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Study Objectives Primary objectives To determine maxi tolerated dose of Temodar® in combo w O6-benzylguanine administered for 5 consecutive days in pts w progressive/recurrent GBM To characterize toxicity associated w Temodar® in combo w O6-BG administered for 5 consecutive days in pts w progressive/recurrent GBM To determine Neulasta®-supported MTD defined as the MTD of Temodar® in combo with O6-BG administered for 5 days while receiving Neulasta® once per treatment cycle between days 7 \& 14 in pts w progressive/recurrent GBM To obtain preliminary response rates of Temodar® in combo w O6-BG administered for 5 consecutive days in pts w progressive/recurrent GBM Conditions: Glioblastoma, Gliosarcoma Intervention / Treatment: DRUG: Temodar and O6-Benzylguanine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Pts have histologically proven supratentorial GBM * Pts have recurrent/progressive MG. If pt received stereotactic radiosurgery / brachytherapy as part of their prior therapy, then histologic confirmation of recurrence/metabolic imaging consistent w recurrent tumor is recommended but not mandated * There must be measurable disease on contrast-enhanced magnetic resonance imaging study / CT scan performed <2wks of study drug administration * Interval of >12 wks between completion of XRT & enrollment on protocol * Interval of >4 wks between prior chemo & enrollment on protocol unless there is unequivocal evidence of tumor progression * Interval of >2 wks between prior surgical resection & enrollment on protocol unless there is unequivocal evidence of tumor progression * Age >18 yrs * KPS >70 percent * Following baseline study will be required <1wk of study drug administration: serum creatinine < 1.5 x ULN & Hematologic Status * Following baseline studies will be required <1wk of study drug administration: absolute neutrophil count >2000 cells/microliter; platelet count >125,000 cells/microliter * Following baseline studies will be required <1 wk of study drug administration: serum SGOT & total bilirubin < 2.5 x ULN * Signed informed consent, approved by IRB, will be obtained prior to initiating treatment * Pts w Reproductive Potential: Pts must agree to practice effective birth control measures while on study & for 2 months after completing therapy Exclusion Criteria: * Pregnant/breast feeding women/ women/men w reproductive potential not practicing adequate contraception. Therapy may be associated w potential toxicity to fetus/child that exceeds mini risks necessary to meet health needs of mother * Prior treatment w O6-BG + Temozolomide in combo * Active infection requiring intravenous antibiotics * Known diagnosis of HIV infection * Pts w history of another primary malignancy that is currently clinically significant/currently requires active intervention * Pts unwilling/unable to comply w protocol due to serious medical/psychiatric condition * Pts who have received investigational drugs <2 wks prior to start on study drug/have not recovered from side effects of such therapy.

Study Objectives Safety study of ABT-263 in Combination with Paclitaxel in Subjects with Solid Tumors. Conditions: Solid Tumors Intervention / Treatment: DRUG: ABT-263, DRUG: paclitaxel Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria * Subject must be greater than or equal to 18 years of age. * Subject must have a histologically and/or cytologically documented cancer for which paclitaxel has been determined an appropriate therapy, per the Investigator. * Subjects with brain metastases must have clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by 21 days of stable neurologic function and no evidence of CNS disease progression as determined by CT or MRI within 28 days prior to the first dose of study drug. * Subject has an Eastern Cooperative Oncology Group (ECOG) score of less than or equal to 1. * Subject must have adequate bone marrow, renal and hepatic function per protocol defined local laboratory testing parameters. Exclusion Criteria * The subject has an underlying, predisposing condition of bleeding or currently exhibits signs of bleeding. The subject has a recent history of thrombocytopenia associated with bleeding within 1 year prior to first dose of study drug. * Subject is currently receiving or requires anticoagulation therapy (e.g., warfarin at any dose) or any drugs or herbal supplements that affect platelet function, with the exception of low-dose anticoagulation medications such as heparin that are used to maintain the patency of a central intravenous catheter. * The subject has active peptic ulcer disease or other potentially hemorrhagic esophagitis/gastritis. * The subject has active immune thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA), or a history of being refractory to platelet transfusions (within 1 year prior to the first dose of study drug). * The subject has a significant history of cardiovascular (e.g., MI, thrombotic or thromboembolic event in the last 6 months), renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease that in the opinion of the investigator would adversely affect his/her participating in this study.

Study Objectives Chronic lymphocytic leukemia (CLL) is increasingly believed to be closely related to chronic stimulation of healthy B-cells. Identification of antigen(s) are relevant for the stimulation of CLL precursor cells is therefore of high interest. The investigators found recently evidence that a herpes virus is involved in this process of stimulation. Consequently, elimination of the antigenic stimulation of leukemic cells by this herpes virus may be expected to reduce or even inhibit propagation of leukemic cells. The investigators hypothesize that inhibition of CMV replication by a short course of antiviral treatment may reduce significantly proliferation rates of leukemic cells. To test this hypothesis, the investigators will treat 20 CLL patients with an antiviral drug for 3 months in a proof-of-concept clinical trial and leukemic cell counts measured before and after antiviral treatment. Antiviral treatment has the potential to treat the disease at its origin and therefore more efficiently than conventional chemotherapeutic regimens. Conditions: Chronic Lymphocytic Leukemia Intervention / Treatment: DRUG: Valganciclovir Location: Austria Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * CLL confirmed by immunophenotyping and a relative preponderance of leukemic cells of >70% * ANC >1.500 /µl, Thrombocyte count >100.000 /µl und hemoglobin value >11 g/dl * CLL patients with expression of immunoglobulin heavy chains (IGHV) 1-69 or 3-21 * Seropositive for CMV-specific IgG-antibodies * >= 18 years years of age * Written informed consent * Able to comply with the protocol * If female, should not be pregnant or be breast-feeding. Women of child-bearing age must have a negative serum pregnancy test within 28days prior to enrollment into the study, if a serum pregnancy test is not performed within 7 days prior first IMP administration; a confirmatory urine test is required. Exclusion Criteria: * Indications for treatment of CLL (advanced stages of the disease) * Having receiving chemotherapy for CLL within 3 months prior to enrollment * Having received antiviral drugs or i.v. immunoglobulins within 3 months prior to enrollment * Significant thrombocytopenia (<100.000/µl) or anemia (Hb < 11 g/dl) * Women of child bearing age not using effective contraception * Pregnant of lactating female (as determined by a positive pregnancy test at screening or within 7 days prior to first IMP administration) * Known hypersensitivity to drug or its excipients

Study Objectives The purpose of this observational study is to assess HRQoL in relapsed and/or refractory multiple myeloma (RRMM) participants who have previously received a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody. Conditions: Multiple Myeloma Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Must have sufficient command of the Japanese language to understand the study instructions and requirements * Must be a resident of Japan * Must have received prior treatment with: 1. a proteasome inhibitor, 2. an immunomodulatory agent, and 3. an anti-CD38 antibody Subjects must be either 2-4 months, 5-7 months, or 8-11 months post triple class therapy exposure at time of consent * Subject must be diagnosed with multiple myeloma Exclusion Criteria: * Participants enrolled in a clinical trial that includes at least one novel/ experimental agent at the point of questionnaire completion Other protocol-defined inclusion/exclusion criteria apply.

Study Objectives The study is looking at the efficacy of subcutaneously administrated denosumab 60 mg every 6 months versus placebo after 3 years, by analyze of lumbar spine bone mineral density (BMD) in systemic mastocytosis. Investigators hypothesize that use of denosumab subcutaneously in patients with osteoporosis related to systemic mastocytosis is effective and safe to improve bone mineral density and prevent new bone events, based on targeted specific RANKL secretion by mast cells and short half-life of denosumab. Conditions: Osteoporosis, Systemic Mastocytosis Intervention / Treatment: DRUG: Denosumab, DRUG: Placebo Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Male or female >= 18 years of age at time of informed consent * Willingness and ability to sign informed consent, comply with scheduled visits, treatment plan, laboratory tests and other study procedures. * Patient with Indolent systemic or cutaneous mastocytosis according to WHO criteria (Appendix 4) with any specific treatment including corticosteroid, chemotherapy and immunomodulating drugs. * Patient with: * osteoporosis defined as bone mineral density T score <= -2.5 at the lumbar spine, OR * osteopenia defined as BMD T-score >-2,5 and <= -1 at the lumbar spine and low energy fracture (defined as fractures that are associated with decreased bone mineral density. Are excluded fractures of skull, face, mandible, metacarpals, fingers, or toes, pathologic fracture, and fracture that are associated with severe trauma). (in case of osteoarthritis at the lumbar spine, the T score at left femoral neck or total left hip can be used to define osteoporosis or osteopenia) Exclusion Criteria: * Patient with aggressive mastocytosis or/and Associated Hematologic Non-Mastocytosis Disease (AHNMD) * Patient with conditions that influence bone metabolism (primitive hyperparathyroidism, hyperaldosteronism, hypercorticism, etc ...) * Patient treated with intravenous bisphosphonate within 1 year prior to enrolment or with any other antiosteoporotic treatment within 3 months before enrolment. (per os bisphosphonate, strontium ranelate) Calcium and vitamin supplementation will be accepted * Patient previously treated with denosumab * Patient with hypocalcemia and/or hypo25-hydroxyvitamin D level non substituted prior enrolment * Woman without contraceptive treatment if of childbearing age. * Pregnant or breastfeeding woman * Patient with contraindication to denosumab * Patient with medical, psychiatric or other conditions that may interfere with patient safety * Patient with dental problem that need any dental surgery within 6 months after enrolment. * Patient with clearance of creatinine less than 30 mL/min/1,73m2 (MDRD) or patient receiving dialysis

Study Objectives The purpose of this study is to find out if a combination of drugs (these are called: cyclophosphamide, sirolimus, and mycophenolate mofetil) will protect participants better against graft vs. host disease (GVHD) after receiving a hematopoietic cell transplant from a related partially matched (haploidentical) donor. As part of the treatment for their blood cancer, participants need a hematopoietic cell transplantation (HCT) to improve their chances of cure. In any HCT, after the stem cell infusion is given, a combination of drugs is needed to prevent GVHD and facilitate acceptance of the graft. Conditions: Non-Hodgkin's Lymphoma, Acute Leukemia in Remission, Chronic Myeloid Leukemia, Primary Myelofibrosis, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndromes, Hodgkin Lymphoma, Multiple Myeloma Intervention / Treatment: DRUG: Fludarabine, DRUG: Busulfan, DRUG: Cyclophosphamide, RADIATION: Total body irradiation (TBI), PROCEDURE: Peripheral Blood Hematopoietic Cell Transplantation (HCT), DRUG: Sirolimus (SIR), DRUG: Mycophenolate mofetil (MMF), DRUG: Granulocyte-colony stimulating factor (G-CSF) Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: PREVENTION Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: Patient Participants: * Age: Must be older than 18 years, no upper age limit. * Karnofsky performance status: Full intensity conditioning, 80-100%; reduced intensity conditioning, 60-100%. * Vital organ function: a) Cardiac: Left ventricular ejection fraction must be > 45% assessed by multigated acquisition (MUGA) scan or echocardiogram. No myocardial infarction within 6 months of transplant evaluation. b) Pulmonary: forced expiratory volume at one second (FEV1), forced vital capacity (FVC), and adjusted diffusing capacity of the lungs for carbon monoxide (DLCO) must be >= 50% of predicted values. c) Liver: Transaminases (AST, ALT) less than 2 times upper limit of normal values. d) Kidney: Estimated creatinine clearance >= 50 cc/min. * Signed informed consent. * Included disease conditions and remission status: a) Acute leukemia in First Complete Remission (CR1) or second/subsequent CR. b) Chronic myeloid leukemia, primary myelofibrosis, chronic myelomonocytic leukemia. c) Int-2 or high risk myelodysplastic syndrome (MDS). d) Hodgkin lymphoma beyond CR1 with chemosensitive disease, Stable Disease (SD) may be included if no mass >3 cm. e) Non-Hodgkin lymphoma in high risk CR1 or subsequent CR (by clinical, cytogenetic or molecular criteria), primary induction failure (PIF) or relapsed with chemosensitive disease. SD may be included if no mass >3 cm. f) Multiple myeloma in CR/Very Good Partial Response (VGPR). Donor Participants: * Per Moffitt Cancer Center (MCC) Blood and Marrow Transplant (BMT) program practices, an allele level matched (8/8 HLA A, B, C and DR) sibling or unrelated donor is preferred. If a matched donor is not found, mismatched unrelated or haploidentical donors may be considered. * If a haploidentical donor is considered, parents, children, full siblings and in selected cases, extended family, will have high resolution typing at the MCC HLA laboratory. A familiar haploidentical donor is chosen among those who share at least one HLA-A, B, C, DRB1 and DQB1 haplotype with the patient. * Patient will be screened for antibodies targeting mismatched HLA antigens in potential haploidentical donors (donor specific antibodies, DSA). Antibody screen and confirmatory testing using Luminex single antigen-bead test will be done. * Among several potential donors, will choose in order of priority: a) Matched cytomegalovirus (CMV) immunoglobulin G (IgG) serologic status between donor and recipient. b) ABO blood group system-matched donor preferred, then minor ABO mismatch, then major ABO mismatch. c) Younger donor preferred: child, then sibling, and then parent. d) For male recipient, male donor will be preferred. Avoid mother as a donor unless no other choices. Exclusion Criteria: Patient Participants: * Uncontrolled active bacterial, viral, fungal infection. * Prior allogeneic HCT. * Unwilling to comply with study requirements. * Active, progressive or advanced disease based on diagnosis.

Study Objectives This phase II trial studies donor atorvastatin treatment for the prevention of severe acute graft-versus-host disease (GVHD) in patients undergoing myeloablative peripheral blood stem cell (PBSC) transplantation. Giving chemotherapy and total-body irradiation (TBI) before a donor PBSC transplant helps stop the growth of cancer cells. It may also prevent the patient's immune system reject the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving atorvastatin to the donor before transplant may prevent this from happening. Conditions: Malignant Neoplasm Intervention / Treatment: PROCEDURE: Allogeneic Hematopoietic Stem Cell Transplantation, DRUG: Atorvastatin Calcium, PROCEDURE: Peripheral Blood Stem Cell Transplantation Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: SUPPORTIVE_CARE Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Human leukocyte antigen (HLA)-identical sibling donor * Myeloablative preparative regimen (i.e., >= TBI 12.0 Gy, >= busulfan (BU) 8.0 mg/kg PO, >= BU 6.4 mg/kg intravenously (IV), >= treosulfan 42 g/m^2 IV) according to investigational study or standard treatment plan; other "myeloablative" preparative regimens are acceptable as long as they are approved by the principal investigator or designee * Transplantation of PBSC * Cyclosporine (CSP)-based postgrafting immunosuppression * Willingness to give informed consent * DONOR: Age >= 18 years * DONOR: HLA genotypically identical sibling * DONOR: Willingness to give informed consent Exclusion Criteria: * Nonmyeloablative preparative regimen * Participation in an investigational study that has acute GVHD as the primary endpoint * The allogeneic PBSC donor has a contraindication to statin treatment * DONOR: Age < 18 years * DONOR: Active liver disease (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] levels > 2 times the upper limit of normal [ULN]) * DONOR: History of myopathy * DONOR: Hypersensitivity to atorvastatin * DONOR: Pregnancy * DONOR: Nursing mother * DONOR: Current serious systemic illness * DONOR: Concurrent treatment with strong inhibitors of hepatic cytochrome P450 (CYP) 3A4 (i.e. clarithromycin, erythromycin, protease inhibitors, azole antifungals) * DONOR: Current use of statin drug * DONOR: Failure to meet Fred Hutchinson Cancer Research Center (FHCRC) or local criteria for stem cell donation * DONOR: Total creatinine kinase > 2 times the ULN

Study Objectives A prospective, multicenter, open label, randomized phase III study to evaluate efficacy and safety of FFX versus CPI-613 + mFFX in patients with metastatic adenocarcinoma of the pancreas with age range of 18 to 75 years Conditions: Pancreatic Cancer Metastatic Intervention / Treatment: DRUG: CPI 613, mFolfirinox, DRUG: Folfirinox Location: Israel, Germany, Korea, Republic of, 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: * Histologically or cytologically confirmed metastatic Stage IV adenocarcinoma of the pancreas * No prior treatments for stage IV pancreatic adenocarcinoma (prior adjuvant or neoadjuvant treatment is allowed provided completed > 6 months prior to disease recurrence) * Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1 * Male and female patients 18 - 75 years of age * Measurable disease determined using guidelines of Response Evaluation Criteria In Solid Tumors (RECIST version 1.1) * Expected survival >3 months * Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted highly effective contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive(s), intrauterine hormone releasing system (IUS), bilateral tubal occlusion or vasectomized partner) during and for 6 months after last study dose and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation, at monthly interval (day 1 of every even numbered cycle), at the end of systemic exposure, and at 30 days after the systemic exposure * Males with female partners (of childbearing potential) and female partners (of child bearing potential) with male partners must agree to use double barrier contraceptive measure (a combination of male condom with either cap, diaphragm or sponge with spermicide) in addition to oral contraception or avoidance of intercourse during the study and for 6 months after last study dose is received * At least 2 weeks must have elapsed from any prior surgery with resolution of any sequela for randomization * Laboratory values <=2 weeks prior to randomization must be: * Adequate hematologic values * Platelet count >=100,000 cells/mm3 or >=100 bil/L; * Absolute neutrophil count [ANC] >=1,500 cells/mm3 or >=1.5 bil/L; * Hemoglobin >=9 g/dL or >=90 g/L) * Adequate hepatic function * Aspartate aminotransferase [AST/SGOT] <=3x upper normal limit [UNL] (<=5x UNL if liver metastases present) * Alanine aminotransferase [ALT/SGPT] <=3x UNL (<=5x UNL if liver metastases present) * Bilirubin (<=1.5x UNL); bilirubin <= 2.5 x ULN for subjects with Gilbert's syndrome * Serum albumin > 3.0 g/dL * Adequate renal function serum creatinine clearance CLcr > 30 mL/min). (Cocroft-Gault Formula should be used for CrCl calculation) * Adequate coagulation function * International Normalized Ratio or INR must be <1.5 unless on therapeutic blood thinners) * No evidence of active infection and no serious infection within the past 30 days. * Mentally competent, ability to understand and willingness to sign the informed consent form. Exclusion Criteria: * Endocrine or acinar pancreatic carcinoma * Known cerebral metastases, central nervous system (CNS), or epidural tumor * Prior treatment with any chemotherapy for metastatic adenocarcinoma of the pancreas * Completion of a gemcitabine-based adjuvant chemotherapy regimen within less than 6 months at the time of screening. * Receipt of neoadjuvant or adjuvant FOLFIRINOX therapy if <6 months prior to disease recurrence * Patients with hypersensitivity to devimistat, FFX treatment or any of their excipients * Presence of clinically significant abdominal ascites * Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication within the past 2 weeks prior to initiation of devimistat treatment * Serious medical illness that would potentially increase patients' risk for toxicity * Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease) * Female patients who are pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 6 months after the last dose of study treatment * Female patients of childbearing potential with a positive pregnancy test assessed by a serum pregnancy test at screening * Female patients of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for 6 months after the last dose of study treatment * Male patients with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for 6 months after completion of study treatment * Male patients unwilling to abstain from donating sperm during treatment and for 6 months after completion of study treatment * Life expectancy less than 3 months * Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients * Unwilling or unable to follow protocol requirements * Active heart disease including but not limited to symptomatic congestive heart failure (NYHA class 3 or 4), symptomatic coronary artery disease, symptomatic angina pectoris, or symptomatic myocardial infarction * Patients with a history of myocardial infarction that is <3 months prior to registration * Evidence of active infection, or serious infection within the past 30 days. * Patients with known HIV infection * Patients who have received cancer immunotherapy of any type within the past 2 weeks prior to initiation of devimistat treatment (steroids given for supportive care or in response to allergic reactions are allowed at any time) * Requirement for immediate palliative surgery, radiation or chemotherapy of any kind. Stenting for bile duct obstruction and need for pain medications are allowed provided all other inclusion criteria are met * Prior malignancy except for the following: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated cancer from which the patient has been disease-free for at least 3 years prior to screening * Unwilling or unable to avoid the concomitant use of strong CYP3A4 inducers or inhibitors during treatment with irinotecan * A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 480 milliseconds (ms) (CTCAE grade 1) using Fredericia's QT correction formula (i.e. QTcF) * A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of long QT syndrome) * The use of concomitant medications that prolong the QT/QTc intervals * Contraindications to any of the FFX treatment as follows: Folinic Acid * Calcium Folinate is contraindicated in patients who have previously shown hypersensitivity to folinate or any of the excipients. * Calcium Folinate Injection is contraindicated in the treatment of pernicious anemia or other megaloblastic anemias where vitamin B12 is deficient. Its use can lead to an apparent response of the hematopoietic system, but neurological damage may occur or progress if already present. * Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take calcium folinate tablets. Fluorouracil/5FU * Fluorouracil is contraindicated in patients who have any known hypersensitivity to fluorouracil, are seriously debilitated or are suffering from bone marrow depression after radiotherapy or treatment with other antineoplastic agents, or who are suffering from a potentially serious infection. * Fluorouracil is strictly contraindicated in pregnant or breast-feeding women. * Flourouracil should not be used in the management of non-malignant disease. * Fluorouracil must not be taken or used concomitantly with brivudin, sorivudine and analogues. Brivudin, sorivudine and analogues are potent inhibitors of the enzyme dihydropyrimidine dehydrogenase (DPD) which degrades fluorouracil * In patients with known complete absence of dihydropyrimidine dehydrogenase (DPD) activity Oxaliplatin * Oxaliplatin is contraindicated in patients who have a known history of hypersensitivity to oxaliplatin or to any of the excipients * are breast-feeding. * have myelosuppression prior to starting first course, as evidenced by baseline neutrophils <2x109/l and/or platelet count of <100x109l. * have a peripheral sensitive neuropathy with functional impairment prior to first course. * have a severely impaired renal function (creatinine clearance less than 30 ml /min) Irinotecan * Chronic inflammatory bowel disease and/or bowel obstruction * History of severe hypersensitivity reactions to Irinotecan hydrochloride trihydrate or to any of the excipients * Bilirubin > 3 times the ULN * Severe bone marrow failure. * WHO performance status > 2. * Concomitant use with St John's wort

Study Objectives The purpose of this study is to determine if the addition of daratumumab to lenalidomide-bortezomib-dexamethasone (RVd) will increase the proportion of participants achieving stringent complete response (sCR), as defined by the International Myeloma Working Group (IMWG) criteria, by the time of completion of post autologous stem cell transplantation (ASCT) consolidation treatment, compared with RVd alone. Conditions: Multiple Myeloma Intervention / Treatment: DRUG: Lenalidomide, DRUG: Bortezomib, DRUG: Dexamethasone, DRUG: Daratumumab Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Considered by the investigator to be eligible for high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) according to the institution's criteria based on age, medical history, cardiac and pulmonary status, overall health and condition, co-morbid condition(s), physical examination, and laboratory studies * Has not had prior systemic therapy for multiple myeloma. An emergency course of steroids (defined as no greater than 40 milligram [mg] of dexamethasone, or equivalent per day for a maximum of 4 days (that is, a total of 160 mg) is permitted. In addition, radiation therapy is permitted prior to study entry, during screening, and during Cycles 1-2 of study treatment as needed for lytic bone disease * Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 * Woman of childbearing potential must have 2 negative highly sensitive serum (beta-human chorionic gonadotropin [b-hCG]) during screening, the first one within 10 to 14 days prior to the first dose of any component of study treatment and the second within 24 hours prior to the first dose of any component of study treatment * A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study (including during dose interruptions), and for 4 weeks following discontinuation of lenalidomide, and if receiving daratumumab, for 3 months after the last dose Exclusion Criteria: * Diagnosed or treated for malignancy other than multiple myeloma, except: a) Malignancy treated with curative intent and with no known active disease present for more than equal to (>= )3 years before randomization; b) Adequately treated non-melanoma skin cancer, lentigo maligna or in situ malignancies (including but not limited to, cervical, breast) with no evidence of disease * Exhibiting clinical signs of or has a known history of meningeal or central nervous system involvement by multiple myeloma * Known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) less than (<)50 percent (%) of predicted normal * Known moderate or severe persistent asthma within the past 2 years or currently has uncontrolled asthma of any classification * Known to be seropositive for human immunodeficiency virus, known to have hepatitis B surface antigen positivity, or known to have a history of hepatitis C. Participants who completed treatment for hepatitis C at least 6 months prior to screening and have no detectable circulating hepatitis C virus (HCV) at screening, may participate in the study. Such participants will be required to undergo regular assessment for HCV reactivation during their participation in the study. Participants who test positive for HCV at any time during these assessments will be withdrawn from the study

Study Objectives Persistent insomnia is highly prevalent complaint in cancer survivors, but is seldom satisfactorily addressed. The adaptation to cancer care of a validated, cost-effective intervention may offer a practicable solution. The aim of this study was to investigate the clinical effectiveness of homeopathy for insomnia. Conditions: Chronic Insomnia, Cancer Intervention / Treatment: OTHER: Homeopathy Medicine Location: India Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * scheduled to begin chemotherapy or radiotherapy * chemotherapy or radiotherapy * meet diagnostic criteria for chronic insomnia (i.e., lasting for at least one month) * Chronic insomnia has been defined in previous research:as the presence of (1) three or more episodes of insomnia (i.e., >= 30minuteSOL, >= 60minute wake after sleep onset (WASO), or <= 6.5 hour total sleep time (TST) per night) of per week and (2) daytime effects of insomnia, such as irritability, difficulty concentrating, or fatigue for at least one month. * have the permission of their oncologists to participate. Exclusion Criteria: * untreated alcohol or substance abuse or dependence, * bipolar, or psychotic disordermedical conditions such as seizure disorder, restless leg disorder, or Parkinson's disease * untreated sleep disorders such as sleep apnea * Taking other alternative medicines

Study Objectives The purpose of this investigational trial is to find out how well patients respond and how long their response lasts when treated with a standard regimen of dexamethasone with or without thalidomide and also find out what kind of side effects patients will experience. Conditions: Multiple Myeloma Intervention / Treatment: DRUG: Thalidomide, DRUG: Dexamethasone Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * All patients must have a confirmed diagnosis of previously treated, active multiple myeloma, with hypoproliferative/low risk relapse following at least one autologous transplant. * Patients must be 18 years of age or older. Women of childbearing age and fertile men must use a medically acceptable means of birth control while on study and for 6 months thereafter. * Patients must sign an informed consent to participate in this study, and be fully aware of the known teratogenic potential of this drug combination. * Patients must have a SWOG performance status of 0-2. * Patients must have adequate renal function, as defined by serum creatinine < or = 3.0 mg/dl. * Patients must be off chemotherapy (including steroids) and local radiotherapy for > or equal 3 weeks prior to entering the study. Exclusion Criteria: * No other concurrent therapy for myeloma is permitted while on protocol. * There must be no evidence of active infection requiring IV antibiotics.

