weeks prior to randomisation. Exclusion Criteria: * Previous malignancies, excluding curatively treated basal or squamous cell carcinoma of the skin or in-situ cervical cancer or any other cancer treated more than five years prior to study entry and presumed cured. * Known brain or meningeal metastases * Use of chemotherapeutic agents for any malignancy within 4 weeks prior to study entry or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. * Treatment with any other investigational drug within the preceding four weeks. * Pregnant and breast-feeding females. * History of seizure disorder. * Clinical evidence of congestive heart failure, recent myocardial infarction within 6 months, uncontrolled arterial hypertension, unstable angina, cardiomyopathy or arterial or ventricular clinically significant arrhythmias even if medically controlled. * Clinically significant cardiovascular, pulmonary, renal, endocrine, hepatic, respiratory, neurologic, psychiatric, immunologic, gastrointestinal, haematologic, metabolic or any other condition or laboratory abnormality that, in the opinion of the Investigator or Medical Director of YM BioSciences Inc., makes the patient unsuitable for participation in the study. * Known allergy or hypersensitivity to test article ingredients. * Patients on COX 1 or 2 prostaglandin inhibitors (e.g. ASA, other NSAID's, Celcbrex®, Vioxx® ) who can not comply with guidelines or concomitant therapy. * Patients on H1 antagonists as detailed in the protocol who can not comply with guidelines or concomitant therapy

Study Objectives This randomized, open-label, two-way crossover study will evaluate the relative bioavailabilty and safety of capecitabine rapid disintegrating tablets (RDT) versus commercial Xeloda tablets in patients with colorectal or breast cancer. Patients will be randomized to a sequence of single oral doses of capecitabine RDT or Xeloda on Days 1 and 2 of a 14-day treatment cycle with Xeloda. Follow-up will be 30 days. Conditions: Breast Cancer, Colorectal Cancer Intervention / Treatment: DRUG: capecitabine RTD, DRUG: capecitabine [Xeloda], DRUG: capecitabine [Xeloda] Location: Australia, New Zealand, United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * Adult patients,>= 18 years of age * Histological/cytological confirmation of colorectal or breast cancer * Patient is ambulatory and has a Karnofsky performance status of > 70% * Body surface area between 1.5 and 2.0 m2 * Either: * Due to receive Xeloda as monotherapy or as combination therapy as per their treating physician's treatment plan, or * Currently receiving Xeloda monotherapy and in the investigator's opinion able to tolerate study drug dose on Day 1 and Day 2 Exclusion Criteria: * Any contraindication to Xeloda * Received Xeloda in the 6 days prior to Day 1 * Subjects with organ allografts (other than autologous bone marrow transplant after high dose chemotherapy) * Renal impairment * Pregnant or lactating females * Participation in an investigational drug study within 28 days prior to screening * Lack of physical integrity of the upper gastrointestinal tract, or clinically significant malabsorption syndrome * Serious uncontrolled intercurrent infections * History of clinically significant coronary artery disease * Concomitant treatment with warfarin * Known dihydropyrimidine dehydrogenase deficiency

Study Objectives Phase 1A/B, multicenter, open-label, non-randomized, dose-escalation oncology study to evaluate the administration of EC1456 in advanced solid tumors. In part A, EC1456 will be dose escalated on 4 concurrently enrolling schedules. FR-positive expression on a 99mTc-etarfolatide scan is not required for inclusion in Part A. Part B of the study will confirm the maximum tolerated dose (MTD) and the recommended Phase 2 (RP2) dose of EC1456, and evaluate the efficacy of EC1456 in NSCLC all subtype patient populations with FR-positive cancer in up to three schedules (i.e., twice weekly, once weekly, and four times weekly). FR-positive expression on a 99mTc-etarfolatide scan is required for inclusion in Part B. Minimum length of patient participation is anticipated to be 10 weeks (two 3-week cycles followed by a 30 day follow-up period). Conditions: Solid Tumors, Non Small Cell Lung Carcinoma Intervention / Treatment: DRUG: EC1456 and EC20 Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: Patients enrolled in Part A must receive the 99mTc- etarfolatide scan but they do not need to have FR-positive target lesions. Parts A and B: To qualify for enrollment, the following criteria must be met: * Patient must have the ability to understand and sign an approved informed consent form (ICF). * Patient must be >= 18 years of age. * Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Patient must have a life expectancy of > 3 months. * Patient must have at least one measurable lesion per RECIST v1.1 Criteria as assessed on baseline radiologic evaluation obtained no more than 28 days prior to beginning study therapy. * Patients with central nervous system (CNS) metastases that are symptomatic must have received therapy (e.g., surgery, XRT, gamma knife, etc.) and be neurologically stable and off of steroids. The patient should be off steroids at least 14 days before registration. Patients with asymptomatic CNS metastatic disease without associated edema, shift, and a requirement for steroids or anti-seizure medications may be eligible after discussion with the sponsor medical monitor. * Patients must have formalin fixed tissue (biopsy or FNA) available. * Patient must have recovered (to baseline/stabilization) from prior chemo or radio therapy and associated acute toxicities must have resolved to a NCI CTCAE V4 Grade 1 or less, with the exception of alopecia. * Patients treated with prior radiation therapy may be eligible if: 1. Radiotherapy was completed at least 2 weeks before first dose of EC1456 and 2. Patient has recovered from acute radiation toxicity. * Patients must have adequate organ function: 1. Bone marrow reserve: Absolute neutrophil count (ANC) >= 1.5 x 109/L; Platelets >= 100 x 109/L; Hemoglobin >= 9 g/dL. 2. Cardiac: i. QTcFridericia (QTcF) < 450 msec on at least 2 of 3 screening ECG's. On site determination of QTcF may be used for screening purposes. ii. Left ventricular ejection fraction (LVEF) equal to or greater than the institutional lower limit of normal. LVEF must be evaluated within 28 days prior to C1D1. iii. Cardiac Troponin I or T within normal limit. (whichever troponin is done for screening will need to be done throughout the rest of the study). c. Hepatic: Total bilirubin <= 1.5 x the upper limit of normal (ULN); Alanine aminotransferase (ALT), aspartate aminotransferase (AST) <= 3.0 x ULN OR <= 5.0 x ULN for patients with liver metastases. d. Renal: Serum creatinine <= 1.5 x ULN or for patients with serum creatinine > 1.5 ULN, creatinine clearance >= 50 mL/min. Patients of childbearing potential: * All women of childbearing potential MUST have a negative urine or serum pregnancy test within 1 week prior to the 99mTc-etarfolatide imaging procedure and within 1 week prior to treatment with EC1456. * Women of child bearing potential must practice an effective method of birth control (i.e., oral, transdermal or injectable contraceptives, intrauterine device [IUD], or double-barrier contraception, such as diaphragm and spermicidal jelly) for the duration of their participation in the trial through 90 days following the last dose of EC1456. * Male patients who are sexually active must practice an effective method of birth control (e.g., condom and spermicidal jelly) for the duration of their participation in the trial through 90 days following the last dose of EC1456. Patient and Disease Specific Inclusion Criteria: Part A EC1456 dose escalation cohorts (Treatments 1, 2, 3, and 4): * Patients must have pathologically confirmed metastatic or locally advanced solid cancer (preferably TNBC, NSCLC, ovarian, or endometrial cancers due to frequent high FR expression in these cancers) that has failed to respond to standard therapy, is not amenable to standard therapy, or for which standard therapy does not exist. * TNBC and ovarian patients must agree to submit results of BRCA 1/2 status (i.e., deleterious mutation present, mutation of unknown significance, no mutation detected) if known. BRCA testing is not required for study inclusion. * Patients must have received <= 4 prior lines of systemic anti-cancer therapy (including but not limited to cytotoxic agents, targeted inhibitors, and monoclonal antibodies). Hormonal therapies are not included toward this criterion. * Patients must undergo a 99mTc-etarfolatide SPECT imaging procedure in compliance with the Investigator's Imaging Operations Manual (IIOM). FR expression on 99mTc -etarfolatide SPECT is not required for inclusion in Treatments 1, 2, 3, and 4. (Patients who underwent a 99mTc-etarfolatide SPECT/CT imaging procedure as a subject on Endocyte study EC20.12 will not be required to have a repeat scan for participation in study EC1456-01 if the scan was obtained within 4 weeks of cycle 1 day 1 of EC1456 administration and has been deemed acceptable by Endocyte Imaging.) Part B Only: Patient and Disease Specific Inclusion Criteria: Part B Patients with FR-positive NSCLC (all subtypes): (Treatments 5, 6, and 7) * Patients with NSCLC (all subtypes) must have received one prior platinum based therapy for advanced or metastatic disease. No additional cytotoxic therapy for advanced or metastatic disease is allowed. Any number of prior targeted therapies (e.g., inhibitors of ALK, EGFR, and PD-1 or PD-L1) are allowed. Patients with known relevant genomic tumor aberrations (i.e., EGFR, ALK, ROS-1, etc) must have received and progressed on approved therapy for these aberrations. This information must be documented prior to study entry. * Patients must undergo a 99mTc-etarfolatide SPECT imaging procedure in compliance with the Investigator's Imaging Operations Manual (IIOM) and be FR-positive. Exclusion Criteria: Parts A and B: The presence of any of the following will exclude patients from the study: * Systemic anti-cancer treatment, except hormonal treatment, within 28 days prior to EC1456 administration unless there are no remaining or ongoing uncontrolled toxicities. Please contact the medical monitor to discuss requests for less than 28 day washout period. * Known hypersensitivity to the components of the study therapy or its analogs. * Carcinomatous meningitis and/or symptomatic central nervous system (CNS) metastases. * Malignancies that are expected to alter life expectancy or may interfere with disease assessment. Patients with adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, or low-grade (Gleason score <= 6) localized prostate cancer, ductal carcinoma in situ (DCIS), and patients with prior history of malignancy who have been disease free for more than 3 years are eligible. * Serious cardiac illness or medical conditions such as unstable angina, pulmonary embolism, or uncontrolled hypertension. * Patients considered at risk for life-threatening QTc prolongation (i.e., personal or family history of Long QT syndrome, presence of implantable pacemaker or implantable cardioverter defibrillator, etc.). * Use of the following medications within 6 months prior to EC1456 administration: amiodarone, disopyramide, dofetilide, dronedarone, flecanamide, ibutilide, quinidine, or sotalol. * Need for concurrent anti-folate therapy such as methotrexate for rheumatoid arthritis. * Other concurrent chemotherapy, immunotherapy, radiotherapy, or investigational therapy. * Pregnant or lactating women. * Active uncontrolled infections. * Known active Hepatitis B or C infection. * Unable or unwilling to have a pretreatment scan performed with 99mTc-etarfolatide for any reason (such as claustrophobia, an inability to lie supine on an imaging table because of pain or cardiopulmonary disease, etc.).