Study Objectives Open-label, non-randomized, Phase I, dose-escalating, first-in-man study. Conditions: Solid Tumor Intervention / Treatment: DRUG: ICP-105 Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: * 18 Years and older. * Eastern Cooperative Oncology Group (ECOG) performance status <= 1. * At least one evaluable disease according to RECIST1.1. * Histologically or cytologically confirmed solid tumors, failure to respond to standard therapy, or for whom standard therapy does not exist. * Adequate bone marrow, liver, renal, and cardiovascular function. Exclusion Criteria: * Previous treatment with FGF19, FGFR4 inhibitors and/or pan-FGFR inhibitors. * Anti-cancer therapy, such as chemotherapy, immunotherapy, hormonal, targeted therapy, or investigational agents within four weeks of the first dose of ICP-105. * Major surgery within 6 weeks of the first dose of ICP-105. * Significant GI disorder(s) that could interfere with the absorption, metabolism, or excretion of ICP-105. * Crohn's disease with symptoms and systemic treatment. * Central nervous system (CNS) metastasis. * Current clinically significant cardiovascular disease including: * Any class 3 or 4 cardiac disease such as arrhythmia, congestive heart failure or myocardial infarction defined by the New York Heart Association Functional Classification, or left ventricular ejection fraction (LVEF) < 50%, Primary cardiomyopathy, clinical significant QTc prolong history or QTc>470ms (female) QTc>450ms (male). * Known active bleeding within 2 months of screening or 6 months of bleeding history. * Lung function impairment by pleural effusion or ascites, any history of interstitial pneumonia, deep vein thrombosis, pulmonary embolism. * Known active infection with HBV, HCV or HIV or any uncontrolled active systemic infection. * Non-hematological toxicity must recover to <= Grade 1 from prior anti-cancer therapy (excluding alopecia, nausea and vomiting). * Lactating or pregnant women, or women who will not use contraception during the study and for 180 days after the last dose of study drug if sexually active and able to bear children.

Study Objectives The purpose of this study is to find the best and most sensitive screening modality (CT, MRI, EUS)for very small pre-cancerous pancreatic lesions and to treat these small lesions before they turn into cancer. Another purpose of this study is to search for common markers on DNA that would increase the chance of someone developing pancreatic cancer, and locate proteins in pancreatic juice that indicate tumor development. Conditions: Pancreatic Neoplasm, Peutz-Jeghers Syndrome Intervention / Treatment: PROCEDURE: Biopsy, Fine Needle Aspiration (FNA), DRUG: Secretin (human synthetic) - ChiRhoClin Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Persons with a verified family history of 2 or more first degree relatives with primary site pancreatic cancer(PC), age 40-80 years old or if 1 first degree relative also has at least 2 second degree relatives affected with PC. * Persons with a verified BRCA2 gene mutation or FAMM/p16 gene mutation, age 40-80 years old, and family history of pancreatic cancer. * Persons with Peutz-Jeghers Syndrome, 30-80 years old, and family history of pancreatic cancer. Exclusion Criteria: * Persons with pancreatic cancer, or suspicious symptoms. * Persons who have had pancreas specific imaging protocol performed in the past three years. * Persons medically unable to have an endoscopy, CT or MRI procedure

Study Objectives The purpose of this study is to evaluate the safety and tolerability of selected dose 1.2mg/kg BID dosage administered subcutaneously (SC) administered PCI-27483 to metastatic or locally advanced pancreatic cancer patients receiving concurrent therapy with intravenously administered gemcitabine for 12 weeks. Conditions: Pancreatic Cancer, Ductal Adrenocarcinoma, Exocrine Pancreatic Cancer Intervention / Treatment: DRUG: PCI-27483, DRUG: Gemcitabine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Men or women at least 18 years old * Body weight >= 40 and <= 100 kg. * Part A: Metastatic ductal adenocarcinoma of the pancreas diagnosed <= 4 months prior to enrollment. (Locally advanced does not have any criteria) * Part B: Locally advanced ductal adenocarcinoma of the pancreas diagnosed <= 3 months prior to enrollment or metastatic ductal adenocarcinoma diagnosed <= 2 months. * Measurable disease by spiral CT scan (SCT) in accordance with RECIST criteria. * Patients after non-curative surgery are eligible if at least 4 weeks after surgery and recovered from significant surgical morbidity. * Estimated life expectancy of at least 4 months. * ECOG performance status 0 to 1. * Normal baseline coagulation function as defined by: 1. PT 10-16 seconds, and 2. aPTT 22-38 seconds. * Agree to not participate in contact sports or strenuous activity while taking PCI-27483. * Ability to understand the study, willingness to participate in the study for the study duration, and ability to provide written informed consent to participate. Exclusion Criteria: * History of any clinically significant medical condition that, in the opinion of the Principal Investigator, would interfere with the study evaluation or interpretation. * Known history of brain metastases. * Any evidence of intra-cranial hemorrhage based on head CT scan within 30 days of enrollment. * History of disease progression while being treated with gemcitabine. * Radiotherapy of the primary tumor or unwillingness to defer radiotherapy of the primary tumor until > 3 months from initiation of treatment. * History of venous thromboembolism (eg, deep vein thrombosis, pulmonary embolism,and arterial thromboembolism) or other indications for anticoagulant treatment (eg,mechanical heart values, atrial fibrillation, etc.) within the last year. Local thrombus in the mesenteric or portal vein is acceptable. * Uncontrolled hypertension (systolic > 160 or diastolic > 100 mm Hg on medical treatment). * Continued anticoagulation therapy or anticoagulation therapy within 2 months prior to enrollment, except for perisurgical prophylaxis which must have ceased 2 weeks before enrollment. * Contraindication to systemic anticoagulation. * Continued treatment with antiplatelet drugs including aspirin, clopidogrel, etc. within the past 72 hours. * Known history of clinically significant or recurrent bleeding episodes, including significant bleeding after surgery, childbirth, or dental extraction. * Patients with documented invasion of adjacent organs by CT scan (e.g. stomach, duodenum) are not eligible * Patients known to have esophageal varicose are not eligible * Known history of a congenital coagulation factor deficiency. * Known acquired or hereditary platelet disorder. * Known history of immunodeficiency. * Women of child-bearing potential or sexually active men, unwilling to use adequate contraceptive protection during the course of the study. * Pregnant or lactating women (female patients of childbearing potential must have a negative serum pregnancy test within 14 days of first day of drug dosing, or if positive, pregnancy ruled out by ultrasound). * Laboratory Abnormalities: 1. Serum creatinine > 2 mg/dL or creatinine clearance < 50 mL/minute (using Cockroft Gault formula) 2. AST and ALT >= 4.0 x upper limit of normal (ULN). 3. Bilirubin >= 3 mg/dL. 4. Alkaline phosphatase > 5 x ULN. 5. Albumin < 2.0g/dL. 6. Hemoglobin < 9.0 g/dL. 7. Platelet count < 100,000/μL. * Evidence of active gastrointestinal tract bleeding, including guaiac stool positivity,excluding hemorrhoidal bleeding * Chronic active hepatitis B or C. * Known HIV infection. * Participation in any study of an investigational device, medication, biologic, or other agent within 30 days prior to enrollment, or planned participation within the study duration. * Risk factors for, or use of medications known to prolong QTc interval or that may be associate with Torsades de Pointes within 7 days of treatment start (see Appendix J. Risk Factors for Drug-induced Torsades de Pointes). * QTc prolongation (defined as a QTc >= 450 msec) or other significant ECG abnormalities including 2nd degree AV block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min). If 2 screening ECGs have a QTc >= 450 msec, the ECGs can be submitted for a centralized, cardiologic evaluation and if determined to be < 450 msec then the patient is eligible.

Study Objectives In this research study, we are looking at the anti-tumor effects of Cabozantinib (XL184) in metastatic breast cancer. Data suggest that MET expression and activation are important for initiation and progression of triple-negative breast cancer (TNBC). We evaluated the efficacy of cabozantinib (XL184), a novel inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2, in patients with metastatic TNBC. Conditions: Breast Cancer Intervention / Treatment: DRUG: Cabozantinib Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed invasive breast cancer with stage IV disease * Primary tumor and/or metastasis must be ER-negative, PR-negative and HER2-negative * May have received 0-3 prior chemotherapeutic regimens for metastatic breast cancer. Must be off treatment for at least 21 days prior to enrollment * Must have discontinued all biologic therapy at least 14 days before enrollment * May have received prior radiation therapy in the early stage or metastatic setting, but must have completed treatment at least 14 days prior to enrollment * Must agree to use medically acceptable methods of contraception * Confirmed availability of formalin-fixed, paraffin-embedded tumor tissue * Able to swallow tablets Exclusion Criteria: * Pregnant or breastfeeding * Received another investigational agent within 14 days prior to enrollment * Received prior c-Met inhibitor * Known brain metastases that are untreated, symptomatic or require therapy to control symptoms * Psychiatric illness or social situation that could limit ability to comply with study requirements * Require concomitant treatment in therapeutic doses with anticoagulants or antiplatelet agents * Diagnosis of another malignancy requiring systemic treatment within the last two years (except non-melanoma skin cancer or in-situ carcinoma of the cervix) * Known to be positive for HIV * Active infection requiring IV antibiotics at Day 1 of cycle 1 * Uncontrolled, significant intercurrent illness * Requires chronic concomitant treatment of a strong CYP3A4 inducer * tumor in contact with, invading or encasing major blood vessels * Have experienced clinically significant gastrointestinal bleeding within 6 months, hemoptysis of more than 0.5 teaspoon of red blood within 3 months or other signs indicative of pulmonary hemorrhage within 3 months of enrollment

Study Objectives Patients scheduled for a cystectomy at Charleston Area Medical Center (CAMC) will be enrolled into a randomized, double blinded clinical trial to assess if postoperative pain and ileus are reduced by perioperative intravenous lidocaine infusion versus placebo. The hypothesis is that patients receiving the lidocaine infusion will experience better pain control and ileus resolution. It is believed that lidocaine patients will also have less opioid requirement, less mortality, a shorter length of stay, less nausea /vomiting, and fewer adverse events. Conditions: Invasive Bladder Cancer Intervention / Treatment: PROCEDURE: Cystectomy, DRUG: Lidocaine, DRUG: Saline Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Any patient undergoing a cystectomy with an American Society of Anesthesiologists physical status classification (ASA) of 1 or 2. Exclusion Criteria: * Any patients with a history of substance abuse, allergy to amides, and current treatment with antiarrhythmic medications (due to lidocaine being a class 1b antiarrhythmic agent) will be excluded. * Patients will also be excluded if they are pregnant or have a history of chronic pain syndrome, chronic bowel or liver dysfunction. * Patients with chronic opioid use, and therefore opioid tolerance, and history of opioid addiction will also be excluded due to likely increased opioid needs for equivalent pain control.

Study Objectives A phase I-II study of treatment of metastatic melanoma using induction therapy with Biochemotherapy plus Bevacizumab followed by consolidation therapy with Ipilimumab (BBI). Conditions: Metastatic Melanoma Intervention / Treatment: DRUG: Biochemo + bevacizumab then ipilimumab 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: * Stage 4 or unresectable stage 3 metastatic melanoma with or without measurable disease * Age 18-70 years old * Adequate pulmonary and cardiac function for high-dose IL-2 * PS 0-2 * Previous ipilimumab therapy will not exclude patients, but patients with previous ipilimumab will have separate efficacy analysis Exclusion Criteria: * Brain metastases * Creatinine > 2x ULN; bilirubin > 3, WBC < 3500, Platelets < 100,000, Hgb < 9 * Another active malignancy * Gastrointestinal tract metastases except rectal metastases or primary are allowable * Previous therapy for metastatic disease with chemotherapy of duration over 3 months or with high-dose interleukin-2 * History of colitis or autoimmune disease such as lupus or rheumatoid arthritis * Bevacizumab-related contraindications: Hemoptysis or history of severe bleeding, uncontrolled hypertension, proteinuria with protein/creatinine ratio > 1, acute myocardial infarction within 6 months

Study Objectives Endoscopic submucosal dissection is commonly performed under light to moderate sedation, and minimizing patient movement is of key importance for successful outcome. Propofol has widely replaced benzodiazepines as sedative drug of choice, and has been reported to enhance the quality of procedure in our past study. However, despite higher satisfaction scores of the endoscopists and faster post-procedural recovery, patient satisfaction scores were found to be higher in patients that received midazolam and meperidine instead of propofol and remifentanil. This seems to be due to the anterograde amnestic effects of midazolam rather than the quality of sedation itself. Investigator hypothesized that by premedicating the patient with low lose midazolam before receiving sedation for ESD with propofol and fentanyl, patient satisfaction would be enhanced without affecting endoscopic performance. Conditions: Early Gastric Cancer, Gastric Adenoma Intervention / Treatment: DRUG: midazolam 0.02mg/kg, DRUG: No premedication Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Adult patients over the age of 19 diagnosed with early gastric cancer or gastric adenoma that are scheduled for endoscopic submucosal dissection * American society of anesthesiologist physical status 1~3 Exclusion Criteria: * Patient refusal * Patients that received sedatives within 24 hours prior to endoscopic submucosal dissection * History of gastrectomy or previous endoscopic submucosal dissection at same site * Allergies to propofol or its ingredients, soybeans or peanuts * Pregnant or breastfeeding patients * Patients with severe debilitating underlying medical conditions * Patients with altered mental status * Illiterate patients or foreigners

Study Objectives This is: * A prospective, randomized, open, phase II, multi-centre, interventional study. Patients who are in at least PR and have received lenalidomide as 2nd line treatment for MM will be recruited. * The patients will be randomized into two groups. Group R will receive lenalidomide 25 mg/day p.o. continuously for 21 days and group Rb will receive a similar dose of lenalidomide with the addition of 40 mg of dexamethasone p.o. on days 1, 8, 15 and 22 of every 28 day treatment cycle. Study includes a maximum of 24 cycles including two consolidating cycles per patients. Conditions: Multiple Myeloma Intervention / Treatment: DRUG: Revlimid Location: Sweden Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: Inclusion Criteria - all subjects must: * Be at least 18 years of age * Subjects must have a documented diagnosis of MM and have either refractory or relapsed and refractory after first line treatment disease defined as: * Primary refractory * Refractory * Relapsed and Refractory * Subjects must have undergone prior treatment with one treatment line of anti-myeloma therapy. Induction therapy followed by ASCT and consolidation/maintenance will be considered as one line.Have a confirmed diagnosis of MM * Have received lenalidomide after one prior treatment for MM and have reached at least a partial response (PR), according to IMWG criteria, including two consolidating cycles. Subjects have experienced a response at least PR after starting treatment with lenalidomide and cortisone cycles. * Have personally signed and dated a legally effective written informed consent form prior to admission to the study. * Must be willing and able to understand and comply with the study requirements. * Females of childbearing potential must agree to ongoing pregnancy testing and to practice contraception. * Male must agree to practice contraception Exclusion Criteria: * Any of the following laboratory abnormalities: * Absolute neutrophil count (ANC) < 1,000/µL * Platelet count < 75,000/ µL * Creatinine Clearance < 45 mL/min according to Cockcroft-Gault formula * Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN) * Serum total bilirubin > 2.0 mg/dL * ECOG performance status <4. * Individuals who have had a stem-cell transplant as a 2nd line treatment for MM * Individuals who have taken any experimental drugs or participated in a clinical trial within 30 days prior to screening. * Individuals with significant psychiatric illness or a clinically significant acute/chronic uncontrolled medical condition that might affect their experience of myeloma symptoms or their ability to describe them. * Pregnant or lactating females. * Any other clinically significant medical disease or condition that, in the Investigator´s opinion, may interfere with protocol adherence or a subject´s ability to give informed consent.

Study Objectives To evaluate the safety profile of Genexol PM combination with carboplatin for patients with newly diagnosed ovarian cancer. We hypothesized Genexol PM can be safely administered to newly diagnosed ovarian cancer patients compared to conventional paclitaxel/carboplatin combination therapy. Therefore, we will compare the prospective cohort with a historical comparison with patients administered paclitaxel/carboplatin and paclitaxel/carboplatin/bevacizumab combination therapy. Conditions: Ovarian Cancer Intervention / Treatment: DRUG: Genexl PM Location: Korea, Republic of Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Age over 18 * Patients consented to participate * Pathologically diagnosed ovarian cancer FIGO stage IC-IVB * ECOG 0-2 * Patients with an expected survival of 3 months or more Exclusion Criteria: * History of paclitaxel or carboplatin hypersensitivity * Inadequate bone marrow function (Neutrophil<1500/mm3, Platelet <100,000/mm3) * Pregnancy or breast-feeding state * Metachronous or synchronous malignancy * Galactose intolerance, Lapp Lactase deficiency, or glucose-galactose malabsorption patients with genetic problems * Other patients who were judged difficult to be included in this investigation by the investigator in charge

Study Objectives The purpose of this study is to see the effect of PEP02 in the treatment of metastatic pancreatic cancer. Conditions: Pancreatic Neoplasms Intervention / Treatment: DRUG: PEP02 Location: United States, Taiwan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed adenocarcinoma of exocrine pancreas * Metastatic disease * Documented disease progression after treatment with 1 line of prior gemcitabine-based regimen * Karnofsky performance status equal or more than 70 Exclusion Criteria: * With active CNS metastases * With clinically significant gastrointestinal disorder (e.g., bleeding, inflammation, occlusion, or diarrhea > grade 1) * Major surgery or radiotherapy within 4 weeks * Prior participation in any investigational drug study within 4 weeks * With prior irinotecan treatment

Study Objectives The goal of this clinical research study is to find the highest tolerable dose of BKM120 that can be given to patients with relapsed or refractory leukemia. The safety of BKM120 will also be studied. Conditions: Leukemia Intervention / Treatment: DRUG: BKM120 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 old or older * Relapsed/refractory leukemias for which no standard therapy options are anticipated to result in a durable remission: Acute myelogenous leukemia (AML) by World Health Organization (WHO) classification or acute lymphoblastic leukemia (ALL) relapsed or refractory to standard chemotherapy; unsuitable for standard chemotherapy or unwilling to undergo standard chemotherapy. Philadelphia chromosome (Ph) positive ALL eligible if failed prior tyrosine-kinase inhibitor therapy. Age =/> 60 years with AML not candidates for or have refused standard chemotherapy, excluding subjects with acute promyelocytic leukemia (APL) or with favorable cytogenetic abnormalities [inv16, t(8;21)]. * Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2 * Serum total bilirubin <= 2 x ULN or direct bilirubin <=ULN for patients with total bilirubin levels > 2 x ULN, unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis. Aspartate aminotransferase or alanine aminotransferase within normal range (or =/< 3.0 x upper limit of normal (ULN) if due to leukemic involvement); serum creatinine =/< 1.5 x ULN or 24-hour clearance =/> 50 mL/min; serum amylase <= ULN; serum lipase<= ULN. * Fasting glucose =/< 120 mg/dL (6.7 mmol/L). * Total calcium (corrected for serum albumin) within normal limits (8.8 - 10.5 MG/DL). This is MD Anderson Cancer Center (MDACC) lab standard. Supplements for calcium allowed to meet eligibility criteria. * Magnesium >= the lower limit of normal (1.8 MG/DL). Supplements for magnesium allowed to meet eligibility criteria * Potassium within normal limits (3.5 - 5.0 milliequivalent (MEq)/L). Supplements for potassium allowed to meet eligibility criteria * international normalized ratio (INR) =/< 2 * Women of childbearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum or urine pregnancy test within 48 hours prior to the start of study drug * Patients should be able to take oral medications. Exclusion Criteria: * Patients who have received myelosuppressive chemotherapy <= to 4 weeks prior to starting study drug (with the exception of Hydroxyurea which will be allowed during Course 1 of treatment). * Patients who have received targeted anticancer therapy <= 2 week (for non myelosuppressive therapy) prior to starting study drug. * central nervous system (CNS) disease * Patient has active cardiac disease including any of the following: Left ventricular ejection fraction (LVEF) < 50% as determined by Multiple Grated acquisition (MUGA) scan or echocardiogram (ECHO), corrected QT interval (QTc) > 480 msec on screening ECG (using the QTcF formula), Angina pectoris that requires the use of anti-anginal medication, Ventricular arrhythmias except for benign premature ventricular contractions, Supraventricular and nodal arrythmias requiring a pacemaker or not controlled with medication, Conduction abnormality requiring a pacemaker, Valvular disease with document compromise in cardiac function, Symptomatic pericarditis * Patient has a history of cardiac dysfunction including any of the following: Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function Documented congestive heart failure (New York Heart Association functional classification III-IV) Documented cardiomyopathy * Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., e.g., uncontrolled infection, such as persistent fever despite antibacterial therapy) that could cause unacceptable safety risks or compromise compliance with the protocol. Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusion capacity of lung for carbon monoxide (DLco), O2 saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates. * Patient has poorly controlled diabetes mellitus or steroid-induced diabetes mellitus * Patients with acute or chronic liver, renal disease or pancreatitis * Patients with diarrhea >= CTCAE grade 2 * Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). Patients with unresolved diarrhea will be excluded as previously indicated * Patients who have been treated with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) <= 2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued * Patients with the following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire: a. Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) b. >= CTCAE grade 3 anxiety c. Meets the cut-off score of >= 10 in the Patient Health Questionnaire PHQ-9 or a cut-off of >= 15 in the General Anxiety Disorder GAD-7 mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) will be excluded from the study unless overruled by the psychiatric assessment * Patients who have received prior treatment with a PI3K inhibitor * Patients with a known hypersensitivity to BKM120 or to its excipients * Patients who are currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug. Please refer to table 4-7 or a list of prohibited QT prolonging drugs with risk of Torsades de Pointes * Patients who are currently treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. If treatment with such an inhibitor is in the best interest of the patient, extreme caution should be taken with its concomitant use. Please refer to Table 4-6 for a list of prohibited inhibitors and inducers of CYP3A (Please note that co-treatment with weak inhibitors of CYP3A is allowed) * Patients receiving chronic treatment with steroids or another immunosuppressive agent * Patients who have taken herbal medications and certain fruits within 7 days prior to starting study drug. Herbal medications include, but are not limited to St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Fruits include the CYP3A inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits * Patients who have undergone major surgery <= 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy * Patients who are currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant * Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control. Double barrier contraceptives must be used through the trial by both sexes. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Women of child-bearing potential must have a negative serum or urine pregnancy test <= 48 hours prior to initiating treatment. * Known diagnosis of human immunodeficiency virus (HIV) infection * History of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix and squamous cell carcinoma in situ of the skin. * Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator.

Study Objectives The purpose of this study is to determine the pharmacodynamics effects of itraconazole in early-stage non-small cell lung cancer. Conditions: Non-small Cell Lung Cancer Intervention / Treatment: DRUG: Itraconazole Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: EARLY_PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically or cytologically proven NSCLC planned for surgical resection. All NSCLC histologic subtypes are eligible. Alternatively, patients in whom a diagnosis of NSCLC is highly suspected based on history and imaging studies and who are, therefore, scheduled for diagnostic biopsy and/or surgical resection will also be eligible for screening, enrollment, and study treatment if they meet all additional eligibility criteria. In the event that biopsies do not confirm NSCLC, such patients will be removed from study but monitored for any adverse events resulting from study participation. * No prior therapy but planned for surgical resection * Age >= 18 years. * ECOG (Eastern Cooperative Oncology Group) 0-2 performance status * Adequate organ function as defined below: * total bilirubin within normal institutional limits * AST (Aspartate Aminotransferase) (SGOT)/ALT (Alanine Aminotransferase) (SPGT) <= 2.5 X institutional upper limit of normal * creatinine <= 2 X institutional upper limit of normal * 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, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. 6.1 A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). * Ability to understand and willingness to sign a written informed consent. Exclusion Criteria: * Subjects may not be receiving any investigational agents that would confound interpretation of study pharmacodynamic endpoints. * History of allergic reactions attributed to itraconazole or to compounds of similar chemical or biologic composition to itraconazole. * Uncontrolled, concurrent medical illness. * Active hepatitis or symptomatic liver disease. * History of or current evidence of uncontrolled cardiac ventricular dysfunction (congestive heart failure) or NYHA (New York Heart Association) Class III or IV heart failure. * Current use of medications significantly affecting metabolism of itraconazole (certain anti-convulsants, corticosteroids). See 3.5 Drug Interactions in protocol. * Current evidence of hyperthyroidism (which would increase metabolism of itraconazole). * Pregnant or lactating female or any female trying to get pregnant. * Claustrophobia that would interfere with MRI studies anticipated to last 45-50 minutes. * Metal implants deemed at risk for migration during MRI studies. * CrCl (Creatinine clearance) < 45 mL/min (increased risk of nephrogenic systemic fibrosis [NSF] from MRI Gadolinium contrast). * Known allergy to MRI contrast.

Study Objectives A trial to assess the pharmacokinetics and hepatic safety of EGCG in women with and without uterine fibroids. Conditions: Uterine Fibroids Intervention / Treatment: DIETARY_SUPPLEMENT: Epigallocatechin gallate (EGCG), DRUG: Clomiphene Citrate, DRUG: Letrozole Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: OTHER Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Healthy women >=18 to <=40 years of age with or without uterine fibroids * Must use a double-barrier method for contraception Exclusion Criteria: * Subjects using green tea/EGCG within 2 weeks prior to study enrollment * Known liver disease (defined as AST or ALT>2 times normal, or total bilirubin >2.5 mg/dL). * History of alcohol abuse (defined as >14 drinks/week) or binge drinking of >= 6 drinks at one time). * Subject using hormonal contraceptives * Subjects who are pregnant or breastfeeding * Known hypersensitivity to the study drugs * Any chronic disease

Study Objectives The goal of this clinical research study is to find out if Xeloda® (capecitabine) and radiation therapy can help to control breast cancer that did not respond well to chemotherapy. The safety of this study treatment will also be studied. Conditions: Breast Cancer Intervention / Treatment: RADIATION: Radiation Therapy, DRUG: Capecitabine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histological confirmation of invasive breast cancer * No contraindications to receiving a course of radiation treatment (pregnancy, prior radiation to the volume with disease, or systemic disease in which radiation therapy is an absolute contraindication) * Patients who have chemo-refractory gross disease in the breast causing symptoms (pain, drainage, duress) OR gross disease in the breast (greater than or equal to T3) and/or lymph node(s) progressive, persistent, or minimally responsive to chemotherapy deemed inoperable or questionable inoperable OR Recurrent gross disease in a previously unirradiated breast or on the chest wall or in the regional lymphatics (core biopsy will not be offered to patients without gross disease in the breast). * Are able to swallow and retain oral medication (intact pill) * Age over 18 * Female gender Exclusion Criteria: * Have an active or uncontrolled infection * Have dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent * Have used an investigational drug within 21 days preceding the first dose of study medication * Are receiving therapeutic anti-coagulation therapy (i.e. warfarin, heparin) * Uncontrolled arrhythmia or congestive heart failure (CHF) based on clinical history or physical exam * Patient cannot receive whole brain irradiation concurrently with Xeloda treatment.