Study Objectives The purpose of this study is to determine whether DCVAC/OvCa added to chemotherapy (carboplatin and gemcitabine as second line chemotherapy) may result in prolongation of progression free survival (PFS). Conditions: Ovarian Neoplasms, Ovarian Cancer (OvCa), Ovarian Epithelial Cancer Intervention / Treatment: BIOLOGICAL: DCVAC/OvCa in parallel with chemotherapy, DRUG: Standard of Care Location: Czechia, Poland, Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Females 18 years old and older * Patients with histologically confirmed, International Federation of Gynecology and Obstetrics (FIGO) stage III or IV epithelial ovarian, primary peritoneal or fallopian tube carcinoma (serous, endometrioid or mucinous), who had complete remission after first line platinum (Pt)-based chemotherapy and are selected to receive second line Standard of Care chemotherapy * Radiologically confirmed relapse after >6 months of remission (Platinum-sensitive patients), found up to 4 weeks prior study entry. * The patient must have at least one measureable target lesion as defined by the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria to be eligible for enrolment in the study Exclusion Criteria: * FIGO I,II epithelial ovarian cancer * FIGO III, IV clear cells epithelial ovarian cancer * Non-epithelial ovarian cancer * Borderline tumors (tumors of low malignant potential) * Prior or current systemic anti-cancer therapy for ovarian cancer [for example chemotherapy, monoclonal antibody therapy , tyrosine kinase inhibitor therapy, vascular endothelial growth factor (VEGF) therapy or hormonal therapy] except first line Platinum-based chemotherapy (with or without bevacizumab) * Previous radiotherapy to the abdomen and pelvis * Malignancy other than epithelial ovarian cancer, except those that have been in clinical remission (CR) for a minimum of 3 years, and except carcinoma in-situ of the cervix or non-melanoma skin carcinomas

Study Objectives RATIONALE: Drugs used in chemotherapy, such as bendamustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Stereotactic radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue. PURPOSE: This phase I trial is studying the side effects and best dose of bendamustine when given together with radiation therapy in treating patients with brain metastases caused by solid tumors. Conditions: Metastatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific Intervention / Treatment: DRUG: bendamustine, OTHER: laboratory biomarker analysis, PROCEDURE: Surgical Resection of Brain Metastases, RADIATION: Stereotactic body radiation therapy 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 to 4 brain metastases imaged by MRI/CT scans not involving thalamus, basal ganglia or brain stem. * No cancer originating in central nervous system * Candidate for clinically indicated surgery to resect brain lesions. * Karnofsky score of at least 60 * At least 18 years of age * Life expectancy of more than two months Exclusion Criteria: * Evidence of leptomeningeal metastases. * Need immediate treatment to prevent neurological deterioration. * Prior brain radiotherapy or surgery for current brain metastases. * Radiosensitive primary tumors such as small cell lung cancer, germ cell tumors, lymphoma, leukemia or multiple myeloma. * Absolute neutrophil count (ANC)<1500/mm3 or platelets <50,000/mms. * Brain metastasis diameter greater than 5 cm. * Not pregnant or nursing * More than 3 weeks since prior chemotherapy. * No evidence of ischemia on EKG and/or reduced cardiac ejection fraction (i.e., < 50%) on ECHO. * No known sensitivity or allergy to bendamustine hydrochloride or mannitol * No more than 3 prior cytotoxic chemotherapy regimens * No unresolved persistent toxicities for 4 weeks from prior chemotherapy or 6 weeks for nitrosoureas. * Calculated creatinine clearance <40 ml/min.

Study Objectives This phase II trial is studying sorafenib tosylate and gene expression in patients undergoing surgery for high-risk localized prostate cancer. Sorafenib tosylate 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. Studying samples of blood and tumor tissues in the laboratory from patients with prostate cancer may help doctors learn more about changes that occur in DNA after treatment with sorafenib tosylate Conditions: Adenocarcinoma of the Prostate, Stage II Prostate Cancer, Stage III Prostate Cancer Intervention / Treatment: DRUG: sorafenib tosylate, GENETIC: microarray analysis, OTHER: immunohistochemistry staining method, GENETIC: gene expression analysis, PROCEDURE: needle biopsy, PROCEDURE: therapeutic conventional surgery, OTHER: laboratory biomarker analysis, GENETIC: western blotting, GENETIC: RNA analysis Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: * Histologically confirmed adenocarcinoma of the prostate * Radical prostatectomy and lymph node dissection planned as primary therapy in a patient with acceptable surgical risk (e.g., cardiovascular, pulmonary, and functional status) * 10 year or longer life expectancy * Any of the following high-risk features: Clinical stage T2b (palpable bilateral involvement) OR surgically resectable T3 OR PSA >= 20 ng/ml OR overall Gleason grade >= 8 * No evidence of bone metastases on bone scan * No evidence of lymph nodes >= 2 cm in diameter on pelvic CT scan * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Hemoglobin >= 9.0 g/dl * Absolute neutrophil count (ANC) >= 1,500/mm^3 * Platelet count >= 100,000/mm^3 * Total bilirubin =< 1.5 x ULN * ALT =< 2.5 x the ULN * AST =< 2.5 x the ULN * INR =< 1.5 and aPTT within normal limits * Creatinine =< 1.5 x ULN or creatinine clearance > 60mL/min/1.73 m^2 * Men must agree to use adequate contraception (abstinence, hormonal in female partner, or barrier method of birth control) prior to study entry, for the duration of study participation, and for at least two weeks after stopping treatment * Signed informed patient consent Exclusion Criteria: * Prior therapy for prostate cancer including conventional androgen deprivation therapy, radiotherapy (external beam or brachytherapy), cryotherapy, and/or cytotoxic chemotherapy * Any known metastasis; patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis * Significant active medical illness which in the opinion of the investigator would preclude protocol treatment * Another malignancy, other than non-melanoma skin cancer, during the past 5 years * History of bleeding diathesis or unexpected surgical bleeding * Patients with active coagulopathy * Cardiac disease: 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 * Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy * Uncontrolled hypertension, as defined by systolic blood pressure consistently in excess of 150 mmHg, or diastolic pressure consistently in excess of 90 mmHg * Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months * Pulmonary hemorrhage/bleeding event >= CTCAE Grade 2 within 4 weeks of first dose of study drug * Any other hemorrhage/bleeding event >= CTCAE Grade 3 within 4 weeks of first dose of study drug * History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib * Patients may not be concurrently receiving any chemotherapy, immunotherapy, hormonal therapy, or molecular targeted agents to treat their prostate cancer * Patients may not be receiving any other investigational agents * Therapeutic anticoagulation with heparin, low-molecular weight heparin, or warfarin within the last 4 weeks * Patients may not be using rifampin, digoxin, quinidine, ketoconazole, itraconazole, cyclosporine, carbamazepine, phenytoin, phenobarbital, St. John's Wart, or products containing grapefruit juice * Patients may not be using bevacizumab or any other drugs that target VEGF or VEGF receptors * Active clinically significant infections (>= grade 2 NCI-CTCAE version 3.0); patients may enroll after infection resolves * HIV-positive patients receiving combination anti-retroviral therapy because of possible pharmacokinetic interactions with Sorafenib * Any condition that impairs patient's ability to swallow whole pills * Any malabsorption problem

Study Objectives This clinical investigation examined the influence of cytostatic chemotherapy with 5-fluorouracil, modulated by biologically active leucovorin, on patients' survival time following surgery for colon carcinoma Stage II. Conditions: Colon Cancer Stage II Intervention / Treatment: DRUG: Fluorouracil, DRUG: Leucovorin 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 histologically verified, operable colon carcinoma Stage II (RO, T3-4, N0, M0) * Age: less than 80 years * WHO Performance > 2 * Adequate bone marrow reserve, renal and hepatic functions * Informed consent Exclusion Criteria: * Rectal cancer * R1or R2 resection; carcinosis peritonei * Start of treatment > 42 days postop; other adjuvant radiotherapy, chemotherapy or immunotherapy * Serious concomitant disease, in particular chronically inflammatory large intestine, cardiopathic or metabolic disease, malignant second carcinoma

Study Objectives This phase I trial studies the side effects and best dose of ruxolitinib phosphate when given together with pembrolizumab in treating patients with stage IV triple negative breast cancer that has spread to other places in the body. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ruxolitinib phosphate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and ruxolitinib phosphate together may work better in treating patients with stage IV triple negative breast cancer. Conditions: Metastatic Malignant Neoplasm in the Bone, Stage IV Breast Cancer AJCC v6 and v7, Triple-Negative Breast Carcinoma Intervention / Treatment: OTHER: Laboratory Biomarker Analysis, BIOLOGICAL: Pembrolizumab, DRUG: Ruxolitinib Phosphate 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: * Age >= 18 years * Metastatic (stage IV) triple negative breast cancer that has progressed after at least one prior chemotherapy regimen in the metastatic setting or refusal of chemotherapy in the metastatic setting; non-measurable disease (i.e. bone metastases) is permitted * Histological confirmation of triple negative breast cancer defined as: * Her2/neu by fluorescence in situ hybridization (FISH) (ratio =< 1.8) or immunohistochemistry (IHC) (0 or 1+) * Estrogen receptor (ER) and progesterone receptor (PR) expression < 10% * Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 7 days prior to registration) * Platelet count >= 100,000/mm^3 (obtained =< 7 days prior to registration) * Total bilirubin =< 1.5 x upper limit normal (ULN) (obtained =< 7 days prior to registration) * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN or < 5 x ULN if organ involvement (obtained =< 7 days prior to registration) * Alkaline phosphatase < 5 x ULN (obtained =< 7 days prior to registration) * Serum creatinine =< 2 x ULN or 24 hour creatinine (Cr) clearance > 60 ml/min (obtained =< 7 days prior to registration) * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 * Ability to provide informed written consent and be able to adhere to the study visit schedule and other protocol requirements * Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study) * Willing to provide blood samples for correlative research purposes * Has existing archived tissue and is willing to consent to providing sample for correlative research purposes * Female subjects of childbearing potential should have a negative serum pregnancy =< 7 days prior to registration * Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year; Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject * Male subjects 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 * Radiographic or clinically measurable evidence of disease progression * Prior therapy with atezolizumab is acceptable providing that all atezolizumab-related toxicities have resolved Exclusion Criteria: * Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection, known positive for active infectious hepatitis, type A, B or C (past infection allowed), or psychiatric illness/social situations that would limit compliance with study requirements; Note: ongoing infection controlled on antibiotics/antifungal/antiviral medications are allowed * Any of the following prior therapies: * Cytotoxic chemotherapy =< 14 days prior to registration * Immunotherapy =< 14 days prior to registration * Biologic therapy (i.e. antibody therapies) =< 28 days prior to registration * Radiation therapy =< 14 days prior to registration * Targeted therapies (i.e. PARP inhibitors, =< 7 days or 5 half-lives whichever is shorter) * Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm =< 14 days prior to registration * Active uncontrolled central nervous system (CNS) metastases * Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive * Hypersensitivity to ruxolitinib or any of its excipients * Major surgery =< 28 days prior to registration; Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy * Clinically significant heart disease, including the following: * Active severe angina pectoris prior to registration * Acute myocardial infarction prior to registration * New York Heart Association classification IV cardiovascular disease or symptomatic class III disease * Note: patients with any of the above may be allowed after discussion amongst the investigators including the principal investigator * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to registration * Hypersensitivity to pembrolizumab or any of its excipients * Has had a prior anti-cancer monoclonal antibody (mAb) =< 4 weeks prior to registration or who has not recovered (i.e., =< grade 1 or at baseline level) from adverse events due to agents administered more than 4 weeks earlier * Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy who has not recovered (i.e., =< grade 1 or at baseline level) from adverse events due to a previously administered agent * Note: subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study * Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer * Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment * Has known history of, or any evidence of active, non-infectious pneumonitis * 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 * Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown: * Men or women of childbearing potential who are unwilling to employ adequate contraception * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment * Has received prior therapy with pembrolizumab, nivolumab, avelumab, durvalumab * Has received a live vaccine within 30 days of planned start of registration; Note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed * Evidence of pericardial involvement with metastatic breast cancer (effusion, pericardial thickening) * Radiographic evidence of pulmonary lymphangitic spread of metastatic breast cancer * Evidence of bilateral pleural involvement with metastatic breast cancer (effusions, pleural thickening) * Elevated serum lactate dehydrogenase level (LDH > laboratory ULN) associated with any clinical or radiographic evidence of intrathoracic metastatic breast cancer