Study Objectives To determine the percentage of patients and number of cycles in which a packed red blood cell transfusion was administered due to anemia and in which antibiotics were administered due to neutropenic fever. Conditions: Sarcoma Intervention / Treatment: DRUG: Aranesp (darbepoetin alfa), DRUG: Neulasta (pegfilgrastim), DRUG: Adriamycin, DRUG: Ifosfamide Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: PREVENTION Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with sarcoma which is locally advanced, at high risk for relapsed or metastatic for whom treatment with AI is indicated * Must be between 18-65 years of age * Women of childbearing potential should use effective contraceptive measures * Adequate hematologic, renal, and hepatic functions * Karnofsky performance status above or equal to 80 Exclusion Criteria: * Pregnant or lactating women. * Patients with comorbid condition which renders patients at high risk of treatment complication * Patients with metastatic disease to CNS * Patients with significant cardiac abnormalities * History of seizure disorder in the past 5 years * Patient has received any packed red blood cell transfusion within 2 weeks before study entry * Prior surgery or radiation therapy within 2 weeks of study entry * History of prior chemotherapy for sarcomas * Iron deficiency * Hypersensitivity to E.coli derived products

Study Objectives This is a phase 1 open label, 4 treatment, 4 sequence and 4 period crossover study in subjects with solid tumours no longer responding to, or eligible for standard therapies, and for whom there are no additional standard therapies likely to benefit the subject. Conditions: Malignant Solid Tumor Intervention / Treatment: DRUG: Olaparib Treatment A, DRUG: Olaparib Treatment B, DRUG: Olaparib Treatment C, DRUG: Olaparib Treatment D Location: Belgium Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * Provision of informed consent prior to any study specific procedures. * Female or male subject, aged > 18 years. * Histologically or, where appropriate, cytologically confirmed malignant solid tumour refractory or resistant to standard therapy for which no suitable effective standard therapy is available and in the opinion of the investigator might benefit from olaparib therapy. * Subjects must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below: * Haemoglobin >= 100 g/L with no blood transfusion in the past 28 days. * Absolute neutrophil count (ANC) >= 1.5 x 109/L. * Platelet count >= 100 x 109/L. * Total bilirubin <= 1.5 x institutional upper limit of normal (ULN). * Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) <= 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be <= 5x ULN. * Subjects must have creatinine clearance estimated of >=51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test: Estimated creatinine clearance =[(140-age [years]) x weight (kg) x 1.2] (x F)a serum creatinine (μmol/L) a where F=0.85 for females and F=1 for males * Eastern Cooperative Oncology Group (ECOG) performance status 0-1. * Subjects must have a life expectancy >= 16 weeks. * Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1. 8 Male subjects must use a condom during treatment and for 3 months after the last dose of olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male subjects should also use a highly effective form of contraception if they are of childbearing potential. 9 Subjects must have normal GI tract anatomy and function (see exclusion criteria for specifics). 10 Subjects is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations. Exclusion Criteria: * Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). * Previous randomisation in the present study. * Participation in another clinical study with an investigational product during the last 1 month. * Any previous treatment with a PARP inhibitor, including olaparib. * Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation > 500 ms, electrolyte disturbances, etc.) or subjects with congenital long QT syndrome. * Subjects receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment. * Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks. * Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents. * Persistent toxicities (Common Terminology Criteria for Adverse Event (CTCAE) > grade 2) caused by previous cancer therapy, excluding alopecia. * Subjects with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML. * Subjects with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The subject can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Subjects with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days * Major surgery within 2 weeks of starting study treatment and subjects must have recovered from any effects of any major surgery. * Subjects considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent. * Subjects unable to swallow orally administered medication and subjects with gastrointestinal disorders likely to interfere with absorption of the study medication including surgery on the upper GI tract and small bowel, malabsorptive disorders, inflammatory bowel disease, GI motility disorders, chronic diarrhea (more than 3 loose bowel movements per day) chronic constipation (no bowel movement for more than two days), recent (in last week) vomiting. * Pregnant or breastfeeding women. * Immunocompromised subjects, e.g., subjects who are known to be serologically positive for human immunodeficiency virus (HIV). * Subjects with a known hypersensitivity to olaparib or any of the excipients of the product. * Subjects with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids. * Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).

Study Objectives GVHD prophylaxis of sirolimus and mycophenolate mofetil for patients undergoing matched related allogeneic transplant for acute and chronic leukemia, MDS, high risk NHL and HL Conditions: Leukemia, Lymphoma, Non-Hodgkin, Hematologic Diseases, Acute GVHD Intervention / Treatment: DRUG: Sirolimus, DRUG: MMF, DRUG: BCNU, DRUG: VP-16, DRUG: CY, DRUG: FTBI, DRUG: BU Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Disease Categories: (one of the following) * AML, age 2 - 60 years beyond 2nd remission or relapsed/refractory disease * AML, age 51-60 years of age, in first or subsequent remission or relapsed/refractory disease * AML with multilineage dysplasia * ALL, age 2 - 60 years beyond 2nd remission or relapsed/refractory disease * ALL, age 51 - 60 years in first or subsequent remission or relapsed/refractory disease * CML Beyond 2nd chronic phase or in blast crisis * MDS; Includes World Health Organization classifications of refractory anemia with excess blasts-1 (RAEB-1), RAEB-2 and therapy-related MDS * Myeloproliferative disorders; MDS with poor long-term survival including myeloid metaplasia and myelofibrosis * High risk NHL in first remission * Relapsed or refractory NHL * HL beyond first remission * Males and females of any ethnic background 2 - 60 years of age * Karnofsky Performance Status >= 70% or Lansky performance status > 70% for patients < 16 years of age. * Matched related donor identified: 6/6 HLA-A, B and DRB1 * Willingness to take oral medications during the transplantation period * Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * Prior myeloablative allogeneic or autologous HCT * HIV infection * Pregnant * Lactating females * Evidence of uncontrolled active infection * Organ Dysfunction: * Serum creatinine > 1.5 mg/dL or 24 hour creatinine clearance < 50 ml/min * Direct bilirubin, ALT or AST > 2 x ULN * In adults DLCO < 60% predicted and in children room air oxygen saturation < 92% * In adults, left ventricular ejection fraction < 45% and in children, shortening fraction < 26% * Fasting Cholesterol > 300 mg/dL or Triglycerides > 300 mg/dL while on lipid-lowering agents. * Patients receiving investigational drugs unless cleared by the PI. * Patients with prior malignancies except basal cell carcinoma or treated carcinoma in-situ. * Cancer treated with curative intent > 5 years will be allowed. * Cancer treated with curative intent <= 5 years will not be allowed with PI approval.

Study Objectives The study is a phase I multicentre randomized, open, parallel-arm clinical trial conducted to investigate the IMP, namely 111In-CP04. The study consists of preclinical (to establish a clinically useful formulation for the radiolabelled peptide CP04), and a clinical step. The main objective of the clinical part of the project is to establish the safety of i.v. administration of a high peptide amount and to assess the tracer biodistribution and dosimetry in MTC and normal tissues and to determine critical organs as well as the evaluation of the potential of CCK2 receptor scintigraphy to detect cancer lesions for both low (10ug) and high (50ug) peptide amount and the decrease of kidney dose after co-administration of gelofusine /gelaspan as a nephroprotective agent. To achieve this, the following study design has been accepted: the first 4 patients will receive 2 peptide amount of CP04: low peptide amount (for diagnostic purpose) and high peptide amount (for therapeutic purpose) of CP04. If no SAE is present, the remaining pts will be randomized for 2 arms: high peptide amount of 111In-CP04 with and without gelofusine/gelaspan infusion. It is expected that CCK-2/gastrin receptor imaging will become a valid diagnostic method for a specific non-invasive staging and follow-up of patients with MTC, and treatment of recurrent and disseminated disease will be more efficient with minimized nephro- and myelotoxicity (if 111In labelled). Conditions: Medullary Thyroid Carcinoma Intervention / Treatment: DRUG: 111In-CP04, DRUG: 111In-CP04 with co-administration of gelofusine/gelaspan Location: Germany, Netherlands, Slovenia, Austria, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: SEQUENTIAL Masking: SINGLE

Inclusion Criteria: Related to the medullary cancer of the thyroid: * Histologically documented medullary cancer of the thyroid. * Presence of more than one distant or nodal, surgically untreatable metastases confirmed with either 18F-FDG PET/CT or enhanced-CT or MRI OR * Doubling time (DT) of serum calcitonin level less than two years prior to study entry and negative imaging. * Karnofsky performance status > 50%. * Life expectancy of more than 6 months. Related to the patient: * Male or female patients aged >18 years without upper age limit. * Ability to understand and willingness to sign a written informed consent document. * Written informed consent obtained according to international guidelines and local laws. Exclusion Criteria: Related to the MTC: * Patients with surgically treatable medullary thyroid cancer. * Patients with history of second malignancy other than basal cell carcinoma of the skin. Related to previous or concomitant therapies : * Participation in any other investigational trial within 3 months of study entry. * Previous external beam radiation therapy within two years. * Organ allograft requiring immunosuppressive therapy. Related to the patient: * Pregnancy, breast-feeding. * Known hypersensitivity to gastrin analogues. * Patients with concurrent illnesses that might preclude study completion or interfere with study results. * Patients with bladder outflow obstruction or unmanageable urinary incontinence. * Clinical diagnosis of disseminated intravascular coagulation. * Serum creatinine >170 μmol/L, GFR < 40 mL/min * Known history of hypersensitivity to gelofusine /gelaspan or any other contraindications to gelofusine/gelaspan infusion

Study Objectives The purpose of this study is to determine if Velcade (also known as bortezomib) can help prevent graft versus host disease (GVHD) developing after transplantation. This is done by using a combination of three immune suppressive medications: Velcade, tacrolimus and methotrexate. Stem cell transplantation is one of the options for patients with cancer of the blood or blood forming organs. Recently, allogeneic stem cell transplants have been performed using lower doses of chemotherapy and radiotherapy: non-myeloablative or "mini" transplants. GVHD is a significant problem that may occur even after "mini" transplantations. Information from other research studies, suggests that Velcade may help to reduce the risk of developing GVHD when given early after transplantation. Conditions: Hematologic Malignancies Intervention / Treatment: DRUG: Bortezomib (Velcade), DRUG: Tacrolimus, DRUG: Methotrexate, PROCEDURE: blood stem cell transplantation Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: PREVENTION Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with hematologic malignancies including myelodysplastic syndrome (MDS), who are at a high risk of complications after myeloablative transplantation * Patients have a donor (both related and unrelated) who are mismatched according to protocol criteria * 18 years of age or older * Performance status 0-2 * Life expectancy of > 100 days * Female subject is either post-menopausal or sterilized or willing to use an acceptable form of birth control * Male subject agrees to use an acceptable form of birth control Exclusion Criteria: * Evidence of HIV infection * Total bilirubin > 2.0mg/dl that is due to hepatocellular dysfunction * Aspartate aminotransferase (AST) > 90 * Known active hepatitis B or C * Serum creatinine > 2.0 * Greater than or equal to Grade 2 peripheral neuropathy within 21 days of enrollment * Prior allogeneic stem cell transplant * Patients with myeloproliferative disease (e.g. myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia) * Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV hear failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities * Hypersensitivity to Velcade, boron or mannitol * Pregnant or breast feeding * Patient has received other investigational drugs 14 days before enrollment * Serious medical or psychiatric illness * Another active solid tumor malignancy at the time of study entry

Study Objectives This study will explore the combination of the oral drug PF-00299804 and intravenous CP-751,871 in patients with advanced solid tumor. Each of these drugs have been given separately to patients in prior studies, and this study is to establish the safety and efficacy of the combination. Conditions: Carcinoma, Non-Small Cell, Neoplasm Metastasis Intervention / Treatment: DRUG: PF-00299804 Location: United States, Spain, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically documented advanced cancer, Eastern Cooperative Oncology Group (ECOG) 0-1; * Platelets > 100,000, ANC > 1500; * Ccr > 60 or serum creat. <1.5 * Non-small cell cancer cohort: * Eastern Cooperative Oncology Group (ECOG) 0-2, prior platin, < 4 prior chemotherapy regimen * HgA1C <5.7% Exclusion Criteria: * Active Central Nervous System (CNS) metastases; * prior IGF1-R targeted therapy * Any history of unstable angina, myocardial infarction or symptomatic congestive heart failure.

Study Objectives This phase II trial is studying how well cilengitide works in treating patients with prostate cancer. Cilengitide may stop the growth of prostate cancer by blocking blood flow to the tumor Conditions: Recurrent Prostate Cancer, Stage I Prostate Cancer, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer, Stage III Prostate Cancer Intervention / Treatment: DRUG: cilengitide 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: * A histologic or cytologic diagnosis of prostate cancer * No evidence of metastatic disease, or local progression * PSA-only progression despite androgen deprivation therapy and antiandrogen withdrawal (28 days for flutamide and 42 days for bicalutamide or nilutamide); PSA progression is defined as 3 consecutive rising levels, with an interval of > 1 week between each determination; the last determination must have a minimum value of >= 2 ng/ml and be determined within two weeks prior to registration * If the third confirmatory value is less than the previous value, the patient will still be eligible if a repeat value (No. 4) is found to be greater than the second value * Patients must continue on LHRH agonists; they also may continue on any stable doses (considered stable, if on current medicine dosing for one month or longer) of megace or corticosteroids; they must be off all other therapies intended to treat the cancer for 4 weeks * ECOG performance status of 0-2 * No prior EMD 121974 therapy is allowed * No investigational or commercial agents or therapies may be administered with the intent to treat the patient's malignancy * Testosterone < 50 ng/dl; patients must continue primary androgen deprivation with an LHRH agonist, if they have not undergone orchiectomy * Four weeks must have elapsed since major surgery * Life expectancy of greater than 6 months * Patients must have normal organ and marrow function as defined below obtained within 14 days prior to registration: * ANC >= 1,500/µl * Platelet count >= 100,000/ µl * Creatinine =< 1.5 x upper limits of normal * Bilirubin within normal limits * SGOT (AST) =< 2.5 x upper limits of normal * SGPT (ALT) =< 2.5 x upper limits of normal * PSA >= 2 ng/ml * The effects of EMD 121974 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because antiangiogenic agents are known to be teratogenic, men must agree to use adequate contraception prior to study entry and for the duration of study participation * Ability to understand and the willingness to sign a written informed consent that is approved by the Institutional Human Investigation Committee Exclusion Criteria: * Patients may continue on a daily Multi-Vitamin, but all other herbal, alternative and food supplements (i.e. PC-Spes, Saw Palmetto, St John Wort, etc.) must be discontinued before registration * Patients on stable doses of bisphosphonates which have been started no less than 6 weeks prior to protocol therapy, that show subsequent PSA progression, may continue on this medication, however patients are not allowed to initiate bisphosphonate therapy immediately prior or during 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 * Patients with a "currently active" second malignancy, other than non-melanoma skin cancers or superficial bladder cancer, are not eligible; patients are not considered to have a "currently active" malignancy if they have completed therapy and are now considered without evidence of disease for 2 years

Study Objectives To compare overall survival after receiving mitoxantrone and prednisone or docetaxel and prednisone in subjects with hormone-refractory metastatic prostate cancer. Conditions: Prostatic Neoplasms Intervention / Treatment: DRUG: Docetaxel, DRUG: Mitoxantrone, DRUG: Prednisone Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically or cytologically proven prostate adenocarcinoma * Androgen independent prostate Cancer S/P orchiectomy and/or LHRH agonist Testosterone < 50 ng/dl (ie 1.735 nmol/l) * Documented progressive disease * Patients should have achieved stable analgesia for 7 days * Karnofsky Performance Status >= 70 * No prior treatment with cytotoxic agent (except estramustine) * Normal cardiac function must be confirmed by Left ventricular ejection fraction * Adequate organ function: 1. Hematology: * Neutrophils > 1.5 x 10^9/L * Hemoglobin > 10 g/dl. Erythropoietin use is allowed, but red blood cell transfusion to upgrade the hemoglobin level is not allowed * Platelets > 100 x 10^9/L 2. Hepatic function: * Total bilirubin < the upper-normal limit of the institution. * Alanine aminotransferase and Aspartate transaminase < 1.5 times the upper-normal limit of the institution. 3. Renal function: * Creatinine < 1.5 times the upper normal limit (ie National Cancer Institution grade < 1) * No brain or leptomeningeal metastases Exclusion Criteria: * Prior radiotherapy to >25% of bone marrow (whole pelvic irradiation is not allowed) * prior cytotoxic chemotherapy, except monotherapy with estramustine * prior isotope therapy * history of another cancer within the preceding five year * symptomatic peripheral neuropathy grade >= 2 * other serious illness or medical condition: 1. Congestive heart failure even if controlled. Previous history of myocardial infarction or angina pectoris within 1 year from study entry, uncontrolled hypertension or uncontrolled arrhythmias. 2. Active uncontrolled infection 3. Peptic ulcer, unstable diabetes mellitus or other contraindications for the use of corticosteroids. 4. Auto-immune disease (lupus, sclerodermia, rheumatoid polyarthritis) * treatment with any other anti-cancer therapy * treatment with bisphosphonates The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Objectives The objective of this study is to describe the effect of optimized retreatment with bortezomib in combination with dexamethasone followed by prolonged therapy with bortezomib, versus standard retreatment with bortezomib in combination with dexamethasone on progression free survival (PFS). Conditions: Multiple Myeloma Intervention / Treatment: DRUG: bortezomib (optimized retreatment), DRUG: dexamethasone (optimized retreatment), DRUG: bortezomib (standard retreatment), DRUG: dexamethasone (standard retreatment) Location: Israel, Finland, Norway, Germany, Portugal, Turkey, Netherlands, Belgium, Sweden, France, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Have received a bortezomib containing regimen in one of the previous line(s) of therapy and have shown at least PR to the previous bortezomib therapy. * Have relapsed / progressed multiple myeloma following 1 or 2 previous lines of therapy as defined in the protocol. * Have measurable secretory multiple myeloma: measurable disease for secretory multiple myeloma is defined by at least one of the following measurements: serum M protein greater than or equal to 1 g/dL (>=10g/L], urine M-protein of >=200 mg/24 hours. * Have an ECOG performance status of <=2. * Have a life expectancy estimated at screening of >=6 months. Exclusion Criteria: * Has received more than 2 previous lines of therapy for multiple myeloma or has received no previous bortezomib-containing regimen. * Has been refractory to bortezomib, defined as either having progressed during bortezomib therapy or relapsed/progressed within 6 months after the last dose of bortezomib. * Has oligosecretory or nonsecretory multiple myeloma. * Has a history of a myocardial infarction within 6 months of enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. * Has peripheral neuropathy or neuropathic pain of grade 2 or greater intensity, as defined by the National Cancer Institute Common Terminology Criteria of Adverse Events (NCI CTCAE), version 4.0.

Study Objectives This is a Phase Ib/II experimental, open-label, dose escalation, active treatment study designed to determine the safety, tolerability, and recommended dose of the combination. During the Phase 2 portion of the study, we will assess progression-free survival (PFS), overall survival (OS),overall response rate (ORR), correlative endpoints, DNA methylation measured by microarray, and expression level of the genes as measured by microarray Conditions: Sarcoma Intervention / Treatment: DRUG: Docetaxel, DRUG: Gemcitabine, DRUG: Vorinostat, DRUG: Pegfilgrastim Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: * Patients must have histologically confirmed soft tissue sarcoma with evidence of metastatic or unresectable disease. * Patients must have measurable disease by RECIST 1.1. * Up to 32 prior cytotoxic chemotherapy regimens in the metastatic setting are allowed. Adjuvant chemotherapy or targeted therapy will not be considered a prior line of treatment. * Age >=18 years. * ECOG performance status <=2 (Karnofsky >=60%). * Life expectancy of greater than 12 weeks. * Patients must have normal organ and marrow function as defined below: * leukocytes >=3,000/µL * absolute neutrophil count >=1,500/µL * platelets >=100,000/µL * total bilirubin within normal institutional limits * AST(SGOT)/ALT(SGPT) <=1.5 X institutional upper limit of normal (ULN) * creatinine <=1.5 X institutional upper limit of normal (ULN) * Peripheral neuropathy, if present, should be <=grade 1. * Women of Child bearing potential MUST use contraceptives. * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * The following specific histologic subtypes of soft tissue sarcomas will be excluded: GIST, Kaposi's sarcoma, mesothelioma, dermatofibrosarcoma, chordoma, alveolar soft-part sarcoma. Also, all bone sarcomas are excluded including Ewing's sarcoma, osteosarcoma, GIST, low grade chondrosarcoma, and chordoma. * Patients who have had treatment with chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to starting study treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. * Patients who are receiving any other investigational agents. * Patients with known brain metastases. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine, docetaxel, vorinostat, or G-CSF. * Patients who have received and progressed on the combination of gemcitabine and docetaxel in the metastatic setting. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant and breastfeeding women * Patients taking concomitant HDAC inhibitors. * HIV-positive patients on combination antiretroviral treatment

Study Objectives This study is for patients with recently diagnosed blood cancer, called acute lymphoblastic leukemia (ALL). The standard treatment for this disease consists of many chemotherapy drugs that are given in different combinations in several steps. Each step of treatment is called a cycle. Patients will be treated with the chemotherapy drugs that are routinely used in ALL and which are given in multiple treatment cycles over several months. All the chemotherapy drugs that are used in this study have been approved by the Food and Drug Administration (FDA). One of the drugs, which is typically given to patients with ALL, is called Asparaginase. It is given together with the other drugs throughout the different cycles of treatment. This drug can be derived from several sources. The standard source is called E. coli Asparaginase, which is associated with a risk of allergic reactions. This drug stays in the body for a very short period of time; therefore, it has to be injected daily for 9-14 days in a cycle of treatment. In this study, a different form of Asparaginase will be used, called PEG-Asparaginase (also called Oncospar), which remains in the body for about two weeks, therefore, it can be given only once in a cycle of treatment and still maintains high blood levels of the drug. PEG-Asparaginase has recently been approved by the FDA to treat ALL. Most of the experience with the drug has been in children with ALL. In children it was found to be as safe as the standard form of Asparaginase and with less allergic reaction. It was also found to have the same effectiveness on ALL. The experience with this drug in adults has been more limited. The purpose of the study is to find out what side effects occur in adults when PEG-Asparaginase is given with other chemotherapy drugs and to see what effect it has on the response to treatment of ALL. Another purpose is to find out if the allergic reactions are reduced with PEG-Asparaginase. In children there is some early information that PEG-Asparaginase produces fewer antibodies than E.coli Asparaginase. Therefore, another purpose of the study is to see how many adult patients who receive PEG-Asparaginase develop antibodies against the drug. Conditions: Acute Lymphoblastic Leukemia Intervention / Treatment: DRUG: Daunorubicin, Vincristine, Prednisone, Methotrexate, PEG-Asparaginase, 6-Mercaptopurine, Cytoxan, Cytosine Arabinoside, VM-26 and 6-Thioguanine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with previously untreated ALL subtypes L1 and L2. * Patients with de novo Philadelphia (Ph)+ ALL (i.e. excluding those that are after blastic of CML) are eligible. However they will be referred to allogeneic hematopoietic stem cell transplantation and will continue on the study until they are ready to undergo the transplantation. At that time they will discontinue the study. Patients who are unable to undergo allogeneic transplantation will continue on the study. * Presence of 25% or more of lymphoblasts in the bone marrow by FAB criteria, confirmed by TdT positivity or by flow cytometry with standard ALL markers. * Patients may have received prior steroids. * Age: 18 - 55 years * Signed Informed Consent Exclusion Criteria: * Patients with Burkitt's ALL (L3 subtype) or CML lymphoblastic crisis are not eligible (including CML patients who present with ALL blastic crisis). * Psychological or emotional disorders which will make a valid informed consent impossible. * Bilirubin >1.5 mg/dl, creatinine > 2.5 mg/dl * Symptomatic congestive heart failure or unstable angina * Pregnant or lactating females * Known HIV positive status

Study Objectives The success of anti-CTLA4 therapy has inaugurated a paradigm shift in oncology where drugs target the immune system rather than cancer cells in order to stimulate the anti-tumor immune response. In situ immunization is a strategy where immunomodulatory products such as pathogens are injected into one tumor site in order to trigger a systemic anti-tumor immune response. Of importance, pre-clinical rationale has demonstrated that combination of anti-CTLA4 therapy together with intra-tumoral (IT) oncolytic virus can overcome primary resistance to systemic anti-CTLA4 therapy. Pexastimogene Devacirepvec (Pexa-Vec) is one of the new vaccinia oncolytic viruses genetically modified to express GM-CSF. This new and innovative oncolytic virotherapy should therefore synergize with anti-CTLA4 therapy via virus-induced tumor cell death \& tumor-antigen release, GM-CSF-induced recruitment/maturation/activation of antigen presenting cells, and anti-CTLA4-induced Treg blockade/depletion. Intra-tumoral delivery of immunostimulating agents should, therefore, provide lower toxicity of mAb targeting immune checkpoints. Of note, IT injections of GM-CSF-encoding oncolytic viruses have already been shown to induce immune-mediated tumor responses on local (injected) and distant (not injected) tumor sites. In solid injectable refractory/relapsing metastatic tumors, we make the hypothesis that the addition of Pexa-Vec to IT ipilimumab (anti-CTLA4 Ab) will overcome primary/secondary resistance to standard therapy and/or immunotherapy with a better in situ tumor antigen specific T-cell priming. Our proposal is to conduct a 2-part Phase I clinical trial in order to define the feasibility, the safety and the anti-tumor effects of intra-tumoral injections of ipilimumab in combination with the oncolytic virus Pexa-Vec. Dose escalation step will define the MTD and RP2D of that in situ immunization strategy. Expansion part will assess the anti-tumor effect of the combination. Conditions: Metastatic Tumor, Advanced Tumor Intervention / Treatment: BIOLOGICAL: Pexa-Vec, DRUG: Ipilimumab Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Male or female patients aged >= 18 years at time of inform consent signature * Histologically confirmed, advanced/metastatic solid tumor refractory or relapsing to/after standard therapy or the patient has refused or does not tolerate standard therapy. Any tumor types can be considered in Part A except hepatocellular carcinoma (HCC). In part B, tumor types may include melanoma, MSI-High colorectal carcinoma (CRC), head and neck tumors, gastric cancers, triple negative breast cancers and mesothelioma. * Tumor status (as determined by radiology evaluation): At least one injectable site >=2cm and <=8 cm in diameter and one distant non-injected measurable site (target site). NotaBene: for the DL5 and DL6, depending of the size of the injectable lesions, patients should present more than 1 injectable lesion (See Appendix 3). Of note, patients with only one injectable lesion with a diameter = 2 cm are not eligible for theses 2 DLs. * PS ECOG 0 or 1 * Minimal wash-out period for prior anti-cancer regimens (i.e. chemotherapy, immunotherapy, or radiation therapy) > 3 weeks before Week 1 day 1. * Resolution (i.e. <= Grade 1) of all toxicity related to prior anti-cancer treatment with exceptions of alopecia Grade 2, neuropathy Grade 2 and according to biological values presented in Criteria I8. * No major surgery within 4 weeks prior Week 1 day 1 * Laboratory requirements: 1. Absolute neutrophil count (ANC) >= 1 x 109/L 2. Lymphocytes >=1 x 109/L 3. Platelets >= 100 x 109/L; 4. Hemoglobin >= 90 g/L 5. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) <= 3 x ULN (if patient exhibits liver metastasis, up to 5 x ULN acceptable) and total bilirubin <= 3mg/dL 6. Serum creatinine <=1.5 x ULN or creatinine clearance is >=60 mL/min according to Cockcroft-Gault formula 7. International normalized ratio (INR) <=1.7 8. Serum chemistries within normal limits (high or low) or Grade 1 (with exception of sodium, potassium, glucose, calcium, upon Investigator discretion) * Life expectancy > 3 months * Negative pregnancy test for women of child-bearing potential within 72 hours before Week 1 Day 1 * Men and women of reproductive potential must be willing to double barrier methods of contraception during the treatment period and for up to 6 weeks after last Pexa Vec administration. * 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. * Patients must be covered by a medical insurance. Exclusion Criteria: * Known significant immunodeficiency due to underlying illness (e.g., HIV/AIDS) and/or immune-suppressive medication including systemic corticosteroids and/or blood CD4+ T-cells < 200/µL. * History of auto-immunity or untreated wounds from infection or inflammatory skin conditions. Ancient auto-immunity with stable endocrine oral substitution and vitiligo could be considered eligible by investigators. * Experience of a severe systemic reaction or side-effect as a result of a previous smallpox vaccination * Ongoing severe inflammatory skin condition (as determined by the investigator) requiring medical treatment * History of severe eczema (as determined by the investigator) requiring medical treatment * Severe or unstable cardiac disease, including significant coronary artery disease requiring angioplasty or stenting within the preceding 12 months, unless well-controlled and on stable medical therapy for at least 3 months * Medical conditions, per the investigator's judgment, that predispose the patient to untoward medical risk of tachycardia, or hypotension during or following treatment with Pexa-Vec * Previous treatment with Pexa-Vec or other vaccinia vector based treatment * Tumor tissue sample not available for biological studies (from the initial diagnosis and/or relapse) at time of inclusion * History of allergic reactions attributed to one of the compound of ipilimumab or compound of similar composition (as per Yervoy SPC® - see Appendix 5) * Hepatitis C virus therapy including interferon/pegylated interferon or ribavirin or by extension any other hepatitis C virus therapy that cannot be discontinued within 14 days prior to any Pexa Vec injection. Sponsor should be consulted if the patient is taking any other antiviral medications to determine eligibility and/or to determine wash-out duration. * Significant bleeding event within the last 12 months that places the patient at risk for IT injection procedure based on Investigator assessment * Anticoagulant or anti-platelet medication that cannot be interrupted prior to IT injections (as listed in the protocol). * Inability to suspend treatment with anti-hypertensive medication (including but not limited to: diuretics, beta-blockers, angiotensin converting enzyme [ACE] inhibitors, aldosterone antagonists, etc.) for 48 hours prior to and 48 hours after each Pexa Vec injection. * Prior malignancy except for the following: basal or squamous cell skin cancer, in situ cervical cancer, or other cancer adequately treated from which the patient has been disease-free for at least 3 years * Active brain metastasis (treated and stable brain metastasis accepted). * Any prior or planned organ transplant (e.g., liver transplant) or allogeneic hematopoietic stem cell transplantation. * Pregnant or breastfeeding women * Household contact exclusions for patients enrolled: Women who are pregnant or nursing an infant, Children < 1 year old, People with skin disease (e.g. eczema, atopic dermatitis and related diseases...), Immunocompromised hosts (severe deficiencies in cell-mediated immunity, including AIDS, organ transplant recipients, hematologic malignancies).