Study Objectives This is a Phase II, open label, non-randomized study in patients with histologically or pathologically confirmed diagnosis of stage IIIB/IV, EGFR+ adenocarcinoma of the colon or rectum who have not received prior chemotherapy for their metastatic disease. Primary Study Endpoint: To assess the response rate, progression-free survival, and overall safety profile of a modified FOLFOX 6 plus cetuximab regimen in the first-line treatment of patients with metastatic colorectal cancer. Secondary Study Endpoint(s): To assess overall survival of patients with metastatic colorectal cancer who receive first-line therapy with a modified FOLFOX 6 + cetuximab regimen. Conditions: Colorectal Cancer Intervention / Treatment: DRUG: Cetuximab Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must have signed an IRB approved informed consent. * Patients with histologically or pathologically documented, stage IIIB or IV adenocarcinoma of the colon or rectum. * Patients with disease that is not amenable to potentially curative resection (i.e., inoperable metastatic disease). * Patients with tumors that are EGFR + by IHC staining. * Patients with ECOG Performance status of 0 or 1. * Patients, 18 years and older, must either be not of child bearing potential or have a negative serum pregnancy test within 7 days prior to registration. Patients are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or they are postmenopausal. * Bone marrow function: absolute neutrophil count (ANC) > or = 1,500/uL, equivalent to Common Terminology Criteria for Adverse Events (CTCAE, version 3) Grade 1. Platelets > or = 100,000/uL (CTCAE Grade 0 - 1). * Renal function: creatinine < or = 1.5 x institutional upper limit of normal (ULN), CTCAE Grade 1. * Hepatic function: bilirubin < or = 1.5 x ULN, CTCAE Grade 1. AST < or = 2.5 x ULN, CTCAE Grade 1. Exclusion Criteria: * Patients who received prior chemotherapy for metastatic disease. Prior adjuvant therapy with 5FU/LV and/or irinotecan is allowed provided it was completed at least 6 months prior to enrollment in this study. * Patents who received prior oxaliplatin. * Patients who received prior cetuximab or other therapy which specifically and directly targets the EGF pathway. * Patients with acute hepatitis. * Patients with active or uncontrolled infection. * Patients with a significant history of cardiac disease, i.e., uncontrolled hypertension, unstable angina, and congestive heart failure. * Prior allergic reaction to chimerized or murine monoclonal antibody therapy. * Any concurrent chemotherapy not indicated in the study protocol or any other investigational agent. * Patients with peripheral neuropathy > grade 1

Study Objectives The standard treatment choice for advanced hepatocellular carcinoma (HCC) is sorafenib, and its efficacy is limited. More active treatments were performed in patients with advanced HCC in China, which include radical hepatectomy or TACE. The study is to investigate whether the active treatment will profit survival of patients, and to evaluate the safety. Conditions: Hepatectomy, Hepatocellular Carcinoma, Sorafenib Intervention / Treatment: PROCEDURE: hepatic resection, PROCEDURE: transcatheter hepatic arterial chemoembolization, DRUG: sorafenib Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Male or female patients > 18 years of age. * Diagnosed to have advanced HCC (BCLC C stage). * Patients who have a life expectancy of at least 12 weeks. * Patients whose primary tumor can be resected. Definition of resectable in this study: * Tumor number <=2. * If number of tumors >= 3, then all tumors were located in the same lobe. * Without tumor invasion of the main trunk of the portal vein, or hepatic duct, or caval vein. * Hepatocellular carcinoma with histological diagnose or clinical diagnose according to AASLD. * No major post-operative complication. * Patients who have an ECOG PS of 0, or 1. * Cirrhotic status of Child-Pugh class A only. * The following laboratory parameters: Platelet count > 60 x 109/L Hemoglobin > 8.5 g/dL Albumin > 3.5 g/dL Total bilirubin < 25μmol/L Alanine transaminase (ALT) and AST < 2.5 x upper limit of normal Serum creatinine <1.5 x the upper limit of normal Prothrombin time (PT)<3 seconds above control. * Patients who give written informed consent. Exclusion Criteria: * Previous or concurrent cancer that is distinct in primary site or histology from HCC. * History of cardiac disease. * Active clinically serious infections (> grade 2 National Cancer Institute [NCI]-Common Terminology Criteria for Adverse Events [CTCAE] version 3.0) * Known history of human immunodeficiency virus (HIV) infection * Known Central Nervous System tumors including metastatic brain disease. * Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry. * History of organ allograft. * Known or suspected allergy to the investigational agent or any agent given in association with this trial. * Pregnant or breast-feeding patients. * Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study. * Excluded therapies and medications, previous and concomitant: Systemic chemotherapy and target drug other than sorafenib. Antiviral treatment is allowed. * Radiotherapy except for which done for bone metastases palliatively.

Study Objectives Phase I trial to study the effectiveness of combining bortezomib with paclitaxel in treating patients who have advanced or metastatic solid tumors. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining bortezomib with paclitaxel may kill more tumor cells. Conditions: Unspecified Adult Solid Tumor, Protocol Specific Intervention / Treatment: DRUG: bortezomib, DRUG: paclitaxel, 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 or cytologically confirmed locally advanced or metastatic solid tumor for which there is no curative treatment * No known brain metastases * Performance status - ECOG 0-2 * Performance status - Karnofsky 60-100% * WBC at least 3,000/mm^3 * Absolute neutrophil count at least 1,500/mm^3 * Platelet count at least 100,000/mm^3 * Bilirubin normal * AST/ALT no greater than 2.5 times upper limit of normal (ULN) * Creatinine no greater than ULN * Left ventricular function at least lower limit of normal if received prior doxorubicin * No grade II or IV tilt-table test * No symptomatic congestive heart failure * No unstable angina pectoris * No cardiac arrhythmia * No thrombotic event within the past 6 months * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No prior allergic reaction to compounds of similar chemical or biological composition to study drugs * No other concurrent uncontrolled illness * No ongoing or active infection * No psychiatric illness or social situation that would preclude study compliance * At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) * Prior paclitaxel allowed * At least 2 weeks since prior hormonal therapy * No concurrent steroids or hormonal therapy except steroids to prevent hypersensitivity reactions to paclitaxel or hormonal therapy for non-disease-related conditions (e.g., insulin for diabetes) * At least 4 weeks since prior radiotherapy * At least 4 weeks since prior surgery * Recovered from prior therapy * No other concurrent investigational agents * No concurrent combination anti-retroviral therapy for HIV-positive patients * No concurrent anticoagulation therapy * Concurrent pamidronate or zoledronate allowed for treatment of hypercalcemia or for palliation of skeletal metastases

Study Objectives The goal of this clinical research study is to learn if the combination of 2 drugs dabrafenib and trametinib can help to control melanoma that has or has not spread to the brain. The safety of this drug combination will also be studied. Dabrafenib is designed to block the mutated BRAF protein. This mutation is only found in moles of the skin and in melanoma cells. By blocking the protein, the drug may slow the growth of or kill cancer cells that have the protein. Trametinib is designed to block certain proteins that cause cancer cells to grow and multiply. This may cause the cancer cells to die. Conditions: Melanoma Intervention / Treatment: DRUG: GSK2118436, DRUG: GSK1120212 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: * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Patients must have histologically or cytologically confirmed Stage IV or recurrent or unresectable Stage III melanoma. * BRAF mutation-positive melanoma (i.e., V600E, V600K or V600D) * For Cohort A, patients must have easily accessible tumor for a mandatory biopsy. This is not required for patients enrolled on Cohort B. * Patients must have measurable disease, defined by RECIST 1.1 * Patients must have tumor lesions which is refractory or resistant to a selective BRAF inhibitor (RO5185426 or GSK2118436). * Age >= 16 years. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Patients must have organ and marrow function as defined below: · absolute neutrophil count >= 1,500/mcL · platelets >= 75,000/mcL · total bilirubin <= 1.5 × institutional upper limit of normal: no restriction to serum bilirubin level if Gilbert's syndrome is diagnosed or suspected · AST(SGOT)/ALT(SGPT) <= 2.5 × institutional upper limit of normal, (<= 3x upper limit of normal for AST and ALT for those subjects with liver metastasis) · creatinine <= 1.3 × institutional upper limit of normal OR · creatinine clearance >= 60 mL/min/1.73 m2 for patients with creatinine levels above 1.3 X institutional upper limit of normal. * Ability to understand and the willingness to sign a written informed consent document. * For Cohort B, patients must have at least 1 measureable parenchymal brain metastasis of at least 10 mm in the greatest diameter and no greater than 40 mm diameter. There must be at least one parenchymal brain metastasis that has not received any previous locally-directed treatment (i.e. surgery or radiation), or that has progressed after prior treatment for the brain metastases (i.e. surgery or radiation). * Male subjects must agree to use contraception, this criterion must be followed from the time of the first dose of study medication until 4 weeks after the last dose of study medication. However, it is advised that contraception be used for a total of 16 weeks following the last dose (based on the lifecycle of sperm). * A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/mL and estradiol < 40 pg/mL (<140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use contraception if they wish to continue their HRT during the study. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method. * (cont' from Inclusion #12) * Child-bearing potential and agrees to use one of the contraception methods listed in Section 7.1.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 4 weeks after the last dose of study medication, and must have a negative serum pregnancy test within 14 days prior to the start of dosing. Note: Oral contraceptives are not reliable due to potential drug-drug interaction. Exclusion Criteria: * Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) except a selective RAF inhibitor. * Patients must not have previously received a selective BRAF inhibitor (RO5185426, GSK2118436) and a selective MEK inhibitor (AZD6244, GSK1120212) concurrently. * Received an investigational anti-cancer drug within four weeks or five half-lives (whichever is shorter) of study drug administration, other than BRAF inhibitor--at least 14 days must have passed between the last dose of the prior investigational anti-cancer drug and the first dose of study drug. However, there is no required washout period for any BRAF inhibitors at least until the baseline biopsy is performed. * Current use of a prohibited medication or requires any of these medications during treatment with study drug. * Any major surgery, within the last 3 weeks. Radiotherapy, or immunotherapy within the last 2 weeks. * Unresolved toxicity greater than NCI-Common Toxicity Criteria for Adverse Effects (CTCAE) v4 Grade 1 from previous anti-cancer therapy except alopecia and peripheral neuropathy, for which <= grade 2 toxicity is allowed to participate. * Presence of rheumatoid arthritis. * History of retinal vein occlusion or central serous retinopathy, or predisposing factors to retinal vein occlusion or central serous retinopathy (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes). * Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs. * Brain Metastases a. For cohort A, patients will be excluded if they have brain metastases, unless they have been previously treated brain metastases with surgery or stereotactic radiosurgery and the disease has been confirmed stable (i.e., no increase in lesion size) for at least 4 weeks with MRI scans using contrast prior to Day 1. Subjects are not permitted to receive enzyme-inducing anti-epileptic drugs and/or steroids to control symptoms/signs of brain metastases. Patients previously treated with whole brain radiation therapy must have confirmed stable disease for at least 12 weeks prior to starting treatment. However, untreated asymptomatic brain metastasis less than 10 mm will be allowed if no steroid and anti-epileptic drugs are used. * 10 (con't) b. For cohort B, patients may not have any evidence of leptomeningeal disease. Use of corticosteroids is permitted as long as the dose of steroids required for symptom control has been stable or decreasing for at least 3 weeks prior to the first dose of study treatment. * History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within the past 6 months. * Corrected QT interval (QTc) >= 480 msec (>= 500 msec for subjects with Bundle Branch Block). * Uncontrolled arrhythmias. * Subjects with controlled atrial fibrillation for >1 month prior to study Day 1 are eligible. * Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system. * Abnormal cardiac valve morphology (subjects with minimal abnormalities can be entered on study if deemed not clinically significant) * Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drugs, or excipients. NOTE: To date there are no known FDA approved drugs chemically related to GSK2118436 or GSK1120212. * Pregnant or lactating female. * Unwillingness or inability to follow the procedures required in the protocol. * Uncontrolled diabetes, hypertension or other medical conditions that may interfere with assessment of toxicity * Subjects with known glucose 6 phosphate dehydrogenase (G6PD) deficiency.

Study Objectives An open-label study available to all eligible participants from Study B1371019 and participants originating from Study B1371012 continuing on study intervention with azacitidine with or without glasdegib. Conditions: Acute Myeloid Leukemia, Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia Intervention / Treatment: DRUG: Glasdegib, DRUG: Azacitidine Location: Hungary, Mexico, Canada, Japan, Italy, Spain, United Kingdom, Austria, Czechia, France, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Any participant who continues to demonstrate clinical benefit (as determined by the Principal Investigator) from study treatment with azacitidine with or without glasdegib in this Study or from Study B1371012. * Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol. Exclusion Criteria: * Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. * Female participants who are pregnant or breastfeeding (if continuing to receive study intervention); * Participant has been withdrawn from Study B1371019 and Study B1371012 for any reason (including INT cohort participants required to end study treatment)