Study Objectives On March 17th, 2011, the European Commission issued a marketing authorization valid throughout the European Union for Eribulin mesylate (Halaven; Eisai Limited), for the treatment of patients with locally advanced or metastatic breast cancer who have progressed after at least two chemotherapic regimens for advanced disease. As the use of Eribulin will be widespread in this tumor setting, a better knowledge of its safety profile outside clinical trials is warranted. Indeed the possibility to select patients at risk for developing Eribulin-induced neuropathy, will allow the exclusion from these treatment of those patients harbouring the specific single nucleotide polymorphism (SNP). Given that Eribulin toxicity often results in treatment discontinuation, the ability to anticipate which patients will experience severe toxicity could allow for either early intervention or even possibly for prophylactic therapy, or for selection of the patients to be treated. Conditions: Metastatic Breast Cancer, Toxicity, Neurotoxicity, Drug Toxicity, Adverse Drug Event Intervention / Treatment: DRUG: ERIBULIN MESYLATE Location: Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: HEALTH_SERVICES_RESEARCH Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Diagnosis of metastatic breast cancer * Previous treatment with anthracyclines and taxanes * Patients who will start Eribulin or who have already received only the first dose (cycle 1, day 1) of Eribulin according to the approved indication * Ability to comply with sample collection * Patient has signed the study Informed Consent Form (ICF) and the specific Pharmacogenetic ICF. * Absence of any contraindication to treatment Exclusion Criteria: * Previous treatment with Eribulin in a previous line of treatment * Previous treatment with Eribulin off label

Study Objectives This research is being done because we do not know the best treatment for advanced Squamous Cell Carcinoma of the Head and Neck. These cancers have been treated with a combination of surgery, radiation and chemotherapy in varying combination. When the tumor is inoperable, radiation therapy is used with or without chemotherapy in the hope of curing the tumor. Recently, it has become recognized as generalized knowledge that cancer cells are hypoxic (low oxygen concentration). Because of the low oxygen concentrations, many cancer treatments have not been successful. The theory behind this study is to give oxygen to patients prior to chemotherapy and radiation in hopes of generating greater results in killing cancer cells. The purpose of this study has two main objectives. The primary objective is to determine patient tolerance to each arm of the trial. The second objective is to determine the feasibility of treatment delivery and acute toxicities associated with each regimen. It is our intention to undertake a randomized and controlled trial should this Phase I trial prove successful in terms of patient tolerance. Conditions: Carcinoma, Squamous Cell, Cancer of the Head and Neck Intervention / Treatment: DRUG: Hyperbaric Oxygen Therapy, DRUG: Hyperbaric Oxygen, DRUG: Hyperbaric oxygen, DRUG: Hyperbaric oxygen 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 with histological proof (from the primary lesion and/or lymph nodes) of squamous cell carcinoma of the oral cavity, oropharynx, or hypopharynx. * Patients should have Stage III or IV disease, M0 * Patients must have life expectancy of at least 6 months and a Karnofsky performance status of >= 70 * Age >= 18 years and <= 70 years * No distant metastatic disease * No clinically significant heart disease: * No significant ventricular arrhythmia requiring medication with antiarrhythmics * No symptomatic coronary artery disease (angina) * No myocardial infarction within the last 6 months * No second or third degree heart block or bundle branch block or clinically significant conduction system abnormality * Patients must sign a study-specific informed consent form Exclusion Criteria: * Histology other than squamous cell carcinoma * Evidence of metastasis (below the clavicle or distant) by clinical or radiographic means * Prior complete resection of the primary tumor * Prior chemotherapy (Bleomycin) for head and neck cancer or radiotherapy to the head and neck * Patients with simultaneous primaries * Pregnancy * Pulmonary pathologies (risk of decompression-induced pulmonary barotrauma): * Current, untreated pneumothorax * Previous history of pneumothorax * Previous history of intrathoracic surgery * History of pulmonary blebs or bullous lung disease * Associated with CO2 retention * Poorly controlled or associated with acute bronchospasm * Where the hyperbaric physician deems the patient to have an unacceptable risk for hyperbaric treatments * Claustrophobia

Study Objectives Patients with non-surgical or renal cell carcinoma that has spread who are starting treatment for the first time with Yervoy and Opdivo in the real world Conditions: Renal Cell Carcinoma, Kidney Cancer Intervention / Treatment: OTHER: Non-Interventional Location: Japan Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Patients with unresectable or metastatic renal cell carcinoma who are initiating treatment for the first time with Yervoy and Opdivo in accordance with the Japanese package insert will be included in this PMS Exclusion Criteria: * Patients receiving combination therapy with Yervoy and Opdivo for non RCC indication will be excluded from this PMS Other protocol defined inclusion/exclusion criteria could apply

Study Objectives Dutasteride inhibits the conversion of testosterone to dihydrotestosterone (DHT) the male hormone that leads to benign prostate growth. By blocking the conversion of testosterone to DHT, dutasteride could allow bicalutamide to be a more effective anti-androgen thus prolonging bicalutamide's efficacy. Conditions: Neoplasms, Prostate Intervention / Treatment: DRUG: dutasteride, DRUG: placebo, DRUG: bicalutamide Location: United States, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion criteria: * Men >=40 and <=90 years of age * Must have asymptomatic prostate cancer that has progressed during androgen deprivation therapy (rising PSA). PSA progression must have occurred after first-line treatment with GnRH analogues ( e.g. leuprolide, goserelin) or orchiectomy. PSA progression is defined by three rises in PSA each measured at least 4 weeks apart within the previous year. * Serum PSA >=2 and <=20ng/ml from central laboratory. One PSA retest from central laboratory is allowed if the value is <2 or >20ng/ml; or if the PSA value is not consistent with the previous rising PSA values that determined progression while on a GnRH analogue. * Serum Testosterone <50ng/ml from central laboratory. * Non-metastatic prostate cancer as confirmed on prior bone scan performed within 8 weeks of screening. * Expected survival >= 2 years * ECOG Performance status 0, 1, or 2 Exclusion criteria: * Additional hormonal therapy (excluding the current use of a GnRH analogue) within the past 6 months of: * Estrogens (e.g. megestrol, medroxyprogesterone, cyproterone, DES) * Drugs with antiandrogenic properties (e.g., spironolactone if >50mg/day, flutamide, bicalutamide*, ketoconazole**, progestational agents) *The use of an antiandrogen during GnRH analogue induction for <6 weeks is acceptable, but none within the 3 months prior to study entry. **The use of topical ketoconazole is permitted prior to and during the study. NOTE: Use of dietary and herbal supplements (e.g., selenium, Vitamin E, saw palmetto), excluding daily vitamins, during the study is discouraged, but not prohibited. All dietary and herbal supplement usage will be recorded in the eCRF. * Treatment with oral glucocorticoids during the 3 months prior to randomization or expectation of their use during the study. * Prior chemotherapy for prostate cancer. (prior prostatectomy or radiotherapy to the prostate are allowed) * Prostate surgery including TUNA, TURP, TUIP, laser treatment, thermotherapy, balloon dilatation, prosthesis, and cryosurgical ablation within 2 months prior to enrollment. * Current and/or previous use of the following medications: * Finasteride (Proscar, Propecia), or Dutasteride (GI198745, AVODART) exposure within 6 months prior to study entry * Anabolic steroids (within 6 months prior to study entry) * Participation in any investigational or marketed drug trial within the 30 days prior to the first dose of study drug or anytime during the study period. * Any unstable serious co-existing medical condition(s) including but not limited to myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident within 6 months prior to Screening visit; uncontrolled diabetes; or peptic ulcer disease which is uncontrolled by medical management. * Abnormal liver function test greater than 1.5 times the upper limit of normal for alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP] or bilirubin. * Serum creatinine >2.0 times the upper limit of normal. * History of another malignancy within five years that could affect the treatment of prostate cancer or survival of the subject. * History or current evidence of drug or alcohol abuse within the last 12 months. * History of any illness (including psychiatric) that, in the opinion of the investigator, might confound the results of the study or pose additional risk to the subject. * Known hypersensitivity to any 5 alpha-reductase inhibitor or to any drug chemically related to dutasteride.

Study Objectives Patients with extensive and bulky disease are often those whose initial surgery is delayed after 3 or 4 cycles of neo-adjuvant chemotherapy. In that case, there is, indeed, some concern to administer bevacizumab during the chemotherapy surrounding the interval debulking surgery due to the long half life (14- 21 days) of this monoclonal antibody and the interference of anti angiogenic agents with wound healing. Vargatef® (Nintedanib) might offer a better alternative to bevacizumab in the neo-adjuvant setting. Vargatef® (Nintedanib) has a much shorter half-life of 7 to 19 hours. Preliminary experience in cancer did not show a trend for increased incidence of fistula or bowel perforation. For more details please refer to the investigator drug brochure for Vargatef® (Nintedanib). This trial will compare progression-free survival and surgical complications of 188 patients with FIGO stage IIIC/IV treated in first line with either neo-adjuvant chemotherapy (carboplatin \& paclitaxel) and interval debulking surgery or the same treatment + Vargatef® (Nintedanib). Conditions: Ovarian Cancer Intervention / Treatment: DRUG: vargatef, DRUG: placebo Location: France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * First diagnosis of histological confirmed (cytology alone excluded) epithelial ovarian cancer, fallopian tube or primary peritoneal cancer. Histology should be obtained by laparoscopy (or by laparotomy), * FIGO-Stages IIIC - IV, * ECOG performance status < 2, * Life expectancy of at least 6 months, * Primary debulking surgery denied and maximum surgical effort of cytoreduction with the goal of no residual disease planned as interval debulking surgery, * Interval between diagnosis and enrolment (informed consent) <= 8 weeks, * Adequate hepatic, renal and bone marrow functions: Platelets > 100 000 /μL, Hemoglobin > 9.0 g/dL, Absolute Neutrophil Count (ANC) > 1500/μL, Prothrombin time and/or partial thromboplastin time < 50% deviation from normal limits in the absence of therapeutic anticoagulation, Proteinuria < CTCAE grade 2, Total bilirubin <= upper limit of normal (ULN), ALT and/or AST <= 2.5 x ULN, Glomerular filtration rate >40 mL/min, * Females, age >= 18 years, * Patient has given written informed consent, Exclusion Criteria: * Histological diagnosis of malignant tumour of non-epithelial origin (e.g. germ cell tumour, malignant mixed mullerian tumour, sex cord-stromal tumour) of the ovary, the fallopian tube or peritoneum or borderline tumour of the ovary (tumour of low malignant potential), * Non-healing wound, ulcer (intestinal tract, skin) or bone fracture, * Clinical symptoms or signs of gastrointestinal obstruction, * History of major thromboembolic event, defined as: * Pulmonary embolism (PE) within 6 months prior to enrolment, * Recurrent pulmonary embolism (history of at least 2 events), * History of at least 2 unprovoked (without a transient or reversible risk factor) events of proximal deep venous thrombosis, * Prior thrombosis or thromboembolic event in the presence of an inherited coagulopathy (including deficiency of antithrombin, deficiency of protein C or protein S, Factor V Leiden mutation, Prothrombin G20210A mutation), * Patients with perioperative thrombosis including proximal deep vein thrombosis (DVT) or thrombosis of visceral vessels not associated with pulmonary embolism may be included in the trial if stable therapeutic anticoagulation is documented, * Known inherited or acquired bleeding disorder, * Significant cardiovascular diseases, including: * Hypertension not controlled by medical therapy, * Unstable angina within the past 6 months, * History of myocardial infarction within the past 6 months, * Congestive heart failure > NYHA II, * Clinically relevant cardiac arrhythmia * Peripheral vascular disease Fontaine stage >=3, * Clinically relevant pericardial effusion (e.g. pericardial effusion with echocardiographic or clinical signs of haemodynamic impairment), * History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 6 months, * Serious infections in particular if requiring systemic antibiotic (antimicrobial, antifungal) or antiviral therapy, including HIV-infection, hepatitis B and/or C infection, * Poorly controlled diabetes mellitus or other contraindication to high dose corticosteroid therapy, * Clinical symptoms of brain metastases and/or diagnosis of brain metastases on imaging, * Pre-existing sensory or motor neuropathy CTCAE >= 2, except due to trauma, * Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug, * Other malignancy diagnosed within the past 5 years, except: * non-melanomatous skin cancer (if adequately treated), * cervical carcinoma in situ (if adequately treated), * carcinoma in situ of the breast (if adequately treated), * prior or synchronous endometrial cancer (if adequately treated), provided the following criteria are met: * Disease stage FIGO <= IB, * No more than superficial myometrial invasion, * Not poorly differentiated (less than grade 3, no papillary serous or clear cell histology), * Prior systemic therapy for ovarian cancer (e.g. chemotherapy, monoclonal antibody therapy, oral targeted therapy, hormonal therapy), * Prior radiotherapy to the abdomen or prior radiotherapy to an extra-abdominal target volume that would bear the risk of increased toxicity of chemotherapy, * Hypersensitivity to Vargatef® (Nintedanib) and/or the excipients of the trial drugs, * Serious illness or concomitant non-oncological disease such as neurologic, psychiatric or infectious disease, active ulcers (gastrointestinal tract, skin) or a 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, * Patients with preserved reproductive capacity who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner) during the trial and for at least twelve months after end of active therapy, * 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, * Any contraindications for therapy with paclitaxel or carboplatin, e.g. a history of severe hypersensitivity reactions to paclitaxel or platinum-containing compounds and their excipients, or other drugs formulated with Polyoxyl 35 Castor Oil - ELP, * Treatment with other investigational drugs or participation in another clinical trial testing a drug within the past four weeks before start of therapy or concomitantly with this trial.

Study Objectives The purpose of this study is to determine the safety and effectiveness of different dose regimens of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). Conditions: Relapsed or Refractory Chronic Lymphocytic Leukemia Intervention / Treatment: DRUG: lenalidomide Location: Germany, Canada, Italy, Spain, United Kingdom, United States, Sweden, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Age >= 18 years at the time of signing the informed consent form * Must be able to adhere to the study visit schedule and other protocol requirements * Must have a documented diagnosis of B-cell CLL * Must be relapsed or refractory to at least 1 regimen for treatment of CLL. At least one of the prior treatments must have included a purine analog-based or bendamustine-based regimen * Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of <= 2. Exclusion Criteria: * Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form * Active infections requiring systemic antibiotics * Systemic treatment for B-cell CLL within 28 days of initiation of lenalidomide treatment * Alemtuzumab therapy within 120 days of initiating lenalidomide treatment * Prior therapy with lenalidomide * History of grade 4 rash due to prior thalidomide treatment * Planned autologous or allogeneic bone marrow transplantation * Central nervous system (CNS) involvement as documented by spinal fluid cytology or imaging. * Uncontrolled hyperthyroidism or hypothyroidism * Venous thromboembolism within 12 months * >= Grade 2 neuropathy * Uncontrolled autoimmune hemolytic anemia or thrombocytopenia * Disease transformation [i.e. Richter's Syndrome (lymphomas) or prolymphocytic leukemia] * Participation in any clinical study or having taken any investigational therapy within 28 days prior to initiating lenalidomide therapy

Study Objectives This phase I trial is studying the side effects and best dose of AZD2171 in treating young patients with recurrent, progressive, or refractory primary CNS tumors. AZD2171 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. Conditions: Childhood Atypical Teratoid/Rhabdoid Tumor, Childhood Central Nervous System Germ Cell Tumor, Childhood Cerebral Anaplastic Astrocytoma, Childhood Cerebral Astrocytoma, Childhood Grade I Meningioma, Childhood Grade II Meningioma, Childhood Grade III Meningioma, Childhood Infratentorial Ependymoma, Childhood Oligodendroglioma, Childhood Spinal Cord Neoplasm, Childhood Supratentorial Ependymoma, Recurrent Childhood Brain Neoplasm, Recurrent Childhood Brain Stem Glioma, Recurrent Childhood Cerebellar Astrocytoma, Recurrent Childhood Cerebral Astrocytoma, Recurrent Childhood Ependymoma, Recurrent Childhood Medulloblastoma, Recurrent Childhood Pineoblastoma, Recurrent Childhood Subependymal Giant Cell Astrocytoma, Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor, Recurrent Childhood Visual Pathway Glioma Intervention / Treatment: DRUG: Cediranib Maleate 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 primary CNS tumor * Histologically benign brain tumors (e.g., low-grade glioma) allowed * Histological requirement waived for intrinsic brain stem or diffuse optic pathway tumors, but must have clinical and/or radiographic evidence of progression * Recurrent, progressive, or refractory disease * Absolute neutrophil count >= 1,000/mm^3 (unsupported) * Platelet count >= 75,000/mm^3 (unsupported) * Creatinine =< 1.5 times upper limit of normal (ULN) OR glomerular filtration rate >= 70 mL/min * Bilirubin =< 1.5 times ULN * ALT =< 2.5 times ULN * Urine dipstick or urinalysis < 1+ protein * Albumin >= 3 g/dL * Karnofsky performance status (PS) 60-100% (> 16 years of age) OR Lansky PS 60-100% (=< 16 years of age) * Karnofsky/Lansky PS 70-100% for patients at increased risk for compromised LVEF * Hemoglobin >= 8 g/dL (transfusion support allowed) * No overt renal, hepatic, cardiac, or pulmonary disease * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * QTc prolongation =< 500 msec * No other significant ECG abnormality within the past 14 days * No clinically significant, unrelated, systemic illness, including serious infections or significant cardiac, pulmonary, hepatic, or other organ dysfunction, that would preclude study participation * No uncontrolled hypertension * Defined as systolic and diastolic BP > 95th percentile for age (ages 1-17) * Defined as BP > 140/90 (ages 18 and older) * No New York Heart Association class III or IV disease and Karnofsky/Lansky PS < 70 * Class II disease controlled with treatment and increased monitoring is allowed * Recovered from all prior therapy * No prior AZD2171 * At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for nitrosoureas) * More than 1 weeks since prior investigational or biologic agents * If the investigational or biologic agent has a prolonged half-life (> 48 hours), then these patients must be discussed with the study chair prior to registration * No concurrent drugs or biologics with proarrhythmic potential * More than 3 months since last fraction of craniospinal radiotherapy or total-body irradiation * More than 4 weeks since last fraction of focal irradiation to symptomatic metastatic sites * At least 6 months since prior allogeneic bone marrow transplantation * At least 3 months since prior autologous bone marrow or stem cell transplantation * At least 1 week since prior filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa (2 weeks for pegfilgrastim) * No other concurrent investigational agents * Concurrent dexamethasone allowed provided patient is on a stable or decreasing dose for >= 1 week before study entry * No concurrent chemotherapy * No concurrent routine use of G-CSF, GM-CSF, or epoetin alfa * Able to swallow tablets * Any neurologic deficits must be stable for >= 1 week * If the investigational or biologic agent has a prolonged half-life (> 48 hours), then these patients must be discussed with the study chair prior to registration Exclusion Criteria: * No known curative therapy available

Study Objectives This is an open-label, randomized trial in relapsed refractory subjects with mantle cell lymphoma (MCL). Conditions: Lymphoma Intervention / Treatment: DRUG: Temsirolimus (CCI-779), DRUG: Temsirolimus (CCI-779), DRUG: Investigator's choice Location: Chile, Canada, Germany, Italy, Brazil, Netherlands, Spain, Switzerland, United States, Belgium, Australia, United Kingdom, Austria, China, Argentina, Sweden, France, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Mantle cell lymphoma (MCL) confirmed with histology, immunophenotype, and cyclin D1 analysis * Received 2 to 7 prior therapies which may include hematopoietic stem cell transplant (i.e. induction + consolidation + maintenance) * Prior treatment with an alkylating agent and an anthracycline, rituximab, individually or in combination, and status that is at least one of the following: * Primary disease refractory to at least 2 regimens; * Refractory to at least 1 regimen after first relapse; * Refractory or untreated after second or greater relapse; * Refractory to first line and relapsed after second line. Chemotherapy combinations may include, but are not limited to: CHOP (Cyclophosphamide, doxorubicin, vincristine, prednisone), R-CHOP (Rituximab, Cyclophosphamide, doxorubicin, vincristine, prednisone), FCM (Fludarabine, cyclophosphamide, mitoxantrone), R-FCM (Rituximab,Fludarabine, cyclophosphamide, mitoxantrone), ICE(Ifosfamide, carboplatin, etoposide), DHAP (Dexamethasone, cisplatin, cytarabine) and hyper-CVAD (Cyclophosphamide, doxorubicin, vincristine, dexamethasone). Exclusion Criteria: * Subjects who are less than or equal to six month from allogeneic hematopoietic stem cell transplant and who are on immunosuppressive therapy or have evidence of graft versus host disease * Prior investigational therapy within 3 weeks of first dose. Investigational therapy is defined as treatment that is not approved for any indication. * Active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, requirement for corticosteroids and/or progressive growth. (Treated CNS metastases must be stable for > 2 weeks prior to Day 1.)

Study Objectives Brain tumors are the leading cause of death from solid tumors in children. Tumor imaging is important in the management of these tumors, but current imaging methods have limitations in providing the necessary information for optimal treatment of these patients. The goal of this study is to evaluate the potential utility of positron emission tomography (PET) with 3'-deoxy-3'-\[F-18\] fluorothymidine (18F-FLT) in the medical management of brain tumors in children. Funding source - FDA Office of Orphan Product Development (OOPD) Conditions: Brain Neoplasms Intervention / Treatment: DRUG: [18F] FLT Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: DIAGNOSTIC Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * age 21 years or less * capable of achieving imaging without need for sedation or anesthesia (typically age 8 years or greater, but there is no lower limit for age for eligibility) * Karnofsky Performance Status of 50 or greater in subjects age 12 years or greater, for age less than 12 years a Lansky play scale of 50% or greater * Patients receiving steroids and/or anti-seizure medications are eligible Exclusion Criteria: * clinically active infection * pregnancy or breast-feeding * serious intercurrent medical illness * require emergency surgical intervention that would be inappropriately delayed by FLT-PET imaging

Study Objectives The investigators do the clinical trial (patients with metastatic colorectal cancer treated with donafenib/placebo after failure of standard therapy) to assess efficacy and safety of donafenib in patients with metastatic colorectal cancer, progressing after all approved standard therapies. Conditions: Metastatic Colorectal Cancer Intervention / Treatment: DRUG: Donafenib, DRUG: Placebo Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Histological or cytological documentation of adenocarcinoma of the colon or rectum; * Subjects with metastatic colorectal cancer and must have progressed during or within 3 months following the last administration of approved standard therapies which must include a fluoropyrimidine, oxaliplatin and irinotecan: 1. Subjects treated with oxaliplatin in an adjuvant setting should have progressed during or within 6 months of completion of adjuvant therapy; 2. Subjects who progress more than 6 months after completion of oxaliplatin containing adjuvant treatment must be retreated with oxaliplatin-based therapy to be eligible; 3. Subjects who have withdrawn from standard treatment due to unacceptable toxicity warranting discontinuation of treatment and precluding retreatment with the same agent prior to progression of disease will also be allowed into the study; 4. Subjects may have received prior treatment with bevacizumab and/or cetuximab/panitumumab. * 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 (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)]. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 1; * Life expectancy of at least 3 months; * Adequate bone marrow, liver and renal function as assessed by the laboratory required by protocol conducted within 7 days before randomization (platelets >80× 109/L, neutrophil > 1.5 × 109/L, Hb>=85g/L, serum creatinine <= 1.5×ULN, total bilirubin <= 1.5×ULN, and serum transaminase<=2.5×ULN or <=5.0ULN if liver involvement); Exclusion Criteria: * Prior treatment with TKIs. * 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 (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)]. * Subjects who have no evaluable lesion except Pleural effusion, ascites or bone metastases lesion; * Major surgery have been completed within 4 weeks before the first dose of study medicine. * Subjects who have open wounds, active ulcers or plural stomata; * Subjects who have completed radiotherapy or systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and hormonal therapy during this trial or within 4 weeks before the first dose of study medicine; * Cardiological disease including Congestive heart failure, Unstable angina, Myocardial infarction, Cardiac arrhythmias requiring anti-arrhythmic therapy. * Pleural effusion or ascites that causes respiratory compromise. * Arterial or venous thrombotic or embolic events. * Any history of or currently known brain metastases.

Study Objectives The purpose of this study is to: Find out how safe and effective (by monitoring the good and/or bad effects) treatment with high dose temozolomide, thiotepa and carboplatin with stem cell rescue followed by 13-cis-retinoic acid has on children and adolescents with recurrent/refractory brain tumors Find out how the body uses 13-cis-retinoic acid by studying the your blood levels and proteins in the blood that break down the 13-cis-retinoic acid Determine how well 13-cis-retinoic acid penetrates into the spinal fluid. Conditions: Brain Tumors Intervention / Treatment: DRUG: temozolomide, thiotepa, carboplatin, 13-cis-retinoic acid Location: United States, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with recurrent or refractory medulloblastoma/PNET, CNS germ cell tumors, ependymomas, AT/RT, high grade glioma and other malignant brain tumors. Brainstem gliomas are eligible if residual disease is < 1.5cc and if the patient is off decadron. * Patients must have recurrent or refractory disease following at least one prior course of therapy and must have minimal residual disease defined as < 1.5 cm2 of enhancement. Patients with + CSF cytology, linear or fine nodular leptomeningeal disease are eligible. * Adequate hematologic, renal, liver, and cardiac function as demonstrated by laboratory values performed within 21 days, inclusive, prior to administration of temozolomide. * Patients must have an adequate number of autologous stem cells available defined as a minimum of 2 x 106 CD 34+ cells/kg and preferably at least 5 x 106 CD 34+ cells/kg. Exclusion Criteria: * Previous myeloablative therapy * Frequent vomiting or medical condition that could interfere with oral medication intake (e.g., partial bowel obstruction) * Previous or concurrent malignancies at other sites with the exception of surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin. Patients with prior malignancies which have not required anti-tumor treatment within the preceding 24 months are eligible.

Study Objectives This phase I trial studies the side effects and best dose of tipifarnib in treating patients with myelodysplastic syndromes. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Conditions: Chronic Myelomonocytic Leukemia, de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Refractory Anemia, Refractory Anemia With Excess Blasts, Refractory Anemia With Excess Blasts in Transformation, Refractory Anemia With Ringed Sideroblasts, Refractory Cytopenia With Multilineage Dysplasia Intervention / Treatment: DRUG: tipifarnib, 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 histologically MDS (including French-American-British [FAB] types refractory anemia [RA], refractory anemia with ringed sideroblasts [RARS], refractory anemia with excess blasts [RAEB], refractory anemia with excess blasts in transformation [RAEBT], or chronic myelomonocytic leukemia [CMMoL]); for the purpose of the study, all patients will be classified by World Health Organization (WHO) criteria * By these criteria, FAB RA are split into: * Pure dyserythropoietic refractory anemia (PRA) * Refractory cytopenia with multilineage dysplasia (RCMD) * FAB RARS is split into: * Pure sideroblastic anemia (PSA) * Refractory sideroblastic cytopenia with multilineage dysplasia (RSCMD) * FAB RAEB is split into: * RAEB I (< 10% BM blasts) * RAEB II (10-20% BM blasts) * Patients with CMMoL, and RAEBT by FAB classification will be included in the protocol * Prognosis will be assessed by International Prognostic Scoring System (IPSS) criteria * =< 2 prior therapies * Eastern Cooperative Oncology Group (ECOG) performance status =< 2 * Life expectancy of greater than 12 weeks * Bilirubin =< 1.5mg % * Creatinine =< 1.5mg % * Women of child-bearing 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 or suspect she is pregnant while participating in this study, she should inform her treating physician immediately * Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * Patients who have had chemotherapy or radiotherapy within 4 weeks (3 months for UCN01) 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 * History of allergic reactions attributed to compounds of similar chemical or biologic composition to R115777 (such as imidazoles) * Patients eligible for bone marrow transplant (=< 60 years old), with a compatible sibling, no contraindications for transplant * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with R115777. * Growth factors other than filgrastim (G-CSF) are excluded; patients should be off excluded growth factors for 2 weeks

Study Objectives The goal of this research is to test if the conditioning regimen, fludarabine and total body irradiation (FluTBI), can lead to a safer and more effective stem cell transplant treatment regimen for ALL patients older than 40 years of age and/or younger patients with high risk medical conditions. The primary objective is to establish the efficacy of allo HCT in older ALL patients using myeloablative FluTBI conditioning regimen. The investigators are also assessing the safety and toxicity of allo HCT in older ALL patients using myeloablative FluTBI conditioning regimen. Conditions: Adult Lymphoblastic Lymphoma Intervention / Treatment: DRUG: Fludarabine, PROCEDURE: Total Body Irradiation 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: * Disease Criteria: * ALL in complete remission (CR) at the time of transplant. Remission is defined as "less than 5.0% bone marrow lymphoblasts by morphology," as determined by a bone marrow aspirate obtained within 2 weeks of study registration. * Philadelphia chromosome positive ALL is allowed. * Lymphoid blastic crisis of CML will be included (provided that patients achieve CR). * Age Criteria: Equal or above age 40 and up to 65 years. If younger than 40, there must be comorbidities which preclude the patient to undergo CyTBI conditioning regimen. * Organ Function Criteria: All organ function testing should be done within 28 days of study registration. * Cardiac: Left ventricular ejection fraction (LVEF) >= 50% by MUGA (Multi Gated Acquisition) scan or echocardiogram. * Pulmonary: FEV1 (Forced expiratory volume in 1 second) and FVC (Forced vital capacity) >= 50% predicted, DLCO (alveolar diffusion capacity for carbon monoxide) (corrected for hemoglobin) >= 50% of predicted. * Renal: The estimated creatinine clearance (CrCl) must be equal or greater than 60 mL/min/1.73 m2 as calculated by the Cockcroft-Gault Formula: CrCl = (140-age) x weight (kg) x 0.85 (if female)/72 x serum creatinine (mg/dL). * Hepatic: * Serum bilirubin 2.0 g/dL * Aspartate transaminase (AST)/alanine transaminase (ALT) 2.5 ULN * Alkaline phosphatase 2.5 ULN * Performance status: Karnofsky >= 70% * Consent: Patient must be informed of the investigational nature of this study in accordance with institutional and federal guidelines and have the ability to provide written informed consent prior to initiation of any study-related procedures, and ability,in the opinion of the principal investigator, to comply with all the requirements of the study. * Presence of a willing adult HLA-matched sibling (excluding identical twin) or HLA-matched unrelated donor meeting all the criteria for routine allo HSCT. All donors will be evaluated for eligibility and suitability per the standard of care according to the FACT and NMDP guidelines. Exclusion Criteria: * Non-compliant to medications. * No appropriate caregivers identified. * HIV1 (Human Immunodeficiency Virus-1) or HIV2 positive * Active life-threatening cancer requiring treatment other than ALL * Uncontrolled medical or psychiatric disorders. * Uncontrolled infections, defined as positive blood cultures within 72 hours of study entry, or evidence of progressive infection by imaging studies such as chest CT scan within 14 days of registration. * Active central nervous system (CNS) leukemia * Preceding allogeneic HSCT * Receiving intensive chemotherapy within 21 days of registration. Maintenance type of chemotherapy will be allowed.

Study Objectives This is a single-arm, open-label, multicentre phase II study evaluating the safety and efficacy of the combination of the G.O.N.O. FOLFOXIRI regimen with bevacizumab as first-line treatment of metastatic colorectal cancer. Conditions: Colorectal Cancer Metastatic Intervention / Treatment: DRUG: Bevacizumab, DRUG: Irinotecan, DRUG: Oxaliplatin, DRUG: 5-fluorouracil/leucovorin Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed colorectal adenocarcinoma * Unresectable and measurable metastatic disease (RECIST criteria) * Male or female, aged > 18 years and <= 75 years * ECOG Performance Status (PS) < 2 if aged < 71 years * ECOG PS = 0 if aged 71-75 years * Life expectancy of more than 3 months * Adequate haematological function: ANC >= 1.5 x 109/L; platelets >= 100 x 109/L, Hb >= 9 g/dL * INR <= 1.5 and aPTT <= 1.5 x ULN within 7 days prior to starting study treatment * Adequate liver function: serum bilirubin <= 1.5 x ULN; alkaline phosphatase and transaminases <= 2.5 x ULN (in case of liver metastases < 5 x ULN) * Serum Creatinine <= 1.5 x ULN * Urine dipstick for proteinuria < 2+. If urine dipstick is >= 2+, 24- hour urine must demonstrate <= 1 g of protein in 24 hours * Previous adjuvant chemotherapy is allowed if more than 12 months have elapsed between the end of adjuvant therapy and first relapse * At least 6 weeks from prior radiotherapy and 4 weeks from surgery Exclusion Criteria: * Prior palliative chemotherapy * Prior treatment with bevacizumab * Bowel obstruction (or subobstruction) * History of inflammatory enteropathy or extensive intestinal resection (> hemicolectomy or extensive small intestine resection with chronic diarrhea) * Symptomatic peripheral neuropathy > 2 grade NCIC-CTG criteria * Presence or history of CNS metastasis * Active uncontrolled infections * Active disseminated intravascular coagulation * Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to treatment, or anticipation of the need for major surgery during the course of the study * Central Venous Access Device (CVAD) for chemotherapy administration inserted within 2 days prior to study treatment start * Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin cancer or in situ carcinoma of the cervix * Clinically significant cardiovascular disease, for example cerebrovascular accidents (CVA) (<= 6 months before treatment start), myocardial infarction (<= 6 months before treatment start), unstable angina, NYHA >= grade 2 chronic heart failure (CHF), uncontrolled arrhythmia * Uncontrolled hypertension * 24-hour urine protein > 1 g if dipstick > 2+ * History of thromboembolic or hemorrhagic events within 6 months prior to treatment * Evidence of bleeding diathesis or coagulopathy * Serious, non healing wound/ulcer or serious bone fracture * No therapeutic anticoagulation or antiplatelet agents or NSAID with anti-platelet activity (aspirin <= 325 mg/day allowed) * Pregnancy or lactation * Fertile women (< 2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception

Study Objectives The study is a pilot study in the feasibility of a diagnostic technique. There is no current data on detection of cisplatin in cancer cells derived from human urine. This study will generate preliminary data so that future studies may be done with more definitive end points in mind. Conditions: Bladder Cancer Intervention / Treatment: DIAGNOSTIC_TEST: mass spectrometry Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Patients must have a diagnosis of bladder cancer * Patients must be undergoing their first cycle of cisplatin based chemotherapy due to metastatic disease or as pre-operative treatment before cystectomy * Patients with a diagnosis of bladder cancer who will not be undergoing chemotherapy * Patients must have demonstrated positive urinary cytology prior to inclusion in the study Exclusion Criteria: * Patients who do not have bladder cancer.

Study Objectives The investigators' objective is to assess the efficacy of the combined treatment with enalapril and carvedilol in the prevention of left ventricular systolic dysfunction in patients with hematological malignancies submitted to intensive chemotherapy with potential cardiotoxicity. The hypothesis is that these drugs administered during chemotherapy may prevent left ventricular systolic dysfunction. Conditions: Acute Myeloid Leukemia, Precursor-cell Lymphoblastic Leukemia-Lymphoma, Lymphoid Neoplasm, Multiple Myeloma, Lymphoma, Autologous Hematopoietic Stem Cell Transplantation Intervention / Treatment: DRUG: Enalapril and carvedilol Location: Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Adult patients 18-70 years old * Sinus rhythm * Normal LVEF (>=50%) * Patients recently diagnosed of acute leukemia to be submitted to intensive chemotherapy or * Patients with other hemopathies submitted to autologous peripheral blood stem cell transplantation * Signed informed consent Exclusion Criteria: * Congestive heart failure * LVEF<50% * Coronary artery disease, * significant valvulopathy or myocardiopathy * Renal failure (MDRD<30) * Liver failure * Ongoing or expected need to be treated with angiotensin-converting enzyme inhibitors (ACE-i),angiotensin II receptor blockers (ARB) or beta-blockers * Prior allergy to ACEI or ARB * Systolic blood pressure <90 mmHg * Asthma * Auriculoventricular (AV) block or sinus bradycardia (HR<60 bpm) * Persistent atrial fibrillation * Need to be treated with Class I antiarrhythmic drugs * Pregnancy * Inability or unwillingness to give unformed consent

Study Objectives PLX3397 is a selective inhibitor of Fms, Kit, and oncogenic Flt3 activity. The primary objective of this study is to evaluate the safety and pharmacokinetics of orally administered PLX3397 in patients with advanced, incurable, solid tumors in which these target kinases are linked to disease pathophysiology. The secondary objective is to measure the pharmacodynamic activity of PLX3397 via blood, plasma and urine biomarkers of Fms activity. Conditions: Solid Tumor Intervention / Treatment: DRUG: PLX3397 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 and older * Solid tumors refractory to standard therapy * For the Extension cohorts, patients must have measurable disease by RECIST criteria and meet the following disease-specific criteria: * For advanced or recurrent mucoepidermal carcinoma (MEC) of the salivary gland, patients must not be candidates for curative surgery or radiotherapy. * For pigmented villo-nodular synovitis (PVNS), patients must have a histologically confirmed diagnosis of inoperable progressive or relapsing PVNS, or resectable tumor requesting mutilating surgery, as well as demonstrated progressive disease in the last 12 months. * For gastrointestinal stromal tumors (GIST), patients must have failed previous therapy with imatinib and sunitinib. Patients with known PDGFR mutations are excluded, but mutation testing is not required for study entry. * For anaplastic thyroid cancer (ATC), patients must have histologically or cytologically diagnosed advanced ATC. * For metastatic solid tumors with documented malignant pleural and/or peritoneal effusions, patients must not be receiving specific therapy for the effusion or have an indwelling drain. * Eastern Cooperative Oncology Group performance status 0 or 1 * Life expectancy >= 3 months * Adequate hepatic, renal, and bone marrow function Exclusion Criteria: * Specific anti-cancer therapy within 3 weeks of study start * Uncontrolled intercurrent illness * Refractory nausea or vomiting, or malabsorption * Mean corrected QT interval (QTc) >= 450 msec (for males) or QTc >= 470 msec (for females)

Study Objectives Gynecological cancer is cancer that starts in the female reproductive organs. Pain in gynecological cancer can be caused by an underlying malignancy or surgical procedure as well as chronic pain associated with malignancy and sequelae of the therapy given. Gynecological cancer patients often experience moderate to severe pain and use higher levels of opioids than patients diagnosed with other cancers. More than two thirds of patients with advanced cancer experience severe pain and up to half of these patients report that their pain is not well controlled. This study aims to analyze the effectiveness of electroacupuncture plus standard therapy on pain intensity (VAS score), changes in analgesic dose, and quality of life (QLQ C-30 EORTC score) in patients with gynecological cancer pain compared to standard therapy alone. Conditions: Gynecologic Cancer, Cancer Related Pain, Cancer Pain Intervention / Treatment: OTHER: Electroacupuncture Location: Indonesia Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * Female 18 to 65 years old * Gynecocal cancer with pain >= 4 acording Visual Analog scale and receive analgetic medicine * The pain cause by 1. direct from cancer 2. Treatment proces surgery, radiotherapy, chemotherapy, paliatif treatment, supportive treatment 3. Adverse reaction form treatment and intoxication Exclusion Criteria: * Emergency case patient with hemodynamic instable * Patient with uncooperative behavior because ith serious psychological disorders, no currently undergoing psychiatric treatment, aggressive behavior, that not allowed for acupuncture. * Patients with blood clotting disorders, with platelets <50.000 and in neutropenic condition with <1000 neutrophils. * The patient has an allergy to stainless steel acupuncture needles. Wounds at the acupuncture point puncture sites, skin infections in the ears. On patients with eczema on the ears, external otitis or psoriasis. * There is a tumor in the area that will be stabbed and stimulated in the stomach pregnant women, close to the heart, or in the area of the carotid sinus lymphedema, insertion into the prosthesis. * Patients with heart rhythm disorders. The patient uses a pace maker.

Study Objectives The large-scale phase IV study aims to verify the safety and efficacy of apatinib in patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma after failure of two lines of chemotherapy. Apatinib initiated at a recommended dose of 850mg. However, the starting dose was decided by investigator's choice based on patients' condition. Dose interruption and dose reduction were allowed according to the product label. Treatment continued until disease progression, intolerable toxicity, withdrawal of informed consent, or at investigators' discretion. The primary endpoint was safety, which was assessed by recording the incidence and severity of adverse events. Conditions: Advanced Gastric or Gastroesophageal Junction Adenocarcinoma Intervention / Treatment: DRUG: ApatinibTablets Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Age: 18 to75 years old; * Pathologically diagnosed with advanced gastric cancer (including adenocarcinoma of the gastroesophageal junction); * Failure of prior therapy (during or after treatment) in patients who have received at least two prior chemotherapy regimens; * ECOG PS of 0-2; * Major organ function has to meet the following criteria: For results of blood routine test (without blood transfusion within 14 days): HB >= 90g / L ANC >= 1.5 × 109 / L PLT >= 80 × 109 / L Biochemical tests results: Bilirubin <1.25 times the upper limit of normal (ULN) ALT and AST <2.5 × ULN; liver metastases, if any, the ALT and AST<5 × ULN Serum Cr <= 1 × ULN endogenous creatinine clearance>50ml/min (Cockcroft-Gault formula) * An expected survival of >= 3 months; * Patient received apatinib treatment regimen at investigators' discretion; * Patient has to voluntarily join the study and sign the Informed Consent Form for the study; * Pregnancy test (serum or urine) has to be performed for woman of childbearing age within 7 days before enrolment and the test result must be negative. They shall take appropriate methods for contraception during the study until the 8th week post the last administration of study drug. For men, (previous surgical sterilization accepted), shall agree to take appropriate methods of contraception during the study until the 8th week post the last administration of study drug. Exclusion Criteria: * Subjects with uncontrolled arterial hypertension (systolic blood pressure> 140 mmHg and diastolic blood pressure > 90 mm Hg) despite standard medical management; Grade >= 2 coronary heart disease; Grade >= 2 arrhythmia (including QT interval prolongation, for man > 450 ms, for woman > 470 ms), as well as Grade >= 2 cardiac dysfunction; * Factors that could have an effect on oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction); * Subjects with high gastrointestinal bleeding risk, including the following conditions: presence of active ulceration combined with a positive fecal occult blood test (++);history of hematemesis and melena within three months before enrollment; unresected primary lesion in stomach with positive fecal occult blood test (+), ulcerated gastric carcinoma with massive alimentary tract bleeding risk judged by PIs based on gastric endoscopy finding; * Abnormal coagulation (INR>1.5、APTT>1.5 UNL), with tendency of bleeding; * Presence of central nervous system metastases; * Pregnant or lactating women; * Other conditions regimented at investigators' discretion.

Study Objectives Primary Objectives: 1. To determine the feasibility and toxicity profile of administering liposomal 9-Nitro-20-(S)-Camptothecin (L9-NC) by aerosol alone and in combination with temozolomide. 2. To determine the effectiveness of L9-NC given by aerosol in combination with temozolomide in patients with solid tumors involving the lungs. Conditions: Ewing's Sarcoma Intervention / Treatment: DRUG: Temozolomide, DRUG: L9-NC Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * All patients, 10 years of age or older, with primary or metastatic cancer in the lungs, who have failed or progressed on front line therapy and have no standard therapies available for treatment are eligible. Patients may also have disease in other sites, but must have current lung involvement to be eligible. * Patients should have adequate bone marrow function, defined by: absolute peripheral granulocyte count of >= 1500 cells/mm^3, platelet count > 100,000 platelets/mm^3, and Hgb > 8.0 g/dl. For patients with documented bone marrow involvement, the following counts are acceptable for enrollment: absolute peripheral granulocyte count of > 1000 cells/mm^3 , platelet count > 75,000 platelets/mm^3. * Patients should have adequate hepatic function, defined by: total bilirubin < 2 mg/dl and ALT or AST < 2x upper limit of normal. * Patients should have adequate renal function, defined by serum creatinine <= 2 mg/dl. * Patients must have adequate pulmonary function, as defined by a pulmonary function test with: >= 50% FVC, >= 50% FEV1 and >= 50% DLCO of predicted values Exclusion Criteria: * Patients with symptomatic brain metastases. * Pregnant women or nursing mothers. Patients of child bearing potential must use adequate contraception. * Patients receiving concurrent chemotherapy. * Patients may not receive concurrent radiation therapy to the chest during cycles 1-3. Radiation therapy to disease in other areas of the body is permissible at any time, but such lesions will not be evaluable for response. Although patients who have received prior radiation to the chest are eligible, patients should be at least 4 weeks from prior radiation to the chest. Any chest lesion treated with radiation must have progressed to be considered measurable for this study. * Patients with severe medical problems such as uncontrolled diabetes mellitus (glucose consistently greater than 200 mg/dl, or Hemoglobin A1c greater than 8%) or symptomatic cardiovascular disease (New York class III) or active infections requiring IV antibiotics are not eligible for this trial. * Patients requiring oxygen.

Study Objectives The study aim is to compare safety and efficacy of high-dose lenalidomide regimen, sequential azacitidine and lenalidomide and an azacitidine in persons ≥65 years with newly-diagnosed acute myeloid leukemia (AML). Conditions: Acute Myeloid Leukemia, Acute Myelogenous Leukemia Intervention / Treatment: DRUG: Azacitidine, DRUG: Lenalidomide, OTHER: Best Supportive Care (BSC) Location: United States, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Newly diagnosed acute myeloid leukemia (AML), AML with antecedent hematologic disorder or therapy-related AML * Male or female subjects aged >= 65 * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 * White blood cell (WBC) count <= 10 x 10⁹/L at screening Exclusion Criteria: * Previous treatment with azacitidine, decitabine, cytarabine or lenalidomide * Previous cytotoxic or biologic treatment of any kind for AML or prior use of targeted therapy agents. * Suspected or proven acute promyelocytic leukemia * Prior bone marrow or stem cell transplantation * Candidate for allogeneic bone marrow or stem cell transplantation * AML antecedent hematologic disorder such as chronic myelogenous leukemia or myeloproliferative neoplasms * Presence of malignant disease within the previous 12 months with exceptions

Study Objectives The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as LY3023414 in combination with enzalutamide in men with prostate cancer. Conditions: Prostate Cancer Metastatic Intervention / Treatment: DRUG: LY3023414, DRUG: Enzalutamide, DRUG: Placebo Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Histologically or cytologically confirmed adenocarcinoma of the prostate. * Metastatic disease documented by positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI) scan. * Prostate cancer progression documented by PSA and/or radiographic progression according to prostate cancer working group 2 (PCWG2). * Prior abiraterone treatment completed at least 4 weeks prior to cycle 1 day 1. Participants must have failed prior abiraterone treatment. * Surgically or medically castrated, with testosterone levels of < 50 nanograms/deciliter. * Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1. * Ability to swallow the study drugs whole. * Adequate hematologic function. * Adequate coagulation parameters, defined as international normalization ratio (INR) <= 2. * Availability of tumor tissue from any time since diagnosis of prostate cancer disease. If no tumor samples are available the participant might still be eligible following discussion between the investigator and the medical monitor. Exclusion Criteria: * Prior cytotoxic chemotherapy, immunotherapy, a PI3K/AKT/mTOR agent (including TORC1 and TORC2 inhibitors), or RA 223 dichloride for the treatment of castration resistant prostate cancer (CRPC). Participants may have received docetaxel in the hormone-sensitive setting. * Prior investigational new generation potent anti-androgen therapy (such as ARN 509). * Prior treatment with enzalutamide. * Pathological finding consistent with small cell carcinoma of the prostate. * Prior systemic treatment with an azole drug (fluconazole, itraconazole) within 4 weeks of cycle 1 day 1. * Known brain metastasis. * History of (a) seizure or any condition that may predispose to seizure (prior cortical stroke or significant brain trauma); (b) loss of consciousness or transient ischemic attack within 12 months prior to day 1 of cycle 1. * Uncontrolled hypertension (systolic blood pressure [BP] >= 160 millimeters of mercury [mmHg] or diastolic BP >= 95 mmHg). * Have serious pre-existing medical conditions (at the discretion of the investigator). * Have known acute or chronic leukemia or current hematologic malignancies that, in the judgment of the investigator and sponsor, may affect the interpretation of results. * Have insulin-dependent diabetes mellitus. Participants with a type 2 diabetes mellitus are eligible if adequate control of blood glucose level is obtained by oral anti-diabetics as documented by hemoglobin A1c <7%. * Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, vomiting, grade >=2 diarrhea, and malabsorption syndrome). * Have a history of New York Heart Association (NYHA) Class >=3, QTc interval > 480 milliseconds (ms) on screening electrocardiogram (ECG) per Friderica's formula, unstable angina, or myocardial infarction (MI) in 6 months prior to study drug administration. * Clinically significant electrolyte imbalance >= grade 2. * Currently receiving treatment with therapeutic doses of warfarin sodium. * Have initiated treatment with bisphosphonates or approved receptor activator of nuclear factor kappa-B ligand (RANK-L) targeted agents (e.g. denosumab) <=28 days prior to day 1 of cycle 1. * Concurrent serious infections requiring parenteral antibiotic therapy. * Have a second primary malignancy that in the judgment of the investigator and medical monitor may affect the interpretation of results. * Have an active, known fungal, bacterial, and/or known viral infection.

Study Objectives Multi-center, single-arm Phase 1b study designed to evaluate safety and tolerability of ARQ 197 in cirrhotic patients with HCC. Conditions: Cirrhosis, Hepatocellular Carcinoma Intervention / Treatment: DRUG: ARQ 197 Location: United States, Italy, Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Written informed consent granted prior to initiation of any study-specific screening procedures, given with the understanding that the patient has the right to withdraw from the study at any time, without prejudice * 18 year of age or older * Histologically or cytologically confirmed HCC (not required if: a hepatic lesion is >2cm in diameter , is suggestive of HCC at radiology and α-fetoprotein (AFP) is > 200 mg/mL) * Barcelona Clinic Liver Cancer (BCLC) staging Category27 A, B or C that can not benefit from treatments of established efficacy and/or higher priority * Cirrhotic status of Child-Pugh Class A and B without ascites or with slight ascites that can be recognized only by imaging techniques and/or managed easily with diuretics (e.g. 100 mg spironolactone per day and/or furosemide 40 mg/day) * Cirrhotic status confirmed by one of the following methods/evidence: * Biopsy * Endoscopy showing gastrointestinal tract varices * Evidence of portal hypertension on imaging studies such as dilated portal vein, collateral circulation * ECOG PS <=1 * Not more than two prior systemic regimens for HCC and the last treatment must have been completed >=4 weeks prior to first dose of ARQ 197 * Local or loco-regional therapy (i.e., surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed >=4 weeks prior to first dose of ARQ 197 * Measurable disease as defined by revised Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Tumor lesions selected as target lesion(s) at baseline should not have been previously treated with local therapy (naïve tumor lesion) * Adequate bone marrow, liver, and renal functions, defined as: * Platelet count >= 60 × 10^9/L * Hemoglobin >= 8.5 g/dL * Absolute neutrophil count (ANC) >=1.5 × 10^9/L * Total bilirubin <= 3 mg/dL * Alanine transaminase (ALT) and aspartate transaminase (AST) <= 5 × upper limit of normal (ULN) * Serum creatinine <=1.5 × ULN * International normalized ratio (INR) <= 2.3 or PT <= 6.0 seconds above control. Patients who are therapeutically anticoagulated with an agent such as coumadin or heparin are allowed to participate provided that no prior evidence of underlying abnormality exists in these parameters * Albumin >= 2.8 g/dL * Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug * Male and female subjects of child-bearing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received Exclusion Criteria: * Previous or concurrent cancer that is distinct from HCC in primary site or histology, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated >3 years prior to enrollment is permitted * History of cardiac disease: congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD); previously diagnosed bradycardia or other cardiac arrhythmia, or uncontrolled hypertension; myocardial infarction occurred within 6 months prior to study entry (myocardial infarction occurred > 6 months prior to study entry is permitted) * Active clinically serious infections defined as >= Grade 2 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 * Substance abuse, medical, psychological or social conditions that may, in the opinion of the Investigator, interfere with the patient's participation in the study or evaluation of the study results * Any condition that is unstable or which could jeopardize the safety of the patient and his/her protocol compliance * Known HIV (human immunodeficiency virus) infection * Pregnancy or breast-feeding * History of liver transplant * Inability to swallow oral medications * Clinically significant gastrointestinal bleeding occurring <=4 weeks prior to first dose of ARQ 197

Study Objectives The MROC Study seeks to evaluate and compare from the patient's point of view the leading options for breast reconstruction after mastectomy. This study will help patients, physicians, payers and policy makers better understand the various surgeries available for breast reconstruction. Although many women choose reconstruction, the number of options as well as their pros and cons can make decision making difficult and stressful. From this research, we hope to learn more about what works best for patients undergoing these operations. Conditions: Breast Cancer Location: United States, Canada Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Women who present themselves for reconstruction at one of 11 MROC centers * Women undergoing one of the following types of breast reconstruction after mastectomy: tissue expander/implant, LD flap (with, or without implant), PTRAM flap, FTRAM flap, DIEP flap, S-GAP flap, I-GAP flap or SIEA flap. * Immediate or delayed reconstruction * Unilateral or bilateral reconstructions. * Women receiving mastectomy for cancer prophylaxis, without history of breast cancer, will be eligible to participate. Exclusion Criteria: * Patients electing reconstruction following complications of breast augmentation, mastopexy (breast lift), or breast reduction will not be recruited for the study. * Procedures performed following previously failed attempts at breast reconstruction will be excluded from the study, due to potential confounding by these previous surgeries.