Study Objectives People with pancreatic cancer usually have a large amount of the cancer in the area of the pancreas and around it when they are diagnosed with it. Or their cancer has spread (metastasized)outside that area of the abdomen and is not able to be surgically removed (resected). For patients with metastatic disease, one standard treatment is the combination of gemcitabine and erlotinib. This combination has shown slightly longer survival compared to getting gemcitabine alone. For patients with localized but unresectable disease, the standard treatment remains controversial. Early studies showed that chemotherapy and radiation together was better than either one used alone. The greatest benefit of external beam radiotherapy may be after a period of full-dose chemotherapy alone, to help the rapid spread. A problem of beginning treatment with standard radiotherapy is that the doses of chemotherapy usually have to be reduced sometimes by half. Studies have already shown that low dose radiotherapy (LDRT)is safe. This study will evaluate the safety of LDRT instead of standard doses with full dosing of gemcitabine and erlotinib in patients with locally advanced or limited metastatic pancreatic cancer. Patients will be enrolled in groups of 3 to 6 each with a slightly higher dose of LDRT and erlotinib. For patients with locally advanced disease, this protocol also may help because most patients develop and die from spread to the liver and abdominal cavity. Conditions: Pancreatic Carcinoma Non-resectable, Metastatic Pancreatic Cancer Intervention / Treatment: DRUG: gemcitabine, DRUG: Erlotinib, RADIATION: low dose fractionated radiotherapy Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must have a diagnosis of adenocarcinoma of the pancreas that is not amenable to curative surgical resection. Patients with locally advanced unresectable disease and those patients with metastatic disease that can be encompassed in the radiation fields for this study (as assessed by treating radiation oncologist) are eligible. * Patients may not have received any prior chemotherapy for locally advanced or metastatic pancreatic cancer. Prior adjuvant chemotherapy completed >1 year previously is allowed. * Patients must be able to provide informed consent and HIPAA consent. * Patients must be >=18 years of age * Adequate hematologic and organ function: * ANC >= 1,000/μL, platelets >= 100,000/μL, hemoglobin >= 9.0/dL * Bilirubin: <=1.5X ULN * ALT/AST < 3.0 X upper limit of normal * Serum Creatinine: WNL * Albumin > 2.5 g/dL * Measurable and non-measurable disease are permitted * ECOG performance status 0-1 * Patients must be able to swallow oral medications * Patients must be able to comply with study and follow up procedures Exclusion Criteria: * No prior radiation therapy to the abdomen. * Patients must not have any other active illness (e.g. active/uncontrolled infection, uncontrolled cardiac disease, etc.) that would preclude safe therapy in the judgment of the treating physicians. Patients may be enrolled while still on antibiotics as long as clinical signs of active infection are absent. * Patients with concurrent active malignancy requiring therapy are not eligible. Patients with a history of malignancy within any timeframe not requiring ongoing therapy are eligible.