Study Objectives The purpose of this study is to determine the safety of an extracellular signal regulated kinase (ERK1/2) inhibitor LY3214996 administered alone or in combination with other agents in participants with advanced cancer. Conditions: Advanced Cancer, Metastatic Melanoma, Metastatic Non-small Cell Lung Cancer, Colorectal Cancer Intervention / Treatment: DRUG: LY3214996, DRUG: Midazolam, DRUG: Abemaciclib, DRUG: Nab-paclitaxel, DRUG: Gemcitabine, DRUG: Encorafenib, DRUG: Cetuximab Location: United States, Japan, Australia, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Have advanced or metastatic cancer (solid tumors) and be an appropriate candidate for experimental therapy. * Part B (No Longer Enrolling Participants): Have advanced or metastatic cancer with an activating mitogen-activated protein kinase pathway alteration, BRAF mutant metastatic melanoma refractory to or relapsed after treatment with RAF and/or MEK inhibitors, metastatic melanoma with a NRAS mutation, or BRAF mutant NSCLC. * Part C: Advanced, unresectable cancer (dose escalation) and advanced, unresectable, or metastatic non-small cell lung cancer with a BRAF or RAS mutation, or NRAS mutant melanoma (dose expansion). * Part D (No Longer Enrolling Participants): Have metastatic pancreatic ductal adenocarcinoma (dose escalation and dose expansion). * Part E: Metastatic BRAF V600E colorectal cancer. * Have discontinued previous treatments for cancer and have resolution, except where otherwise stated in the inclusion criteria, of all clinically significant toxic effects of prior chemotherapy, surgery, or radiotherapy to Grade <=1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0. * Have adequate organ function. * Have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) scale. Exclusion Criteria: * Have serious preexisting medical conditions. * Have a known human immunodeficiency virus (HIV) infection or known activated/reactivated hepatitis A, B, or C. * Have symptomatic central nervous system malignancy or metastasis. * Have current hematologic malignancies, acute or chronic leukemia. * Have a second primary malignancy that in the judgment of the investigator or Lilly may affect the interpretation of results. * Have prior malignancies. Participants with carcinoma in situ of any origin and participants with prior malignancies who are in remission and whose likelihood of recurrence is very low, as judged by the Lilly clinical research physician, are eligible for this study. * Have a mean QT interval corrected for heart rate (QTc) of >=470 milliseconds on screening electrocardiogram (ECG) as calculated using the Bazett's formula at several consecutive days of assessment. * Have participated, within the last 28 days in a clinical trial involving an investigational product or are currently enrolled in a clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study. * Have previously completed or withdrawn from this study or any other study investigating an ERK1/2 inhibitor. * If female, is pregnant, breastfeeding, or planning to become pregnant. * Have history or findings of central or branch retinal artery or venous occlusion with significant vision loss or other retinal diseases that cause current visual impairment or would likely cause visual impairment over the time period of the study. * Currently using concomitant medications that are strong inhibitors or inducers of CYP3A4. * Part C: have serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study, including interstitial lung disease (ILD) or severe dyspnea at rest or requiring oxygen therapy. * Part C4 NRAS Melanoma: have previously completed or withdrawn from a study investigating a MEK inhibitor.

Study Objectives This is an open-label Phase 1 dose escalation study of OMP-59R5 in subjects with previously treated solid tumors for which there is no remaining standard curative therapy and no therapy with a demonstrated survival benefit. Up to 44 subjects will be enrolled at up to 2 centers. Subjects will be assessed for safety, immunogenicity, pharmacokinetics, biomarkers, and efficacy. No formal interim analyses will be performed. Prior to enrollment, subjects will undergo screening to determine study eligibility. Upon enrollment, subjects will receive intravenous (IV) infusions of OMP-59R5 at a assigned dosing schedule for 56 days. After 56 days, subjects will be assessed for disease status. If there is no evidence of disease progression or if the tumor is smaller, then subjects may continue to receive IV infusions of OMP-59R5 every week until disease progression. Dose escalation will be conducted to determine the maximum tolerated dose (MTD). No dose escalation or reduction will be allowed within a dose cohort. The first 2 subjects enrolled in a cohort will not be treated on the same day. The dose may be administered at any time during the day. Three subjects will be treated at each dose level if no dose-limiting toxicities (DLTs) are observed. The first 2 subjects in each cohort will not be started on OMP-59R5 on the same day. If 1 of 3 subjects experiences a DLT, that dose level will be expanded to 6 subjects. If 2 or more subjects experience a DLT, no further subjects will be dosed at that level and 3 additional subjects will be added to the preceding dose cohort unless 6 subjects have already been treated at that dose level. Subjects will be assessed for DLTs from the time of the first dose through 28 days. Dose escalation for newly enrolled subjects, if appropriate, will occur after all subjects in a cohort have completed their Day 28 DLT assessment. Subjects with stable disease or a response at Day 56 will be allowed to continue to receive weekly doses of OMP-59R5 until disease progression. An additional 14 subjects will be enrolled at the highest dose level that result in \<2 of the 6 subjects experiencing a DLT. Conditions: Solid Tumors Intervention / Treatment: DRUG: OMP-59R5 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: * Subjects must have a histologically confirmed malignancy that is metastatic or unresectable for which there is no remaining standard curative therapy and no therapy with a demonstrated survival benefit. In addition, subjects must have a tumor that is at least 1 cm in a single dimension and is radiographically apparent on CT or MRI. * Subjects must have received their last chemotherapy, biologic, or investigational therapy at least 4 weeks prior to enrollment, 6 weeks if the last regimen included BCNU or mitomycin C. * Age >18 years * ECOG performance status <2 (see Appendix B) * Life expectancy of more than 3 months * Subjects must have normal organ and marrow function as defined below: * Absolute neutrophil count >1000/mL * Hemoglobin >9.0 g/dL * Platelets >100,000/mL * Total bilirubin <1.5 X institutional upper limit of normal (ULN) * AST (SGOT) and ALT (SGPT) < 3 X institutional ULN (for subjects with hepatic metastases < 5 X institutional ULN) * PT and PTT within 1.5 X institutional ULN * Creatinine <1.5 X institutional ULN OR * Creatinine clearance >60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal * Women of childbearing potential must have had a prior hysterectomy or have a negative serum pregnancy test and be using adequate contraception prior to study entry and must agree to use adequate contraception from study entry through at least 6 months after discontinuation of study drug. Men must also agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and from study entry through at least 6 months after discontinuation of study drug. Should a woman enrolled in the study or a female partner of a man enrolled in the study become pregnant or suspect she is pregnant while participating in this study or within 6 months after discontinuation of study, she should inform the Investigator immediately. * Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * Subjects receiving any other investigational agents * Subjects with brain metastases (subjects must have a CT scan or MRI of the head within 28 days prior to enrollment to rule out brain metastases), uncontrolled seizure disorder, or active neurologic disease * History of a significant allergic reaction attributed to humanized or human monoclonal antibody therapy * Significant intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Pregnant women or nursing women * Subjects with known HIV infection * Known bleeding disorder or coagulopathy * Subjects receiving heparin, warfarin, or other similar anticoagulants, except for subjects on low molecular weight heparin for DVT/PE prophylaxis. Note: Subjects may be receiving low-dose aspirin and/or non-steroidal anti-inflammatory agents. * New York Heart Association Classification II, III, or IV * Subjects with a blood pressure of >140/90 mmHg. The blood pressure must be taken three times 10 minutes apart. Subjects taking antihypertensive medications must be taking <= 2 medications to obtain this level of blood pressure control. * Subjects with EKG evidence of ischemia or >= Grade 2 ventricular arrhythmia, subjects who have a history of acute myocardial infarction within 6 months, or subjects with unstable angina. * Subjects with known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease. * Subjects with known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease. * Subjects with >1 grade 1 diarrhea.

Study Objectives This multicenter phase II trial is designed to study the unique combination of chemotherapy (irinotecan./carboplatin) and bevacizumab in the extensive-stage setting. This clinical setting seems ideal for evaluation of the role of bevacizumab in delaying progression and prolonging survival. Conditions: Carcinoma, Small Cell Lung Intervention / Treatment: DRUG: irinotecan, DRUG: carboplatin, 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: * Histologically confirmed small cell lung cancer,extensive stage disease. * Measurable or evaluable disease * No previous chemotherapy * Able to perform activities of daily living with minimal assistance * Adequate hematological, live and kidney function * Provide written informed consent Exclusion Criteria: * Limited stage disease * PEG or G tubes * Hemoptysis * Abdominal fistula, perforation, or abscess within the previous 6 months * Women who are pregnant or lactating * Proteinuria * Serious nonhealing wound, ulcer, or bone fracture * Evidence of bleeding diathesis or coagulopathy * Uncontrolled or serious cardiovascular disease * Uncontrolled brain metastasis * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days; Fine needle aspiration within 7 days * Patients requiring full-dose anticoagulation must be on a stable dosing schedule prior to enrollment

Study Objectives The overall objective of this study is to obtain data to evaluate whether high-resolution imaging of barrett's esophagus in vivo can assist clinicians in detecting dysplastic (precancerous) areas. This is a pilot study of an novel technology, a miniaturized microscope device which can be used during upper endoscopy to image the gastrointestinal epithelium. This is an exploratory, not a comparative, study designed to evaluate the feasibility of using this instrument in Barrett's esophagus. Conditions: Barrett's Esophagus Intervention / Treatment: DRUG: Proflavine Hemisulfate Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: EARLY_PHASE1 Primary Purpose: SCREENING Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Barrett's without dysplasia * Barrett's with dysplasia * Esophageal Adenocarcinoma Exclusion Criteria: * Subjects unfit for standard upper endoscopy * Subjects currently receiving chemo or radiation treatment * Subject currently receiving PDT or ablation

Study Objectives The purpose of this study is to estimate the relative bioavailability of TAK-931 tablets in reference to powder-in capsule (PIC) and to assess the effect of food and esomeprazole on the pharmacokinetics (PK) of TAK-931 as a tablet. Conditions: Neoplasms, Advanced Solid Intervention / Treatment: DRUG: TAK-931 PIC, DRUG: TAK-931 Tablet, DRUG: Esomeprazole Location: Netherlands Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: OTHER Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * Adult participants with histologically or cytologically confirmed metastatic or locally advanced or metastatic solid tumors for whom there is no available standard treatment with proven survival benefit, this therapy is not indicated, or it is refused by the participant. Based on the nonclinical data, the following indications may have a higher probability of clinical benefit: high-grade serous ovarian cancer, uterine carcinosarcoma, squamous esophageal cancer, squamous non-small cell lung carcinoma (NSCLC), rectal adenocarcinoma, and in general tumors with known tumor protein 53 (TP53) gene mutations. For any of these preferred indications, participants should have exhausted standard therapeutic options with a proven survival benefit. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. * Recovered to Grade 1 or baseline from all toxic effects of previous therapy (except alopecia or neuropathy). * Suitable venous access for the study-required blood sampling including PK and pharmacodynamic sampling. * Must have a radiographically or clinically evaluable tumor, but measurable disease as defined by RECIST v1.1 is not required for participation in this study. Exclusion Criteria: * Participants who require continuous use of proton pump inhibitors (PPIs) or histamine-2 (H2) receptor antagonists and participants who are taking PPIs within 5 days before the first dose of study drug. * Treatment with clinically significant enzyme inducers, such as phenytoin, carbamazepine, enzalutamide, mitotane, ritonavir, rifampin, or St John's wort within 14 days before the first dose of study drug. * With treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after central nervous system-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or CT) during the screening period. * Part 2 only: known hypersensitivity to PPIs (example, angioedema or anaphylaxis have occurred). * Part 2 only: not being able or willing to take one high fat breakfast as indicated in the protocol.

Study Objectives This is a study, where the efficacy of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) against peritoneal metastases will be evaluated. Furthermore, this study will focus on the best evaluation method, where both Quality of Life questionnaires, repeated histology, cytology and MRI will be used. Conditions: Peritoneum; Carcinomatosis, Peritoneal Neoplasms, Peritoneal Metastases, Chemotherapy Effect, Chemotherapeutic Toxicity, Quality of Life, Histologic Progression Intervention / Treatment: DRUG: PIPAC Location: Denmark Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histological or cytological verified gastrointestinal-, ovarian- or primary peritoneal malignancy (based on tissue from the primary tumor and/or its metastases). * Ovarian cancer patients must be platinum resistant and have completed at least one line of chemotherapy for platinum resistant disease. * Radiological, histological or cytological evidence of PC. * No indication for CRS and HIPEC (according to National Guidelines). * Performance status 0-1. * No more than a single extra-peritoneal metastasis. * Age > 18 years. * Females must be post-menopausal * Written informed consent must be obtained according to the local Ethics Committee requirements. Exclusion Criteria: * Symptomatic small bowel obstruction (i.e. total parenteral nutrition, nasogastric tube). * Previous treatment with maximum cumulative doses of doxorubicin, daunorubicin, epirubicin, idarubicin, and/or other anthracyclines and anthracenediones. * A history of allergic reaction to platinum containing compounds or doxorubicin. * Renal impairment, defined as GFR < 40 ml/min, (Cockcroft-Gault Equation). * Myocardial insufficiency, defined as NYHA class > 2. * Impaired liver function defined as bilirubin >= 1.5 x UNL (upper normal limit). * Inadequate hematological function defined as ANC <= 1.5 x 109/l and platelets <= 100 x109/l.

Study Objectives The purpose of this study is to track outcomes and complications of patients at IUMC referred by physicians for EUS-guided pancreatic cyst ablation. This information is essential in order to disseminate future published information to physicians about this technique. A database will be created to track these patients undergoing an already scheduled/planned procedure. Phone calls at selected intervals will be made following the procedure to track any complications that occur Conditions: Pancreatic Cyst, Pancreatic Intraductal Papillary-Mucinous Neoplasm, Cystadenoma, Mucinous, Papillary Mucinous Cystadenoma, Borderline Malignancy Intervention / Treatment: PROCEDURE: 98% Ethanol & Paclitaxel injection 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 referred between January 2009 and February 2016 to EUS at IUMC for pancreatic cyst ablation and with no contraindications for anticipated safe and successful performance of the procedure. * Patient at least 18 years of age. Exclusion Criteria: * Investigator deems cyst does not meet safety or need for cyst ablation. * Subject not competent to sign consent

Study Objectives The purpose of this project is to determine if a new combination of drugs, erlotinib (Tarceva™) and bevacizumab is safe and effective for treating women diagnosed with ovarian cancer whose cancer has progressed while on prior standard chemotherapy treatment with a taxane (paclitaxel or docetaxel) and a platinum (cisplatin or carboplatin). Conditions: Ovarian Neoplasms Intervention / Treatment: DRUG: bevacizumab, DRUG: erlotinib 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: * Histologically or pathologically confirmed diagnosis of epithelial carcinoma of the ovary or primary peritoneal carcinoma. * Relapsed after prior therapy with taxane and platinum-based therapy, within 6 months of completing, or had a best response of stable disease during no more than two prior chemotherapy treatments with a platinum (either cisplatin or carboplatin) and a taxane (paclitaxel or docetaxel). These agents may have been administered concurrently or sequentially. Besides the primary chemotherapy, two additional chemotherapy regimens are allowed. Hormonal therapy is allowed and will not be counted as a chemotherapy regimen. * Up to one year of consolidation treatment with intraperitoneal and intravenous administered chemotherapy drugs to consolidate a clinical complete remission is allowed. * Patients must have elevated CA-125 or measurable disease. * For patients who do not have RECIST measurable disease, an elevated CA-125 (greater than two times the institutional upper limit of normal) will be required for enrollment. * Debulking surgery for relapsed disease is allowed but must be completed at least 28 days prior to the first day of study therapy. Patient must have recovered from all side effects of surgery including a completely healed surgical incision. * Patient must have a Zubrod performance status of 0-1. * Patient must have adequate hepatic function as defined by: * a serum bilirubin <=1.5 x the institutional upper limit of normal (IULN), * SGOT or SGPT <=2.5 x the institutional upper limit of normal obtained within 14 days prior to start of therapy * Patient must have an adequate renal function as defined by: * a serum creatinine <=1.5 x the institutional upper limit of normal obtained within 14 days prior to start of therapy and a urine protein:creatinine (UPC) ratio of <= 1.0. * Patients must be able to take oral medications * Patients may not have ongoing problems with bowel obstruction or short bowel syndrome characterized by grade 2 or greater diarrhea or malabsorptive disorders. * Patients must have the following hematological criteria: * Hemoglobin of >10gm/dL, * White blood cell count >2500, * Platelets >80,000 * Patients must be >= 18 years of age. Exclusion Criteria: * Subjects with mixed mullerian tumors and borderline ovarian tumors are excluded. Patients with a history of borderline ovarian tumors that have evolved into higher grade tumors will be eligible. * The patient must not have received chemotherapy, biologic therapy or any other investigational drug for any reason within 28 days prior to start of therapy and must have recovered from toxicities of prior therapy to grade 1 or less with the exception of alopecia. * Patient must not be pregnant or nursing because bevacizumab or erlotinib maybe harmful to the developing fetus and newborn. Women of reproductive potential must have a negative serum pregnancy test within 7 days prior to study consent. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug. * Patients should not have psychological, familial, sociological, or geographical conditions that do not permit medical follow-up or compliance with the study protocol. * Except for cancer-related abnormalities, patients should not have unstable or preexisting major medical conditions. * Patients should not have any medical life-threatening complications of their malignancies * Patients should not have a known severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease, active uncontrolled infection, or HIV) * Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study. * Baseline blood pressure of < or equal to 150/100 mmHg. Patients with a blood pressure reading above this level should be initiated on anti-hypertensive therapy and may be considered for protocol treatment when their blood pressure is adequately controlled. * New York Heart Association (NYHA) Grade II or greater congestive heart failure * History of myocardial infarction, cerebrovascular accident, transient ischemic attack, or unstable angina within 6 months * Clinically significant peripheral vascular disease * Evidence of bleeding diathesis or coagulopathy * Presence of central nervous system or brain metastases * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study * Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0 * Pregnant (positive pregnancy test) or lactating * Urine protein:creatinine ratio > equal to 1.0 at screening * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess * Serious, non-healing wound, ulcer, or bone fracture * Diagnosis of any other malignancy except non-melanomatous skin cancer in the past 5 years. * Inability to comply with study and/or follow-up procedures

Study Objectives The aim of this study is to investigate the safety and metabolic-hormonal efficiency of supplementation vitamin D deficient/insufficient PCOS women with (calcium +vitamin D + metformin) for 8 weeks compared to (placebo+ metformin). Conditions: Polycystic Ovary Syndrome, Vitamin D Deficiency/Insufficiency Intervention / Treatment: DIETARY_SUPPLEMENT: Vitamin D3, DIETARY_SUPPLEMENT: Calcium Carbonate, DRUG: Metformin, DRUG: Placebo Location: Syrian Arab Republic Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * PCOS women aged 18-30 years diagnosed according to the Rotterdam criteria. * Vitamin D deficiency or insufficiency according to the Endocrine Society Clinical Practice Guideline. * Normal liver function. * Normal kidney function. Exclusion Criteria: * Pregnant, postpartum or breastfeeding women. * Females aged <18 or >30 years old. * Patients who were diagnosed with androgen-secreting tumours, Cushing's syndrome, congenital adrenal hyperplasia, hyperprolactinemia, hypercalcemia, malabsorption disorders, diabetes mellitus, thyroid disorders, liver disease, renal disease, epilepsy, cardiovascular disease. * History of kidney stones. * Usage of any hormonal therapy, corticosteroids (other than topical corticosteroids forms), insulin sensitizers, hypolipidemic agents, anti-obesity medications, vitamin D or calcium supplements, anti-epileptic drugs, or any other drugs known to affect endocrine parameters, carbohydrate metabolism, or calciotropic hormone concentrations during the last 3 months.

Study Objectives RATIONALE: Photodynamic therapy uses a drug that becomes active when it is exposed to a certain kind of light. When the drug is active, cancer cells are killed. Photodynamic therapy using methyl-5-aminolevulinate hydrochloride cream may be effective against skin cancer. PURPOSE: This phase I trial is studying the side effects and best dose of photodynamic therapy with methyl-5-aminolevulinate hydrochloride cream in determining pain threshold patients with skin cancer Conditions: Basal Cell Carcinoma of the Skin, Pain, Recurrent Skin Cancer Intervention / Treatment: DRUG: methyl-5-aminolevulinate hydrochloride cream, DRUG: photodynamic therapy, PROCEDURE: laser therapy Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patients with 1-2 superficial basal cell carcinoma (sBCC), 0.5 to 2 cm in diameter * Primary or recurrent lesions may be treated * Diagnosis must be confirmed by biopsy, at least 2 weeks pre treatment * Each patient with < 8 lesions can contribute a maximum of 2 lesions per treatment session, 1 lesion per light source, which can be treated the same day as permitted by scheduling; the remaining lesions may be treated as soon as scheduling permits with non protocol Photodynamic Therapy * Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: * Patients not meeting the above selection criteria * Lesions which are not suitable for diagnostic measurements * Patients with >= 8 lesions to be treated * Carcinomas of types known to have uncertain clinical margins (e.g. morpheaform or infiltrating), or any lesion felt to require Mohs surgery for definitive control * Lesions over boney prominences * Patients with porphyrias or known hypersensitivity to porphyrins * Patients with known photosensitivity diseases * Patients with allergies to Metvixia (MAL) cream ingredients (peanut and almond oil) * Patients previously treated with a systemic photo sensitizer within 4 months * Pregnant or nursing female patients * Patients unwilling or unable to follow protocol requirements * Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug

Study Objectives Polycystic ovary syndrome (PCOS) is a common endocrine disorder, with a prevalence of 5% to 15% in premenopausal women. Patients with PCOS presents as abnormal menstruation, ovulation disorders and/or hyperandrogenemia, and often accompanied by insulin resistance and other metabolic abnormalities. Metformin has been clarified as an option in patients with PCOS. However, the clinical responses to metformin are limited and different. Sodium glucose co-transporter 2 (SGLT2) inhibitors are novel drugs for the treatment of type 2 diabetes, with weight loss, reducing insulin resistance and cardiovascular benefits. Limited data is available on the efficacy of SGLT2 inhibitors in patients with PCOS. Conditions: Polycystic Ovary Syndrome Intervention / Treatment: DRUG: SGLT2 inhibitors, DRUG: Metformin Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion criteria: * Fmale aged 18- 45; * Meet Rotterdam criteria; * Insulin Rsistance Exclusion Criteria: * Women who are pregnant or have a pregnancy plan within six months; ·Congenital adrenocortical hyperplasia; * Hyperprolactinemia; * Hyperthyroidism or hypothyroidism; * Abnormal liver function (>= 3 times of the upper limit of normal range); * Abnormal renal function (GFR<60ml/min/1.73m2); * Adrenal or ovarian tumors secreting androgens; * Used contraceptives, metformin, GLP-1RA, SGLT2I, pioglitazone and contraceptives in the last 3 month.

Study Objectives Phase I: The goal of this clinical research study is to find the highest dose of estramustine phosphate administered intravenously in combination with a fixed dose of Taxol (paclitaxel) that can be given safely to participants with prostate cancer who have failed to further benefit from hormone treatment. Phase II: The goal of this clinical research study is to find out if the combination of the drugs estramustine phosphate and paclitaxel will shrink or control prostate cancer that has not responded to hormone treatment. A second goal is to find out if the side effects of these drugs can be reversed. The safety of these drugs will also be studied. Conditions: Prostate Cancer Intervention / Treatment: DRUG: Estramustine, DRUG: Taxol Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with histologic proof of adenocarcinoma of the prostate and must have failed conventional hormonal therapy. * Patients must have osteoblastic bone metastases. At least one osteoblastic lesion must be documented by plain film. Patients with mixed or osteolytic bone metastases must have a biopsy to exclude histologic variants of prostate cancer or metastasis from another primary (for phase II only). * Patients must have evidence of progression of disease as demonstrated by 2 consecutive rise in PSA (an absolute change of at least 1 ng/mL) over 4 weeks. * Patients on flutamide, nilutamide, or bicalutamide should be discontinued from flutamide or nilutamide and bicalutamide for at least 4 weeks and 8 weeks, respectively. * Patients must have an expected survival of at least three months and a Zubrod performance status of < 2 (Zubrod scale; Appendix B). * Patients may receive no concurrent chemotherapy or immunotherapy. * Patients must have castrate serum testosterone levels (< 30 ng/dl). For patients who are medically castrated, lutenizing hormone releasing hormone analog must continue to maintain testicular suppression. * Patients must have adequate bone marrow function defined as an absolute peripheral granulocyte count of > 1,500/mm3 and platelet count of > 100,000/mm3; adequate hepatic function defined with a bilirubin of < 1.5 mg% and SGOT (AST) < 2X the upper limits of normal; adequate renal function defined as serum creatinine clearance > 40 cc/min (measured or calculated). * Patients must be >= 18 years old. * Patients may have received oral EMP or no more than one cytotoxic therapy. * Patients must sign a written informed consent form prior to treatment. Exclusion Criteria: * Patients with severe intercurrent infection. * Patients with prior exposure to Taxol. * Patients whose tumors contain small cell or sarcomatoid elements. * Patients with evidence of conduction block or active myocardial ischemia on ECG. * Patients with a history of prior malignancy (except noninvasive cutaneous carcinoma). * Patients with a history of thromboembolism.

Study Objectives Percutaneous sclerotherapy is currently a widely used treatment for subcutaneous low-flow vascular malformations. Considered as a low-flow vascular malformation, symptomatic liver hemangiomas could also theoretically be safely and effectively treated by percutaneous sclerotherapy with a mixture of Bleomycin and Lipiodol. The safety and efficacy of percutaneous sclerotherapy was firstly introduced by the investigator's investigators in 5 patients in a pilot study. The aim of this study is to design and conduct a study to evaluate the safety and efficacy of percutaneous sclerotherapy in a larger sample size with a long term follow-up. Conditions: Hemangioma Liver Intervention / Treatment: PROCEDURE: sclerotherapy arm Location: Iran, Islamic Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * patients with symptomatic liver hemangioma Exclusion Criteria: * hepatic or renal impairment * abdominal symptoms unrelated to a liver mass * uncorrectable coagulopathy * lung fibrosis * allergy to contrast media * systemic infection * liver abscess * biliary obstruction

Study Objectives This is a randomized phase II study comprising of two treatment arms in patients who are previously untreated for metastatic or recurrent colorectal cancer. Conditions: Metastatic Colorectal Cancer Intervention / Treatment: DRUG: Chemotherapy Location: Hong Kong Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Age >= 18 years. * ECOG performance status of 0-2. * Histological proof of adenocarcinoma of colon or rectum with evidence of metastatic disease. * At least one unidimensionally measurable lesion with a diameter >20 mm using conventional CT or MRI scans, or > 10 mm with spiral CT * No prior drug treatment or chemotherapy for metastatic disease. * No prior HER2 or EGFR inhibitors. No prior Oxaliplatin in any clinical setting. * Absolute granulocyte count > 1.5 x 109/L, platelet count > 100 x 109/L, hemoglobin level > 9.0 g/L, INR < 1.5. * Adequate renal & hepatic functions: serum creatinine < 1.5 x upper limit of normal (ULN) or calculated creatinine clearance > 50ml/min, serum bilirubin < 1.5 x ULN, ALT < 2.5 x ULN or < 5 x ULN in case of liver metastases, albumin level > 30g/dL). * Prior adjuvant or neoadjuvant chemotherapy for non-metastatic CRC is allowed if > 3 months has elapsed since the last dose of chemotherapy. * Prior open surgery is allowed if > 28 days* has elapsed since the date of surgery, wound healing is satisfactory and recovery from any complications from the surgery is adequate. (*For laparoscopic surgery, > 14 days from the date of surgery). * No serious medical conditions such as myocardial infarction within 6 months prior to entry, or any other medical conditions that might be aggravated by treatment Exclusion Criteria: * Prior history of any malignancies, except basal cell cancer of skin, cervical CIN. * Treatment with radiotherapy < 30 days. * Pregnant or lactating females * Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study. * Patients who have not recovered from surgery or other medical illness such as infection. * Evidence of central nervous system disease. Patients with a history of uncontrolled seizures, central nervous disorders or psychiatric disability judged by the investigator to be clinically significant precluding informed consent or interfering with compliance for oral drug intake should be excluded from the study * Patients lacking physical integrity of upper gastrointestinal tract or malabsorption syndrome or unable to swallow tablets. * Prior unanticipated severe reaction to fluoropyrimidine therapy (with or without documented DPD deficiency). * Interstitial pneumonia or extensive symptomatic fibrosis of the lungs. * Requirement for concurrent use of the antiviral agent sorivudine (antiviral) or chemically related analogues, such as brivudine. * Known peripheral neuropathy >= NCI CTC grade 1. * Current or recent (within 10 days prior to study treatment start) use of full-dose oral anticoagulant (e.g. warfarin) or thrombolytic agent.

Study Objectives The purpose of this study is to evaluate the safety and effectiveness of the bevacizumab and capecitabine combination in frail patients with untreated metastatic colorectal cancer. Conditions: Colorectal Cancer Intervention / Treatment: DRUG: Capecitabine (Xeloda), DRUG: Bevacizumab Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically or cytologically proven adenocarcinoma of the colon at first diagnosis * Stage IV disease, with at least one measurable lesion according to the RECIST criteria * Eastern Cooperative Oncology Group (ECOG) performance status 2 * No prior chemotherapy for metastatic colorectal cancer * Prior adjuvant chemotherapy is permitted. * At least 28 days since prior surgery * If female of childbearing potential, pregnancy test is negative and willing to use effective contraception while on treatment and for at least 3 months thereafter. * Required laboratory values: * Absolute neutrophil count > 1.5 x 10^9/L * Hemoglobin > 9.0 g/dL * Platelet count > 100 x 10^9/L * Creatinine < 2.0 mg/dL * Total bilirubin < 1.5 x upper limit of normal (ULN) (Patients with documented Gilbert's syndrome are eligible.) * Alkaline phosphatase and AST/ALT within the following parameters. In determining eligibility, the more abnormal of the two values (AST or ALT) should be used: * Alkaline phosphate and AST/ALT < or = ULN * Alkaline phosphate > 1x but < or = 2.5x and AST/ALT < or = ULN * Alkaline phosphate > 2.5x but < or = 5x and AST/ALT < or = ULN * Alkaline phosphate < or = ULN and AST/ALT > 1x but < or = 1.5x * Alkaline phosphate > 1x but < or = 2.5 x and AST/ALT > 1x but < or = 1.5x * Alkaline phosphate < or = ULN and AST/ALT > 1x but < or = 2.5x Exclusion Criteria: * Prior chemotherapy for metastatic colorectal cancer * Prior treatment with an anti-angiogenic agent * Concurrent therapy with any other non-protocol anti-cancer therapy * Current or prior history of central nervous system or brain metastases * Presence of neuropathy > grade 2 (NCI-Common Toxicity Criteria (CTC) version 3.0) at baseline * Presence of any non-healing wound, fracture, or ulcer, or the presence of clinically significant (> grade 2) peripheral vascular disease * History of any other malignancy within the past 5 years, with the exception of non-melanoma skin cancer or carcinoma-in-situ of the cervix * Clinically significant cardiovascular disease (e.g., blood pressure [BP] > 150/100, myocardial infarction or stroke within the past 6 months, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication * Active peptic ulcer disease, inflammatory bowel disease, or other gastrointestinal condition increasing the risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning therapy * Active infection requiring parenteral antimicrobials * The presence of any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of the drugs in this protocol or place the subject at undue risk for treatment complications * Inability to comply with the study protocol or follow-up procedures * Pregnancy or lactation * A history of a severe hypersensitivity reaction to bevacizumab, or capecitabine or other drugs formulated with polysorbate 80. * Evidence of bleeding diathesis or coagulopathy. * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of the need for a major surgical procedure during the course of the study; minor surgical procedure, fine needle aspiration or core biopsy within 7 days prior to Day 0 * Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study * Unstable angina * Urine protein creatinine ratio greater than or equal to 1. * Therapeutic anticoagulation with oral anticoagulation medications, specifically coumarins

Study Objectives This is a placebo controlled trial investigating the effect of 6 months atorvastatin 20mg/day therapy on androgens, glucose metabolism and inflammatory markers in women with PCOS. We assume that during 6 months atorvastatin therapy a significant improvement in hyperandrogenism, glucose metabolism and inflammatory markers is observed. Conditions: Polycystic Ovary Syndrome Intervention / Treatment: DRUG: Atorvastatin, DRUG: Placebo Location: Finland Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: SINGLE_GROUP Masking: DOUBLE

Inclusion Criteria: * diagnosed for PCOS (Rotterdam criteria) * aged 30-50 years * safe non-hormonal contraception Exclusion Criteria: * use of cholesterol lowering agents * use of antidepressants * use of cortisone medication (p.o.) * use of hormonal contraception * nursing * pregnancy * DM-T2 * liver disease * menopause * kidney or liver failure

Study Objectives The purposes of this study are: 1. To find the highest dose of monthly intravenous Zometa that can be given with daily low doses of cyclophosphamide by mouth to children with recurrent or refractory neuroblastoma without causing severe side effects. 2. To find out the side effects seen by giving Zometa and cyclophosphamide on this schedule at different dose levels. 3. To measure blood and urine levels of Zometa during treatment 4. To preliminarily evaluate the antitumor activity of Zometa and concomitant oral cyclophosphamide in children with recurrent and/or refractory neuroblastoma within the confines of a Phase I study. 5. To measure the effects of Zometa on markers of bone breakdown found in urine, blood, and bone marrow 6. To measure the effects of Zometa on the immune system. Conditions: NEUROBLASTOMA Intervention / Treatment: DRUG: Zolendric acid, DRUG: Cyclophosphamide 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: * Less than or equal to 30 years of age when enrolled on study. * A diagnosis of neuroblastoma either by histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines. * High-risk neuroblastoma with at least ONE of the following: 1. Recurrent/progressive disease. 2. Refractory disease (i.e. less than a partial response to frontline therapy). No biopsy is required for eligibility for study. 3. Persistent disease after at least a partial response to frontline therapy (i.e. patient has had at least a partial response to frontline therapy but still has residual disease by MIBG, CT/MRI, or bone marrow). Patients in this category are REQUIRED to have a biopsy of at least one residual site demonstrating viable neuroblastoma. * Bone disease demonstrated by uptake on MIBG scan. If the patient's tumor is known to be non-avid for MIBG then the patient must have evidence of either new lesions or progression of prior lesions on bone scan or plain radiographs. * A Karnofsky or Lansky performance status of greater than or equal to 50%. Patients who are unable to walk because of paralysis or tumor pain, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. * Life expectancy of greater than 2 months. * Fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. 1. Must not have received within 3 weeks of entry onto this study (4 weeks if prior nitrosourea). 2. Patients must not have received radiation for a minimum of four weeks prior to study entry at the site of any lesion that was biopsied to document study eligibility. A minimum of six weeks is required following prior large field radiation therapy (ie: TBI, craniospinal therapy, whole abdomen, total lung, or over 50% marrow space). 3. Patients must not have had an autologous stem cell transplant within 3 months of entry onto this study. Patients status post-allogeneic stem cell transplant are excluded. 4. A minimum of six weeks is required following prior therapeutic doses of MIBG. 5. Must not have received factors that support platelet or white cell number or function within 7 days of study entry. 6 Must not have received bisphosphonate therapy. * Must not be receiving any other anti-cancer agents or radiotherapy at the time of study entry or while on study. * Organ Function Requirements Adequate Bone Marrow Function: a. ANC greater than or equal to 750 b. Platelet count greater than or equal to 50,000, transfusion independent (defined as no platelet transfusion for one week). NOTE: hematologic criteria must be met by all patients, regardless of neuroblastoma involvement in bone marrow. Adequate Renal Function a. Glomerular Filtration Rate of greater than or equal to 70 ml/min/1.73 m2, OR b. Age-adjusted normal serum creatinine for age Adequate Liver Function a. Total bilirubin less than or equal to 1.5 x normal for age, and b. SGPT (ALT) and SGOT (AST) less than 5 x normal for age. * Ionized serum calcium greater than or equal to 1.0 mmol/L (Patients are allowed to be on calcium supplements if serum calcium is stable) * Urinalysis with less than or equal to 1+ heme. * Reproductive Function: Negative serum beta-HCG in females and use of effective contraception in females and males of child-bearing potential. Exclusion Criteria: * Status post-ALLOGENEIC stem cell transplant. * Received prior bisphosphonate therapy. * Receiving other investigational agents. * Have an uncontrolled infection. * Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study. * Pregnancy or breast feeding.

Study Objectives This Phase II research project will test the efficacy, safety, and tolerability of an experimental drug combination: either nivolumab and BBI608 or nivolumab and BNC105 in patients with metastatic colorectal cancer who have previously failed standard of care treatment. Conditions: Colorectal Cancer Metastatic Intervention / Treatment: DRUG: Nivolumab 10 MG/ML, DRUG: BNC 105, DRUG: BBI608 Location: Australia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patient has a histological diagnosis of adenocarcinoma of colorectal origin. * Has documented microsatellite stable tumour as assessed by PCR or IHC. * Metastatic disease that is not resectable. * Male or female patients > 18 years of age at screening. * Failed in any sequence or combination oxaliplatin, fluoropyrimidine, irinotecan with or without bevacizumab where failure is defined as progression or toxicity precluding further therapy. * For patients with ras/b-raf wild type tumours: failed anti EGFR therapy (cetuximab and/or panitumumab) where failure is defined as progression or toxicity precluding further therapy. Patients with b-raf mutant tumours and/or right sided primary tumours may have received anti-EGFR therapy but this is not mandated. * Patient has measurable disease according to RECIST 1.1. * Metastatic lesion(s) amenable to biopsy, this cannot be the sole site of measurable disease. * ECOG performance status 0 or 1. * Adequate organ and hematologic function within 7 days of randomisation, defined by: 1. Neutrophils > 1.5 X 109/L 2. Platelets > 80 X 109/L 3. Serum aspartate transaminase (AST) or alanine transaminase (ALT) < 3 x upper limit of normal (ULN) 4. Bilirubin < 1.5 x ULN 5. Albumin >30g/L 6. Creatinine clearance >= 50ml/min(Cockcroft-Gault). * Life expectancy of at least 12 weeks * No other concurrent uncontrolled medical conditions * No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other cancer treated with curative intent >2 years previously without evidence of relapse. * Female patients of childbearing potential should have a negative urine or serum pregnancy within 24 hours prior to randomisation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Female patients of childbearing potential should be willing to use a reliable method of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 180 days after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. * Male patients with female partners of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy. * Patient has provided written informed consent including consent for tumour biopsies and donation of tumour tissue for biomarker studies. Exclusion Criteria: * Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol. * Patients with any active, known, or suspected autoimmune disease, with the following exceptions: 1. Patients with vitiligo, type 1 diabetes mellitus, resolved childhood asthma or atopy are permitted to enroll. 2. Patients with suspected autoimmune thyroid disorders may be enrolled if they are currently euthyroid or with residual hypothyroidism requiring only hormone replacement. 3. Patients with psoriasis requiring systemic therapy must be excluded from enrolment * Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg/day prednisone equivalent) or other immunosuppressive medications within 14 days of randomisation. Inhaled or topical steroids and adrenal replacement doses > 10mg/day prednisone equivalents are permitted in the absence of active autoimmune disease. * Patient has evidence of interstitial lung disease or active, non-infectious pneumonitis. * Has an active infection requiring systemic therapy. * Patients receiving long-term anti-coagulation or anti-platelet agents which cannot be ceased for an appropriate interval to allow mandatory tumour biopsies prior to and during therapy. * Patient has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate. * Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). * Has a known history of HIV (HIV 1/2 antibodies). Formal testing is only required if there is significant clinical suspicion of HIV. * Known active brain metastases (unless adequately treated with surgery and/or radiotherapy >30 d prior and asymptomatic). * Significant vascular events within the previous 6 months (unstable angina, myocardial infarction, TIA, CVA).

Study Objectives Determine the value of the initial measurement of the hemoglobin content of reticulocytes (RET-He) for predicting the response to martial treatment for patients with a solid tumor with a functional martial deficiency as defined NCCN2016 (with or without inflammation). The aim is to refine the current definition of functional martial deficiency in order to best adapt the iron prescription in oncology by giving iron only if necessary, i.e. if the RET is low. Conditions: Solid Tumor, Adult, Anemia Deficiency Intervention / Treatment: BIOLOGICAL: Haemoglobin measure Location: France Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Age >= 18 years. * Metastatic solid tumor or not. * Anemia by functional martial deficiency (as defined in the NCCN2016 recommendations): o Hb < 11 g/DL, TSAT < 20% and ferritinlike between 30 and 800 ng/ml * Initial assessment of anemia carried out at the laboratory of Biopathology of the ICO Exclusion Criteria: * Patient with malignant hemopathy. * Patient with chronic renal failure with an estimation of renal filtration rate according to the formula CKD-EPI < 60 ml/min/1.73 m². * Patient with vitamin B12 deficiency, folate deficiency, hemolysis and/or hemoglobinopathy. * Patient with active infection. * Patient with bone marrow tumor. Confirmation by a osteo-medullary biopsy (BOM) or a myelogram is not necessary to exclude the patient. * Patient who received ASE within two months prior to the initial blood test. * Patient who received iron (oral or injectable) in the two months preceding the initial blood test. * Patient who received a transfusion of globular pellets in the month preceding the initial blood test.

Study Objectives This is a pilot vaccine study in adults with recurrent WHO Grade II gliomas. The purpose of this study is to test the safety and efficacy of an experimental tumor vaccine made from peptides in combination with the study drug Poly-ICLC. Poly-ICLC, manufactured by Oncovir, Inc., has already been received and is generally well tolerated by subjects in earlier studies and has been shown to decrease the size of brain tumors in some cases. The immunological and safety data will be used to decide whether a larger study of clinical efficacy is warranted. Conditions: Astrocytoma, Oligoastrocytoma, Oligodendroglioma Intervention / Treatment: BIOLOGICAL: Peptide vaccine + Poly-ICLC Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: EARLY_PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Participants must have recurrent supratentorial WHO grade II astrocytoma, oligoastrocytoma or oligodendroglioma that is histologically confirmed either by the previous biopsy or resection, or at the time of re-operation (re-operation before entry to the current study is allowed; however post-surgery Decadron must be off for at least 4 weeks before administration of the first vaccine). Patients may have received prior external beam radiotherapy and/or chemotherapy. With regard to the prior therapy, patients may have had treatment for no more than 2 prior relapses. Relapse is defined as progression following initial therapy (i.e. radiation +/- chemo if that was used as initial therapy). The intent therefore is that patients may have had 3 prior therapies (initial therapy and treatment for 2 relapses). If the patient had a surgical resection for relapsed disease, and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered as 1 relapse. * HLA-A2 positive based on flow cytometry. * Tumor recurrence is defined by the increase of maximum tumor diameter, based on the axial and/or coronal T2 or FLAIR MR images. Increase of tumor size can be based on comparison with previous scans performed up to prior 3 years to allow assessment of slow-growth of the tumor. * Patients must have recovered from the toxic effects of prior therapy: 4 weeks from any investigational agent, 4 weeks from prior cytotoxic therapy and/or at least two weeks from vincristine, 4 weeks from nitrosoureas, 3 weeks from procarbazine administration, and 1 week for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count). Any questions related to the definition of non-cytotoxic agents should be directed to the Principal Investigator. With regard to previous RT, there must be at least 6 months from the completion of RT (or radiosurgery). * Participants must be at least 18 years old. For patients under 18 years old, we have a separate, but similar vaccine study through the Children's Hospital in Pittsburgh. * All participants must sign an informed consent document. * Participants must have a Karnofsky performance status of > 60 (Appendix I). * Documented negative serum HCG for female participants of child-bearing age. Males and females must agree, in the consent form, to use effective birth control methods during the course of vaccination. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the peptide-based vaccine and poly-ICLC, breastfeeding should be discontinued if the mother is treated in this study. * Participants must be free of systemic infection. * Participants with adequate organ function as measured by white blood count >= 2500/mm3; lymphocytes >= 800/mm3; platelets >= 100,000/mm3, hemoglobin >= 10.0 g/dL, AST, ALT, GGT, LDH, alkaline phosphatase within 2.5 x upper normal limit, and total bilirubin <= 2.0 mg/dL, and serum creatinine within 1.5 X upper limit of normal limit. Coagulation tests PT and PTT have to be within normal limits. Exclusion Criteria: * Presence of gliomatosis cerebri, cranial or spinal leptomeningeal metastatic disease. * Even if the initial diagnosis was WHO grade II glioma, if the pathological diagnosis for the recurrent disease demonstrate transformation to higher grade (i.e. WHO grade III or IV) gliomas, patients will be excluded from the eligibility. * Concurrent treatment or medications including: * Radiation therapy * Chemotherapy * Interferon * Allergy desensitization injections * Growth factors * Interleukins * Any investigational therapeutic medication * Participants must not have had prior autoimmune disorders requiring cytotoxic or immunosuppressive therapy, or autoimmune disorders with visceral involvement. Participants with an active autoimmune disorder requiring these therapies are also excluded. Mild arthritis requiring NSAID medications will not be exclusionary. * Use of immunosuppressives within 4 weeks prior to study entry or anticipated use of immunosuppressive agents. Dexamethasone, or other corticosteroid medications, if used peri-operative period and/or during radiotherapy, must be tapered and discontinued at least 4 weeks before administration of the first vaccine. Topical corticosteroids and Inhaled steroids are acceptable. * Participants who have another cancer diagnosis, except that the following diagnoses will be allowed: * squamous cell cancer of the skin without known metastasis * basal cell cancer of the skin without known metastasis * carcinoma in situ of the breast (DCIS or LCIS) * carcinoma in situ of the cervix * any cancer without distant metastasis that has been treated successfully, without evidence of recurrence or metastasis for over 5 years * Participants with known addiction to alcohol or illicit drugs. * Because patients with immune deficiency are not expected to respond to this therapy, HIV-positive patients are excluded from the study. * Patients who previously participated in UPCI 07-057 are excluded.

Study Objectives Primary objective of the study's Safety run-in: - To determine the maximum tolerated dose (MTD) of cilengitide in combination with cetuximab, and platinum-based chemotherapy (cisplatin/vinorelbine or cisplatin/gemcitabine). Primary objective of the study's Randomization Part: - To assess the efficacy of cilengitide in combination with cetuximab and platinum-based chemotherapy (cisplatin/vinorelbine or cisplatin/gemcitabine) compared to cetuximab and platinum-based chemotherapy alone in terms of progression-free survival (PFS) time. Study design and plan: This is a multicenter, open-label, randomized, controlled Phase II study with a safety run-in part in subjects with advanced non-small cell lung cancer (NSCLC). During the safety run-in, the regimen was intensified stepwise by cohort (cilengitide intravenous \[i.v.\] 1000 milligram \[mg\] to 2000 mg twice a week) in a classical 3+3 subjects (for each platinum-based chemotherapy regimens separately) approach with predefined dose- and schedule reduction rules. In the safety run-in 12 subjects were included and evaluated for safety and feasibility of different escalating doses of cilengitide administered twice weekly in combination with cetuximab, cisplatin and vinorelbine or gemcitabine. After completion of the safety run-in, the randomized part will be started, during which all subjects will receive cetuximab and platinum-based chemotherapy (cisplatin/vinorelbine or cisplatin/gemcitabine). Subjects will be centrally randomized on a 1:1 basis to either Group A or C; Group B will be closed with implementation of Amendment No. 4 (dated 20 December 2010): • Group A: Cilengitide 2000 mg once weekly (Days 1, 8, and 15 of every 3-week chemotherapy cycle) in combination with cetuximab and platinum-based chemotherapy that will consist of the following: * Cetuximab once weekly (Days 1, 8, and 15), plus cisplatin on Day 1 and vinorelbine on Days 1 and 8 of every 3-week chemotherapy cycle, or * Cetuximab once weekly (Days 1, 8, and 15), plus cisplatin on Day 1 and gemcitabine on Days 1 and 8 of every 3-week chemotherapy cycle. The decision which of the 2 chemotherapy regimens will be applied for a given subject is at the discretion of the treating investigator. • Group B: Cilengitide 2000 mg twice weekly (Days 1, 4, 8, 11, 15, and 18 of every 3-week chemotherapy cycle) in combination with cetuximab and platinum-based chemotherapy as described for Group A. Group B will be closed with implementation of Amendment No. 4 (global, dated 20 December 2010). Subjects randomized to Group B before implementation of Amendment No 4 will continue to be treated as planned. • Group C: Cetuximab and platinum-based chemotherapy as described for Group A Chemotherapy will be given until radiographically documented progressive disease (PD) or unacceptable toxicity but for no more than 6 cycles. Cilengitide and cetuximab will be given until radiographically documented PD or unacceptable toxicity. Randomization will be performed centrally using an interactive voice/web response system (IXRS). A stratified block randomization procedure will be employed using chosen first-line chemotherapy (cisplatin/vinorelbine versus cisplatin/gemcitabine) as stratification criterion. Conditions: Carcinoma, Non-Small-Cell Lung Intervention / Treatment: DRUG: Cilengitide, DRUG: Cilengitide, DRUG: Cetuximab, DRUG: Cisplatin, DRUG: Cisplatin, DRUG: Gemcitabine, DRUG: Vinorelbine, DRUG: Cilengitide, DRUG: Cilengitide, DRUG: Cetuximab, DRUG: Chemotherapy Location: Germany, Czech Republic, Italy, Spain, Belgium, Ireland, France, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion criteria: * Written informed consent obtained before undergoing any study-related activities. * Male or female, at least 18 years of age * Histologically confirmed NSCLC, Stage IIIb with documented malignant pleural effusion or Stage IV (according to staging system 6th edition) * EGFR expression greater than or equal to (>=) 200 on tumor tissue determined by local testing using the kit and testing procedures described in the study Manual of Operations (MOP) * Archived tumor material sample for central histology and further biomarker research including mutational analysis of genes such as EGFR, k-ras, b-raf (material details described in the study MOP) * At least 1 radiographically documented measurable lesion in a previously non-irradiated area according to evaluation criteria in solid tumors (RECIST), i.e. this lesion must be adequately measurable in at least 1 dimension (longest diameter [LD] to be recorded) as >=2 centimeter (cm) by conventional techniques or >=1 cm by spiral CT scan * Eastern Cooperative Oncology Group (ECOG)-performance status 0-1 * Leukocyte count >=3.0 x 10^9 per liter (/L) * Absolute neutrophil count (ANC) >=1.5 x 10^9/L * Platelets >=100 x 10^9/L * Hemoglobin >=9 gram per deciliter (g/dL) (without transfusions) * Bilirubin less than or equal to (<=) 1.5 x upper limit of normality (ULN) * Aspartate Aminotransferase (AST) <=5 x ULN and Alanine Aminotransferase (ALT) <=5 x ULN * Serum creatinine <=1.25 x ULN and/or creatinine clearance >=60 milliliter per minute (mL/min) * Prothrombin time (PT), international normalized ratio (INR) within normal limits and partial thromboplastin time (PTT) below upper limit of normal. * Sodium and potassium within normal limits or <=10% above or below (supplementation permitted). * Effective contraception for both male and female subjects (if the risk of conception exists). If female, she must: be neither pregnant nor breast-feeding, nor attempting to conceive, use a highly effective method of contraception for at least 7 days before entry into the trial, throughout the entire duration of the trial and for 6 months following completion of the last dose of trial medication. A highly effective method of contraception is defined as those which result in a low failure rate (that is, <1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, intrauterine devices (IUDs) (hormonal or copper-based), sexual abstinence or vasectomized partner, or be post-menopausal or surgically sterilized. If male, he must be willing to use contraception to avoid pregnancies for at least 7 days before entry into the trial, throughout the entire duration of the trial and for 6 months following the last dose of trial medication. Two negative semen analyses post-vasectomy have to be available in order to be considered infertile Exclusion criteria: * Prior treatment with an antibody or molecule targeting EGFR- and/or vascular endothelial growth factor receptor (VEGFR)-related signaling pathways * Previous chemotherapy for NSCLC including prior adjuvant therapy * History of or current brain metastasis and/or leptomeningeal disease (known or suspected) * Radiotherapy (except localized radiotherapy for pain relief), major surgery or any intake of investigational drug in the 30 days before the start of study treatment entry * Concurrent chronic immunosuppressive or hormone anti-cancer therapy (physiologic hormone replacement or corticosteroid treatment for chronic obstructive pulmonary disease [COPD] is allowed) * Clinically relevant coronary artery disease (New York Heart Association [NYHA] functional angina classification III/IV), congestive heart failure (NYHA III/IV), clinically relevant cardiomyopathy, history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia * History of coagulation disorder associated with bleeding, recurrent or recent thrombotic events or history of hemoptysis related to bronchopulmonary cancer. Hemoptysis is defined as coughing more than a teaspoon of red blood per day * Recent peptic ulcer disease (endoscopically proven gastric, duodenal or esophageal ulcer) within 6 months of study treatment start * Presence of any contra-indication to treatment with cilengitide, cetuximab, cisplatin and vinorelbine or gemcitabine including: * Known hypersensitivity to cilengitide, cetuximab, cisplatin, vinorelbine, or gemcitabine or to any of the excipients of these drugs * Superior vena cava syndrome contra-indicating hydration * Symptomatic peripheral neuropathy National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=2 and/or ototoxicity NCI CTC AE Grade >=2, except if due to trauma or mechanical impairment due to tumor mass * Phenytoin (introduced to prevent the anticonvulsant effect of certain anticancer drugs) (contra-indication for cisplatin) * Yellow Fever Vaccine, Live Attenuated Vaccines (contra-indications for cisplatin) * Pregnancy or lactation period * Concurrent treatment with a non-permitted drug * Treatment with any other investigational product within the past 30 days * Previous malignancy other than NSCLC in the last 5 years except for basal cell cancer of the skin or pre-invasive cancer of the cervix * Medical or psychological conditions that would not permit the subject to complete the study or sign informed consent * Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such * Patients with hepatitis, massive liver metastases (>75%), current alcoholism or liver cirrhosis (because of vinorelbine and gemcitabine) * Patients who have been therapeutically anticoagulated * Legal incapacity or limited legal capacity * Significant disease (for example, interstitial lung disease) which, in the investigator's opinion, would exclude the subject from the study

Study Objectives This was a Phase 2, open-label, multicenter study evaluating the preliminary efficacy and safety of venetoclax (ABT-199) administered orally in participants with acute myelogenous leukemia (AML). Conditions: Acute Myelogenous Leukemia, AML, Acute Myeloid Leukemia Intervention / Treatment: DRUG: ABT-199 Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histological or cytological confirmation of relapsed or refractory acute myelogenous leukemia (AML) (by World Health Organization [WHO] classification) or untreated AML in participants who are unfit for intensive therapy. * Participant has an Eastern Cooperative Oncology Group (ECOG) Performance score of 0 to 2. * Participant must have adequate renal function as demonstrated by a calculated creatinine clearance >= 50 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula using ideal body mass (IBM) instead of mass. * Participant must have adequate liver function as demonstrated by: * aspartate aminotransferase (AST) <= 3.0 × upper limit of normal (ULN)* * alanine aminotransferase (ALT) <= 3.0 × ULN* * bilirubin <= 1.5 × ULN* *unless considered due to leukemic organ involvement. (Participants with Gilbert's Syndrome may have had a bilirubin > 1.5 × ULN per discussion between the investigator and AbbVie medical monitor) Exclusion Criteria: * Participant has received acute anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal or any investigational therapy within 14 days or 5 half-lives (whichever is shorter) prior to first dose of ABT-199. * Participant has received a monoclonal antibody for anti-neoplastic intent within 8 weeks prior to the first dose of study drug. * Participant has received potent Cytochrome P450, family 3, subfamily A (CYP3A) inducers (such as rifampin, carbamazepine, phenytoin and St. John's wort) and warfarin or requires the use of warfarin (due to potential drug-drug interactions that may potentially increase the exposure of warfarin and complications of this effect) within 7 days prior to the first dose of study drug. * Participant has received CYP3A inhibitors (such as fluconazole, ketoconazole, and clarithromycin) within 5 days prior to the first dose of study drug. * Participant has a white blood cell count > 25 x 10^9/L. * Participant has acute promyelocytic leukemia (French-American-British Class M3 AML). * Participants with known active central nervous system (CNS) disease.