Study Objectives The purpose of this study to find out whether mirdametinib is a safe treatment for people with advanced solid tumor cancer that has certain mutations. Researchers will look at whether mirdametinib on its own or in combination with the drug fulvestrant is a safe treatment that causes few or mild side effects in people with advanced solid tumor cancer. Conditions: Breast Cancer, Breast Cancer Stage IV, HER2-negative Breast Cancer, Solid Carcinoma, MEK1 Gene Mutation, MEK2 Gene Mutation, Metastatic Breast Cancer Intervention / Treatment: DRUG: Mirdametinib, DRUG: Fulvestrant 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: Subjects are eligible to start the treatment in the study only if all of the following criteria apply: Arm 1 (metastatic breast cancer): * Female adults (>=18 years of age on the date of informed consent) * Postmenopausal or receiving ovarian suppression (including GnRH agonists such as goserelin) * Histologically confirmed hormone receptor-positive metastatic breast cancer with evidence of progression on at least 1 prior line of therapy for metastatic disease which should have included a CDK4/6 inhibitor in combination with endocrine therapy. Prior chemotherapy is permitted. * ER+ as defined by immunohistochemistry (IHC) >=1% by local laboratory testing (as per the ASCO-CAP guidelines) * HER2-negative, as defined by the negative in situ hybridization test (FISH, CISH, or SISH) or an IHC status of 0, 1+ or 2+ by local laboratory testing. If IHC is 2+ (i.e. indeterminate), then a negative in situ hybridization test (FISH, CISH, or SISH) is required (as per the ASCO-CAP guidelines). * NF1 loss of function or another MAPK-activating genomic alteration documented by a CLIA-certified NGS assay at any time before the start of treatment. Note: archival tissue, if available and collected within 6 months of enrollment, may be used for this testing in lieu of fresh tissue. Arm 2 (advanced solid cancers): * Male or female adults (>=18 years of age on the date of informed consent) * Histologically confirmed advanced, metastatic solid tumor cancer for which there is no available therapy known to confer clinical benefit. Colorectal, anal, small bowel, biliary or ampullary cancers are not eligible. * Class 1 or class 2 MEK1 or MEK2 mutations, as described below, documented by a CLIA-certified NGS assay at any time before the start of treatment. Class 3 MEK1 or MEK2 mutations as described in that paper are excluded. A complete list of the mutations allowed based on that paper can be found below, however, rare mutations not listed in this table may be permitted at the discretion of the principal investigator of the study. Note: archival tissue, if available and collected within 6 months of enrollment, may be used for this testing in lieu of fresh tissue. Class 1 - Permitted: MEK1 D67N, MEK1 P124L, MEK1 P124S Class 2 - Permitted: MEK1 K57N, MEK1 C121S, MEK1 F53L, MEK1 Q56P Class 3 - Excluded: MEK1 L98-I103, MEK1 I99-K104, MEK1 E102-I103 The permitted mutations shown above are for MEK1. MEK1 and MEK2 are closely related, are structurally similar, share 79% amino acid identity, and they share equal ability to phosphylate their ERK substrates30. While the experiments performed above classify individual MEK1 mutations only, the class 3 mutations in MEK1 all share in-frame deletions that remove a potent negative regulatory element of MEK1. These are easily distinguishable from other mutations in MEK1. Therefore, the identification of exclusionary class 3 MEK2 alterations will be straightforward as well, with paralogous mutant residues in MEK1 and MEK2 defined in the manuscript above. A table showing the permitted enrolling paralogous class 1 and class 2 residues are shown in the table below, again with the caveat that rare mutations in MEK2 not listed in the table below may be eligible at the discretion of the principal investigator. MEK1: F53, Q56, K57, V60, D67, C121, P124, Y130, E203 MEK2: F57, Q60, K61, V64, D71, C125, P128, Y134, E207 All Arms: * Patient (or Legally Authorized Representative [LAR]) must sign written informed consent form before any study-specific procedure is performed * ECOG performance score of 0 or 1 * Life expectancy of >=3 months * At least one tumor lesion measurable by RECIST 1.1. A lesion in a previously irradiated area may be considered as measurable disease if there is objective evidence of progression of the lesion by RECIST 1.1 (Eisenhauer EA et al, 2009) between the prior radiotherapy and the screening CT or MRI scan. * Adequate bone marrow function at screening, as determined by: * Absolute neutrophil count (ANC) >1,500/mm3 (CTCAE Grade <=1) * Platelet count >100,000 mm³ * Hemoglobin >9.0 mg/dL * Adequate kidney function at screening, as determined by ° Estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 calculated by the CKD-EPI equation (CTCAE Grade <= 1). * Adequate hepatic function at screening, as determined by: ° Total bilirubin <=1.5 x ULN if baseline was normal or <=1.5 x baseline if baseline was abnormal (CTCAE Grade <=1). Patients with previously documented Gilbert's Syndrome may have total bilirubin <=3 x ULN. * AST <=3.0 x ULN if baseline was normal or <=3.0 x baseline if baseline was abnormal (CTCAE Grade <=1). * ALT <=3.0 x ULN if baseline was normal or <=3.0 x baseline if baseline was abnormal (CTCAE Grade <=1). * Adequate coagulation function at screening, as determined by: ° INR <=1.5 x ULN if not on anticoagulant therapy or >1.5 x baseline if on anticoagulant therapy (CTCAE Grade <=1). If the patient receives anticoagulant therapy, the dose must be stable for at least 2 weeks before the start of treatment. ° PTT <=1.5 x ULN * Adequate cardiac function at screening, as determined by: * Systolic blood pressure <150 mmHg and diastolic blood pressure <90 mmHg (CTCAE Grade <=1). Note: Anti-hypertensive medications are permitted, and if a patient does not meet these eligibility criteria at time of screening, treatment with additional anti-hypertensive agents is permissible at the discretion of the investigator, and blood pressure can be rechecked at a subsequent visit. Measured blood pressures that fall out of this range after screening do not render patients ineligible, however every effort should be made to medically manage these elevated blood pressures at the investigator's discretion. * LVEF >=50% by MUGA or ECHO. * No clinically significant ECG waveform abnormalities at the investigator's discretion * QTcF <=470 ms * Adequate serum lipid profile at screening, as determined by ° Serum cholesterol <300 mg/dL ° Serum triglycerides <300 mg/dL * Adequate glycemic control at screening, as determined by ° Fasting blood glucose <140 mg/dL or ° Random blood glucose <250 mg/dL Note: Anti-hyperglycemic medications are permitted if a patient does not meet these eligibility criteria at time of screening. Blood glucose measurements that fall out of this range do not render patients ineligible, and appropriate glycemic control at subsequent visits is at the discretion of the investigator. * Blood calcium and phosphate levels within normal levels per institutional lab standard at screening (calcium level may be corrected for albumin at the investigator's discretion) * Adequate ophthalmological exam in both eyes at screening, as determined by ° Intraocular pressure <=21 mmHg ° No clinically significant abnormalities on the ocular tomography (OCT), including no evidence of ocular abnormality that would be considered a significant risk factor for central serous retinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration (mild and controlled / stable age-related macular degeneration may be acceptable at the investigator's discretion). * Able and willing to comply with all aspects of the protocol Contraception and Pregnancy Testing Arm 1 (ER-positive metastatic breast cancer): * Not applicable (subjects must be female and postmenopausal or receiving ovarian suppression) Arm 2 (advanced solid cancers with MEK1 or MEK2 mutations): * Male subjects must agree to the following during the treatment period and for at least 6 months after the last dose of study treatment: ° Refrain from donating sperm AND either: ° Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR * Must agree to use a male condom when having sexual intercourse with a woman of childbearing potential (WOCBP). - Women of childbearing potential (WOCBP) must * Have a negative pregnancy test at screening and within 72 hours before the start of treatment AND ° Must agree to use a contraceptive method that is highly effective during the treatment period and for at least 6 months after the last dose of study treatment. Suitable methods of contraception are described in Section 11.5 AND ° Must agree not to donate eggs (ova, oocytes) for the purpose of reproduction during the study and for a period of 6 months after last dose of study treatment. Exclusion Criteria: Subjects are excluded from the study if any of the following criteria apply: Medical and surgical history * History of HIV with the following exceptions: ° Patients with CD4+ T-cell (CD4+) counts >= 350 cells/uL * History of AIDS-defining opportunistic infection with the following exceptions: * Patients without opportunistic infection within the past 12 months * Patients on prophylactic antimicrobials unless the specific antimicrobial drug(s) has an interaction or overlapping toxicity with the proposed treatment as determined by the investigator * History of active Hepatitis B or Hepatitis C infection at screening with the following exceptions: * Patients with Hepatitis B on a suppressive antiviral therapy * Patients with Hepatitis C who have completed curative antiviral treatment and have an undetectable viral load * History (within 5 years) or current evidence of neoplastic disease other than the cancer under study, except cervical carcinoma in situ, superficial noninvasive bladder tumors, curatively treated Stage I-II non-melanoma skin cancer, or any other previous cancer curatively treated <5 years before the start of treatment. * Current evidence of untreated/unstable symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or spinal cord compression. Exception: Patients are eligible if neurological symptoms are stable for 14 days prior to the first treatment dose and no CNS surgery or radiation has been performed for 28 days, or 14 days of SRS. * Current evidence of CTCAE Grade >1 toxicity before the start of treatment, except for hair loss. ° Subjects with Grade 2 neuropathy may be eligible at the investigator's discretion. * History or current evidence of ocular abnormalities on ophthalmologic examination that would be considered a risk factor for central serous retinopathy, RVO or neovascular macular degeneration (mild and controlled age-related macular degeneration may be acceptable at the investigator's discretion) * Current evidence of incomplete recovery from surgery or radiotherapy at screening or planned major surgery or radiotherapy during the treatment. Minor elective surgery may be acceptable at the investigator's discretion. * History or current evidence of significant (CTCAE Grade >=2) infection or wound within 2 weeks before the start of treatment. * History or current evidence of significant cardiovascular disease within 6 months before the start of treatment. This includes, but may not be limited to: unstable angina, new-onset angina, myocardial infarction, arterial thrombosis, pulmonary embolism, CVI/TIA/stroke, pericarditis (any CTCAE grade), pericardial effusion (CTCAE Grade >=2), non-malignant pleural effusion (CTCAE Grade >=2), malignant pleural effusion (CTCAE Grade >=3), congestive heart failure (NYHA Class II - IV) or cardiac arrhythmia requiring anti-arrhythmic therapy, except the following * Subjects receiving digoxin, calcium channel blockers, or beta-adrenergic blockers may be eligible at the investigator's discretion if the dose has been stable for >=2 weeks before the start of treatment. * Subjects with sinus arrhythmia and infrequent premature ventricular contractions may be eligible at the investigator's discretion. * History or current evidence of malabsorption syndrome, major surgical GI resection or other GI conditions that may impair absorption of mirdametinib * Known or suspected hypersensitivity or allergy to any of the study drugs or excipients contained in the study drug formulations. In addition, allergy to other medications or other type of hypersensitivity may warrant exclusion at the investigator's discretion. * Female subjects who are pregnant or breastfeeding. * History or current evidence of any other medical or psychiatric condition or addictive disorder, or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with study participation, or require treatments that may interfere with the conduct of the study or the interpretation of study results. Prior or concomitant treatments * Prior therapy with mirdametinib or any other MEK1/2 inhibitor (e.g., selumetinib, trametinib, cobimetinib, binimetinib) at any time before the start of treatment * Prior systemic any anti-cancer therapy within five half-lives or two weeks (whichever is shorter), excluding hormonal therapy for metastatic breast cancer, before the start of treatment. * Prior radiotherapy to the orbital region at any time before the start of treatment * Prior radiotherapy to tumor lesion(s) that will be chosen as target lesions within 4 weeks before the start of treatment, unless the lesion(s) exhibited objective progression between the prior radiotherapy and the screening CT or MRI scan. ° Prior palliative radiotherapy to non-target lesions may be allowed at the investigator's discretion at any time before the start of treatment. * Prior therapy with a live vaccine(s) within 4 weeks before the start of treatment or likely to require live vaccine(s) at any time during the treatment. * Injectable flu vaccine (inactivated or recombinant) may be permitted at the investigator's discretion at any time before or during the treatment. * Covid-19 vaccination (any type) is permitted either before or during this protocol and does not preclude trial enrollment, at the discretion of the investigator. * Prior antibiotic therapy for active infection <=2 weeks before the start of treatment * Prior therapy with platelet or blood transfusion for the treatment of thrombocytopenia within 2 weeks before the start of treatment. * Blood transfusion for the treatment of anemia within 2 weeks before the start of treatment may be acceptable at the investigator's discretion. * EPO for the treatment of anemia within 2 weeks before the start of treatment may be acceptable at the investigator's discretion * Prior therapy with G-CSF or GM-CSF for the treatment of leukopenia within 2 weeks before the start of treatment * Prior therapy with systemic or topical ophthalmic glucocorticosteroids within 2 weeks before the start of treatment (except for subjects who receive glucocorticosteroid replacement therapy at physiologic doses and / or inhaled or non-ophthalmic topical corticosteroids)

Study Objectives The investigators hypothesis is that free fatty acids (FFA) accumulation in non fatty tissues would lead to insulin resistance and hyperandrogenism in PCOS women. Accordingly, Peroxisome Proliferator-Activated Receptor gamma (PPARγ) agonist (rosiglitazone) would be a great therapeutic option for PCOS as their activation induces transcription factors of gene implicated in fatty acids metabolism. The aim is to verify if insulin-related hyperandrogenism can be reversed in women having polycystic ovary syndrome following an 8-week treatment with rosiglitazone compared to simple insulin reduction with acarbose. For the purpose of this study, 14 lean women (BMI ≤ 25 kg/m2) and 36 obese women (BMI 30-39 kg/m2) with PCOS as well as 14 lean and 14 obese control women will be recruited to determine their insulin sensibility (insulin levels, M-value, metabolic clearance rate of glucose)and FFA metabolism (FFA levels, rythm of apparition and disapearance of FFA) during a 75g oral glucose tolerance test and a 2-step insulin-glucose clamp. Conditions: Polycystic Ovary Syndrome Intervention / Treatment: DRUG: Rosiglitazone, DRUG: Acarbose Location: Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: BASIC_SCIENCE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: PCOS : * Biochemical hyperandrogenism (free testosterone >= 50 pmol/l) * Oligomenorhea (<= 8 menstrual cycle per year) Health volunteers : * Normal menstrual cycle * Normal levels of free and total testosterone * No family history with PCOS Exclusion Criteria: * Diabetes or glucose intolerance * Current or past use within 3 months of oral contraceptives * Current or past use within 3 months of medications known to affect insulin sensitivity (metformin, PPARy agonists, b-blockers, thiazides, calcium channel blockers, glucocorticoids, etc.) * Pulmonary, cardiac, renal, hepatic, neurologic, psychiatric, infectious or neoplastic disease (other than non-melanoma skin cancer) * Documented or suspected recent (within one year) history of drug abuse or alcoholism * Use of any investigational drug within three months prior to study onset Healthy volunteers : * History of gestational diabetes * Positive family history for first-degree relative with diabetes * Disorders linked to insulin resistance (hypertension, dyslipidemia or acanthosis nigricans)

Study Objectives The purpose of the present study is to quantify the degree of modulation, if any, in the perioperative inflammatory response associated with statins use. Specifically, we hypothesize that: In a population of patients undergoing elective orthopedic spine surgery, administration of a specific statin (Simvastatin, Zocor®, Merck Pharmaceuticals), will be associated with a decrease in perioperative inflammatory markers when compared to patients not taking statins Conditions: Perioperative Inflammatory Response Intervention / Treatment: DRUG: Simvastatin, DRUG: Placebo Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * Patients scheduled for elective major spine surgery (multilevel (2-6 level) open thoracic or lumbar spine surgery with instrumentation) Exclusion Criteria: * Pregnancy * Lactating females * Oral or parenteral corticosteroid use in the past 30 days * Elevation of AST or ALT > 3x normal * Elevation of creatinine kinase > 2x normal * Previous adverse drug reaction to any medication in the statin class * Current use of fibrates, niacin, itraconazole, ketoconazole, macrolide antibiotics, HIV protease inhibitors and/or nefazodone * Active liver disease * Current statin use * Anti-inflammatory use of the following medications within the last 30 days: * Sulfasalazine * Mycophenolate * Cyclosporine * Cyclophosphamide * Azathioprine * Chlorambucil * Minocycline * Myochrysine * Penicillamine * Hydroxychloroquine * Leflunomide * Any medications listed in 3 or 10 above in the post-operative period * Use of Activated protein C at any time during the patients hospitalization * Use of anti-inflammatory medications listed below within the last 30 days: * Leflunomide * Sulfasalazine * Mycophenolate * Cyclosporine * Cyclophosphamide * Azathioprine * Chlorambucil * Minocycline * Myochrysine * Penicillamine * Hydroxychloroquine * Methotrexate

Study Objectives Primary Objective: 1. To determine the objective response rate (complete plus partial) to the combination of capecitabine (Xeloda) and oxaliplatin (Eloxatin) (XELOX) in patients with adenocarcinoma of the small bowel and ampulla of Vater. Secondary objectives include determining the toxicity, time-to-treatment failure, and overall survival rates in patients treated with this combination. Conditions: Gastrointestinal Cancer Intervention / Treatment: DRUG: Capecitabine, DRUG: Oxaliplatin Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must have histologically or cytologically confirmed adenocarcinoma of the small bowel or ampulla of Vater that is either unresectable or metastatic. * Patients must have measurable disease as per the modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria. * Patients may be previously untreated or have received previous systemic therapy, limited to 5-FU/leucovorin or capecitabine, as adjuvant or neoadjuvant therapy or as a radiosensitizer. Patients may have received capecitabine or 5-FU administered as a radiosensitizing agent concurrently with external beam radiotherapy as preoperative or postoperative therapy. Patients may have received capecitabine or 5-FU/leucovorin as part of adjuvant chemotherapy. * If radiation was previously received, the measurable disease must be outside the previous radiation field. * A minimum of 4 weeks must have elapsed since completion of any prior chemotherapy or radiotherapy. A minimum of 4 weeks must have elapsed since any prior surgery. * Eastern Cooperative Oncology Group (ECOG) Performance Status of less than or equal to 2. * Adequate bone marrow function defined as absolute peripheral granulocyte count of greater than or equal to 1500 mm3, platelet count greater than or equal to 1500 mm3, and hemoglobin greater than or equal to 10 gm/dL. * Adequate renal function, defined as serum creatinine less than or equal to 1.5 * ULN and calculated creatinine clearance >30 mL/min. * Patients must have adequate hepatic function: total bilirubin less than or equal to 1.5 gm/dL; serum albumin greater than or equal to 2.5 gm/dL. If the patient does not have liver metastasis, transaminases may be up to 2 * the ULN. If the patient has liver metastasis, transaminases up to 5 * Upper Limit of Normal (ULN) are allowed. * Negative urine or serum pregnancy test in women with childbearing potential, within one week prior to initiation of treatment. * The effects of the combination of oxaliplatin and capecitabine on the developing fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant while participating in this study, she should inform her treating physician immediately. * Patients must sign an Informed Consent and Authorization indicating that they are aware of the investigational nature of this study and the known risks involved. * Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of XELOX in patients <18 years of age, children are excluded from this study. * Patients taking therapeutic doses of coumarin-derivative anticoagulants should be switched to low-molecular-weight heparin (LMWH). Low-dose Coumadin (e.g. 1 mg by mouth (PO) per day) in patients with in-dwelling venous access devices is allowed. Exclusion Criteria: * Patients with prior exposure to platinum therapy are excluded. Patients who have received prior chemotherapy for metastatic disease are excluded. * Patients who have had chemotherapy within 4 weeks (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 may not be receiving any other investigational agents nor have received any investigational drug 30 days prior to enrollment. * Patients with known brain metastases are excluded from this clinical trial because of their poor prognosis and their risk for progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. * Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation. Prior surgical therapy affecting absorption. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with XELOX. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated. * Patients with extensive symptomatic fibrosis of the lungs. * Peripheral neuropathy > grade 1. * Known Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) * Patients receiving therapeutic doses of coumarin-derivative anticoagulant therapy are excluded since a drug interaction between capecitabine and coumarin anticoagulants has been reported. Patients requiring anticoagulation who may be safely switched to LMWH are eligible.