Study Objectives The purpose of this study is to find what effects, good and/or bad, treatment with two drugs has on leukemia. The first medicine is tretinoin (also called all-trans retinoic acid, ATRA, or Vesanoid). It is an approved medicine that causes the leukemia cells in APL to mature. It is related to vitamin A. The second is arsenic trioxide (Trisenox). It is an approved medicine for APL that comes back after earlier treatment. APL is most often treated with tretinoin and standard chemotherapy drugs. These chemotherapy drugs can cause infection and bleeding. They can also damage the heart and normal bone marrow cells. This can lead to a second leukemia years later. In this study, the investigators are using tretinoin and arsenic trioxide together. Both drugs work to treat APL. They have been used together in only a limited number of people. The investigators want to use these drugs together to reduce the amount of standard chemotherapy and decrease side effects. The patient will receive standard chemotherapy with a drug called idarubicin only if they have a higher chance of the leukemia coming back or a higher risk of side effects. Conditions: Acute Promyelocytic Leukemia Intervention / Treatment: DRUG: Tretinoin and Arsenic Trioxide Location: United States, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Previously untreated patients with a morphologic diagnosis of APL, confirmed by demonstration of t(15;17) using conventional cytogenetics OR florescence in situ hybridization (FISH), OR a positive RT-PCR assay for PML-RAR at the subject's local institution. * Age >=18 years. Karnofsky performance status of >= 60%. * Adequate renal function as demonstrated by a serum creatinine <= 2.0 mg/dl or a creatinine clearance of > 60 ml/min. * Adequate hepatic function as demonstrated by a bilirubin < 2.0 mg/dl (unless attributable to Gilbert's disease) and an alkaline phosphatase, AST, and ALT <= 2.5 times the upper limit of normal. * Normal cardiac function as demonstrated by a left ventricular ejection fraction >= 50% on echocardiogram or MUGA scan. * QTc <= 500 msec on baseline ECG. * Negative serum pregnancy test in women of childbearing potential. * Ability to swallow oral medication. * Men and women of child-bearing potential must be willing to practice an effective method of birth control during treatment and at least 4 months after treatment is finished. * Patients with central nervous system involvement by APL are eligible and may receive concomitant treatment with radiation therapy and/or intrathecal chemotherapy in accordance with standard medical practice. Exclusion Criteria: * Previous treatment for APL, except tretinoin, which may be given for up to 7 days prior to study entry. * Active serious infections not controlled by antibiotics. * Pregnant women or women who are breast-feeding. * Concurrent active malignancy requiring immediate therapy. * Clinically significant cardiac disease (NY Heart Association Class III or IV), including chronic arrhythmias, or pulmonary disease. * Other serious or life-threatening conditions deemed unacceptable by the principal investigator.

Study Objectives Investigators propose to assess,the safety and tolerability profile (number of participants with adverse events) of bevacizumab (Avastin) when added to chemotherapy as front-line treatment of epithelial ovarian cancer, fallopian tube carcinoma or primary peritoneal carcinoma Conditions: Ovarian Cancer Location: Greece Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Written informed consent * Age >=18 years * Histologically confirmed advanced stage III (suboptimally debulked >1cm of residual disease) or stage IV ovarian cancer fallopian tube carcinoma or primary peritoneal cancer following surgical debulking with the aim of maximal surgical cytoreduction * One or more measurable lesions (>=1cm in diameter with spiral CT scan or >=2cm with conventional techniques) according to RECIST criteria * ECOG performance status <=2 * Adequate haematological, renal and hepatic function * Urine protein <2+ (dipstick) * Life expectancy of >12 weeks Exclusion Criteria: * Previous front line treatment for ovarina cancer * Previous radiotherapy to target lesions * Patients with brain metastases and/or cancerous meningitis * Presence or history of other neoplasm except properly treated basal cell skin cancer or in situ cervical carcinoma * Patients participating in interventional clinical trial

Study Objectives This single-arm study aims to assess the safety and tolerability profile of Fulvestrant(Faslodex®) as 2nd line and later therapy in postmenopausal women with locally advanced or metastatic breast cancer. The primary objective is to evaluate the adverse events after Fulvestrant (Faslodex®) for about 6 months Conditions: Locally Advanced or, Metastatic Breast Cancer Intervention / Treatment: DRUG: Fulvestrant Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: OTHER Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Post menopausal status women * Outpatient or inpatient with locally advanced or metastatic breast cancer who have failed with prior anti-estrogen therapy. * Estrogen receptor positive * Radiographic progression of disease after the prior therapy * Patients who agree to participate in this study and sign the informed consent Exclusion Criteria: * Patients who are treated with fulvestrant * Patients who are being treated with the other antitumor agents * Pregnancy or lactating women * History of hypersensitivity to any of included ingredients (eg. Castor oil) * Patients who are considered not fit for the study by investigators * Patients who have severe dysfunction of liver or kidney

Study Objectives The purpose of this study is to characterize the mass balance, absorption, metabolism, and elimination pathways of orally administered \[14C\] rucaparib followed by cycle by cycle treatment with rucaparib continuing until disease progression or other reason for discontinuation Conditions: Solid Tumor Intervention / Treatment: DRUG: C-14 labeled Rucaparib, DRUG: Rucaparib Location: Hungary Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: OTHER Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed advanced solid tumor * Part II only: Have a known deleterious BRCA1/2 mutation (germline or somatic) as determined by a local or central laboratory * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Adequate bone marrow, renal, and liver function Exclusion Criteria: * Prior treatment with chemotherapy, radiation, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, or angiogenesis inhibitors within 14 days prior to Day 1 * Participation in a trial involving administration of [14C]-labeled compound(s) within the last 6 months prior to Day 1 * Arterial or venous thrombi (including cerebrovascular accident), myocardial infarction, admission for unstable angina, cardiac angioplasty, or stenting within the last 3 months prior to Screening * Pre-existing duodenal stent, recent or existing bowel obstruction, and/or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib * Untreated or symptomatic central nervous system (CNS) metastases * Evidence or history of bleeding disorder * Participation in another investigational drug trial within 14 days prior to Day 1 (or 5 times the half-life of the drug, whichever is longer) or exposure to more than three new investigational agents within 12 months prior to Day 1 * Acute illness (eg, nausea, vomiting, fever, diarrhea) within 14 days prior to Day 1, unless mild in severity and approved by the Investigator and Sponsor's/designated medical representative * Active second malignancy

Study Objectives The study will evaluate the effects of BHQ880 in patients with previously untreated multiple myeloma and renal insufficiency who are not considered candidates for bisphosphonate therapy. The primary objective of the study will be to evaluate the effect of BHQ880 in combination with bortezomib and dexamethasone, compared to placebo administered with the combination on the time to first Skeletal Related Event (SRE) on study. Conditions: Multiple Myeloma, Renal Insufficiency Intervention / Treatment: DRUG: BHQ880, DRUG: BHQ880 Placebo, DRUG: bortezomib, DRUG: dexamethasone Location: United States, Spain, United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * Confirmed diagnosis of multiple myeloma * Life expectancy of more than 6 months in the absence of intervention * Must not have received previous or be receiving current antimyeloma therapies * Renal insufficiency * Recovered from the effects of any prior surgery or radiotherapy Exclusion Criteria: * Prior IV bisphosphonate therapy at any time or oral bisphosphonate therapy within 4 months of study entry * Paget's disease of bone or uncorrected hyperparathyroidism * Impaired cardiac function * Known HIV, known active hepatitis B, or known or suspected hepatitis C infection * Pregnant or nursing (lactating) women, * Women of child-bearing potential, UNLESS agreeable to using 2 birth control methods Other protocol-defined inclusion/exclusion criteria may apply

Study Objectives The purpose of this study is to develop new image analysis method using Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) for ovarian cancer. MRI is not currently part of the standard care for ovarian cancer. In this method, a contrast agent is used to make ovarian cancer visible during imaging. Conditions: Ovarian Cancer Intervention / Treatment: PROCEDURE: DCE-MRI scans Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Patients with measurable disease with evidence of at least one uni-dimensionally measurable tumor (> 1 cm) by CT or MRI scan according to RECIST (Response Evaluation Criteria in Solid Tumors) that the tumor has not been initially treated with surgery or radiation therapy. * Patients who will start treatment with bevacizumab combined with or without cytotoxic chemotherapy within 14 days from signing consent. Patients treated on an approved IRB therapeutic protocol for recurrent ovarian cancer with bevacizumab are eligible. * Patients with histologically confirmed ovarian epithelial cancer including primary peritoneal and fallopian tube adenocarcinoma. * 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 who are older than 21 years of age. * Patients who are able to understand and sign informed consent. Exclusion Criteria: * Patients treated on an approved IRB therapeutic protocol with a blinded arm of bevacizumab or placebo are not eligible (IRB 07-078 and IRB 05-138). * Patients with cardiac pacemakers. * Patients with certain prosthetic devices and implants who are not compatible with the high magnetic field present in the DCE-MRI scanners. * Patients who have experienced a prior adverse reaction to the gadolinium complex contrast agent used in DCE-MRI imaging and who don't meet criteria for creatinine and nephrogenic systemic sclerosis risk per guidelines of department of radiology. * Patients prone to claustrophobia. * Patients on dialysis.

Study Objectives The purpose of this study is to: * evaluate the activity of SAMITAL in reducing the incidence of severe mucositis in head-and-neck cancer patients undergoing chemo-radiotherapy. * assess tolerability of SAMITAL and the impact on patients reported outcomes. Conditions: Head-and-neck Squamous Cell Carcinoma, Oral Mucositis Intervention / Treatment: DRUG: SAMITAL®, DRUG: Placebo sachets Location: Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Histologically proven squamous cell carcinomas of the head-and-neck * Eligible primary tumor sites: oral cavity, oropharynx, larynx, hypopharynx * Stage III or IV disease without evidence of distant metastases * Patients candidate to definitive concurrent chemo-radiotherapy or induction chemotherapy followed by chemo-radiotherapy * Age >= 18 years * Karnofsky Performance Status >=70 * Life expectancy >=6 months * Able to swallow and retain oral medication * Good state of dentition * Patients must be available for treatment and follow-up * Confirmation of adequate contraception use by the patient and/or partner * Signed informed consent Exclusion Criteria: * Previous radiotherapy of the oral cavity, and/or oropharynx, larynx, hypopharynx * Serious co-morbidities: uncontrolled heart disease, heart failure within 6 months prior to study participation, history of serious neurological and/or psychiatric abnormalities. * Chronic administration of steroids or immunosuppressants * Pregnancy.

Study Objectives This clinical trial studies the use of gallium-68 (68Ga)-DOTA-Bombesin as the imaging agent for positron emission tomography (PET)/magnetic resonance imaging (MRI), collectively PET-MRI, in patients with prostate cancer. PET uses a radioactive substance called 68Ga-DOTA-Bombesin, which attaches to tumor cells with specific receptors on their surfaces. The PET scanner takes pictures that capture where the radioactive drug is "lighting up" and attaching to tumor cells, which may help doctors recognize differences between tumor and healthy prostate tissue. MRI uses radio waves and a magnet to make a picture of areas inside the body. Using 68Ga-DOTA-Bombesin in diagnostic procedures, such as PET/MRI, may allow doctors to identify smaller tumors than standard imaging. Conditions: Prostate Carcinoma Intervention / Treatment: DRUG: 68Ga-DOTA-Bombesin, PROCEDURE: Magnetic Resonance Imaging (MRI) scan, PROCEDURE: Positron Emission Tomography (PET) scan 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 * Provides written informed consent * Known diagnosis of prostate cancer * Patient has suspected recurrence based on biochemical data [prostate-specific antigen (PSA) > 2 ng/mL] * Able to remain still for duration of each imaging procedure (about one hour) EXCLUSION CRITERIA * Unable to provide informed consent * Inability to lie still for the entire imaging time * Inability to complete the needed investigational and standard-of-care imaging examinations due to other reasons (severe claustrophobia, radiation phobia, etc.) * Any additional medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study compliance * Metallic implants

Study Objectives The purpose of this study is to investigate the activity of MORAb-009 when added to a standard regimen of gemcitabine in patients with previously untreated unresectable stage 3 or 4 pancreatic cancer. Conditions: Pancreatic Cancer Intervention / Treatment: DRUG: MORAb-009, DRUG: Placebo, DRUG: Gemcitabine Location: Germany, Canada, Spain, United States, Belgium Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * Female or male subjects, >= 18 years of age, with cytologically or histologically confirmed diagnosis of pancreatic adenocarcinoma. * Must have measurable disease, as defined by RECIST or evaluable by clinical signs/symptoms (e.g. ascites, pleural effusion, or lesions of less than 2 cm) supported by biomarker, radiologic, or pathologic studies conducted within 4 weeks prior to study entry. * Must have unresectable disease and have received no prior chemotherapy or radiation therapy for their pancreatic cancer. * Karnofsky performance status of greater than or equal to 70 %. * Female subjects of childbearing potential and all male subjects must be surgically sterile or consent to use a medically acceptable method of contraception throughout the study period. * Other significant medical conditions must be well-controlled and stable in the opinion of the investigator for at least 30 days prior to Study Day 1. * Laboratory and clinical results within the 2 weeks prior to Study Day 1 as follows: Absolute neutrophil count (ANC) >= 1.5 x 109/L Platelet count >= 100 x 109/L Hemoglobin >= 9 g/dL Serum bilirubin <= 2.0 mg/dL Aspartate transaminase (AST)* <= 5 x upper limit of normal (ULN) Alanine transaminase (ALT)* <= 5 x ULN Alkaline phosphatase* <= 5 x ULN Serum creatinine <= 2.0 mg/dL Stenting to reduce liver functions to qualifying levels is permitted. * Subjects with liver function abnormalities greater than the ULN are eligible only if in the opinion of the investigator they are due to disease obstruction of the bile ducts or metastatic disease. * Must be willing and able to provide written informed consent. Exclusion Criteria: * Known central nervous system (CNS) tumor involvement. * Evidence of other active malignancy requiring treatment. * Clinically significant heart disease (e.g., congestive heart failure of New York Heart Association Class 3 or 4 angina not well controlled by medication, or myocardial infarction within 6 months). * Electrocardiogram (ECG) demonstrating clinically significant arrhythmias (Note: Subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia [SVT], are eligible). * Active serious systemic disease, including active bacterial or fungal infection. * Active viral hepatitis or symptomatic human immunodeficiency virus (HIV) infection. * Prior chemotherapy or radiation therapy for their pancreatic cancer. * Breast-feeding, pregnant, or likely to become pregnant during the study. * No other concurrent immunotherapy (e.g., immunosuppressants or chronic use of systemic corticosteroids with the exception that low-dose corticosteroids are allowed) * Known hypersensitivity to a monoclonal antibody or biologic therapy.

Study Objectives In this study, the investigators will use P-HDFL, a regimen with high tumor remission rate (\~ 60-70%) and with only modest treatment-associated toxicities, as induction chemotherapy for patients with non-resectable gastric cancer. For those patients who have achieved complete response (CR) or partial response (PR), DI will be used to "consolidate" the remission. For those patients who fail to achieve remission by P-HDFL, DI will be used as salvage chemotherapy. The efficacy and toxicities of DI in these two settings will be evaluated in this prospective study. Conditions: Gastric Cancer Intervention / Treatment: DRUG: Docetaxel-Irinotecan Location: Taiwan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed gastric adenocarcinoma * Measurable or evaluable disease * No previous C/T * Age 16 ~ 75 years * Karnofsky Performance Status of 60% * 4 weeks after R/T * Adjuvant C/T: the last dosing of C/T 6 months before enrollment * WBC >= 4,000, platelets >= 100K, Creatinine <= 1.5mg/dl and proteinuria <1+, normal serum bil, transaminase <= 3.5x ULN, TG > 70mg/dl Exclusion Criteria: * CNS metastasis * Patients receive concomitant anti-cancer C/T or R/T * Patients who are pregnant and with an expected life expectancy less than 3 months * Symptomatic heart disease, active infection, extensive liver disease, or liver cirrhosis

Study Objectives The French cooperative group GINECO proposes to implement an observational study to describe a real situation, in daily practice tolerance and methods of administration of bevacizumab (Avastin ®) Conditions: Epithelial Ovarian Cancer Intervention / Treatment: DRUG: Bevacizumab Location: France Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Patients aged 18 years and over, * Patients with an epithelial ovarian cancer, fallopian tube or peritoneal who will receive bevacizumab (Avastin ®) in first-line therapy * Patients should be informed of the study orally and should not have any objection their data to be processed. Exclusion Criteria: * Patient participation in a clinical trial * Patient non-affiliated to a social security scheme.

Study Objectives The purpose of this study is to assess efficacy and safety of belinostat in combination with carboplatin and paclitaxel in patients with previously untreated carcinoma of unknown primary. Conditions: Carcinoma of Unknown Primary Intervention / Treatment: DRUG: belinostat, carboplatin, paclitaxel, DRUG: carboplatin, paclitaxel Location: Denmark, United States, France, Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patients with CUP where the primary site had not been revealed by complete history, physical examination (including gynecological examination when appropriate), computed tomography (CT) scan of the chest, abdomen and pelvis, bilateral mammography (in women with adenocarcinoma or poorly differentiated carcinoma), routine laboratory studies (complete blood cell counts, electrolytes, urinalysis, liver and renal function tests), and directed work-up of any other symptomatic areas. * Light microscopic pathologic diagnosis of adenocarcinoma (including poorly differentiated), squamous cell carcinoma, or poorly differentiated carcinoma. Patients with poorly differentiated carcinoma must have immunohistochemical stains to confirm the diagnosis of carcinoma, and to rule out other tumor types. Note: patients with a light microscopic histology diagnosis of "poorly differentiated neoplasm, not otherwise classified" did not fulfill the criteria for inclusion, unless immunohistochemical staining confirmed the diagnosis of carcinoma. * Signed consent of an IRB ([Institutional Review Board])/IEC ([Independent ethics committee]) approved ICF ([Informed Consent Form]). * At least one measurable lesion according to RECIST ([response evaluation criteria in solid tumors ]) criteria. Note, target lesions could only be selected within previously irradiated areas if newly arising or clearly progressing after irradiation as proven by repeat scanning * Performance status Eastern Cooperative Oncology Group (ECOG) <= 2. * Age >= 18 years. * A negative serum or urine pregnancy test for women of childbearing potential. Postmenopausal women must have been amenorrheic for >= 12 months to be considered of non-childbearing potential. * Serum potassium within normal range. * Acceptable coagulation status: Prothrombin time/International normalized ratio PT/INR ([international normalized ratio]), and activated partial thromboplastin time (APTT) <= 1.5 × upper limit of normal (ULN) or in the therapeutic range if on anticoagulation therapy. * Acceptable liver, renal and bone marrow function including the following: 1. Bilirubin <= 1.5 times ULN (if liver metastases were present, then <= 3 × ULN was allowed). 2. Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), alanine amino transferase/serum glutamic pyruvic transaminase (ALT/SGPT), and alkaline phosphatase <= 3 times ULN (if liver metastases were present, then <= 5 × ULN was allowed). 3. An estimated creatinine clearance >= 45 mL/min using an appropriate formula (Appendix C, protocol version 1.0, Appendix 16.1.1), or measured ethylenediaminetetraacetic acid (EDTA) renal clearance >= 45 mL/min. 4. Absolute neutrophils count >= 1.5 × 109/L, platelets >= 100 × 109/L. 5. Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L (patients with chronic anemia due to underlying disease and its treatment could undergo blood transfusion prior to treatment in order to meet this criteria). Exclusion Criteria: * Patients with well recognized subsets of CUP site where treatments directed towards a defined tumor type, or surgery, alternatively radiotherapy, can be advised: * Women with adenocarcinoma involving only axillary lymph nodes. * Women with papillary serous carcinoma of the peritoneum. * Women with adenocarcinoma with positive staining for estrogen receptor (ER) or progesterone receptor. * Young men (< 45 years) with poorly differentiated carcinoma consistent with an extragonadal germ cell tumor (carcinoma involving mediastinum or retroperitoneum, or elevated levels of beta-human chorionic gonadotropin or alpha-fetoprotein). * Men with bone metastases and/or adenocarcinoma, and abnormally elevated PSA ([Prostate specific antigen]) in their plasma. * Patients with squamous cell carcinoma involving only cervical lymph nodes, or inguinal lymph nodes. * Patients with neuroendocrine carcinomas determined according to standard pathology diagnosis procedures, including stains. * Patients with potentially completely resectable metastatic disease, or disease which can be adequately treated with radiotherapy only. * Patients with brain or meningeal metastases. Note, patients with adequately treated brain metastases, e.g. surgically resected, or adequately controlled by radiotherapy, with no residual neurological symptoms due to metastases and no steroid treatment required, could be enrolled. If clinical suspicion, adequate investigations should be performed to rule out brain metastases or meningeal involvement. * Prior systemic anti-tumor therapy, including chemotherapy administered in association to radiotherapy for sensitization, for CUP. Note, prior radiotherapy or surgery was allowed provided treatment was completed at least 4 weeks before randomization. * Treatment with investigational agents, including non-anti-tumor agents, within the last 4 weeks before randomization. * Co-existing active severe infection or any co-existing medical condition assessed by the Investigator as likely to interfere with study procedures. * Significant cardiovascular disease (New York Heart Association Class III or IV cardiac disease), myocardial infarction within the past 6 months, unstable angina, unstable arrhythmia or a need for anti-arrhythmic therapy (use of medication to control heart rate in patients with atrial fibrillation was allowed, if on stable medication for at least the last month prior to randomization and the medication not listed as causing Torsade de Points (Section 13.2, Appendix B, protocol version 1.0, Appendix 16.1.1), or evidence of acute ischemia on ECG. * Marked baseline prolongation of QT/QTc ([corrected QT interval]) interval, i.e., demonstration of a QTc interval > 450 millisecond (ms); Long QT Syndrome; the required use of concomitant medication that may cause Torsade de Pointes (Section 13.2, Appendix B, protocol version 1.0, Appendix 16.1.1). * Altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures. * History of a previous malignancy within 5 years with the exception of non-metastatic non-melanoma skin cancer or cervical carcinoma in situ. Prior systemic therapy for other malignancy completed at least 5 years before randomization is allowed. Implemented with amendment 2 (study centers in France only): History of a previous malignancy, irrespective of time since diagnosis/treatment, with the exception of non metastatic non-melanoma skin cancer or cervical carcinoma in situ. * Known hypersensitivity to either platinum compounds or paclitaxel, or any components of the study medications, and inability for desensitization. * Known infection with HIV, or known active Hepatitis B or C infection. * Peripheral neuropathy >= Grade 2. * Pregnant or lactating females. * Women of childbearing age and potential who are not willing to use effective contraception during the study and until 30 days after last dose of study drug. Male patients or male patients who have female partners of childbearing age and potential who are not willing to use effective contraception during the study and until 30 days after last dose of study drug. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intra uterine devices, sexual abstinence or vasectomized partner. * Patients that are not affiliated with social security (study centers in France only). * Implemented with amendment 1 (study centers in Denmark only): Hearing impairment assessed by the Investigator as being of such a degree that treatment with carboplatin cannot be initiated. * Implemented with amendment 1 (study centers in Denmark only): Bleeding tumors.

Study Objectives The purpose of the study is to determine if pulse steroids are more efficacious and safer than the standard treatment with oral corticosteroids. Conditions: Hemangiomas Intervention / Treatment: DRUG: prednisolone, DRUG: methylprednisolone Location: Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * problematic facial hemangiomas (periorbital/facial hemangiomas with potential visual obstruction, large/dysfiguring hemangiomas) * 1-4 months of age * signed consent form Exclusion Criteria: * refusal to participate * age > 4 months * complicated nonvisible hemangiomas * congenital heart disease

Study Objectives The primary objective of this study is to assess the safety and feasibility of the following two regimens: Cohort A) phased regimen of pembrolizumab in which paclitaxel is followed by paclitaxel plus pembrolizumab and Cohort B) concurrent regimen of paclitaxel plus pembrolizumab. The primary safety objective is to evaluate the overall grade 3 or 4 treatment-related adverse event rate for each cohort and compare them to relevant historical controls. Conditions: Breast - Female, Male Breast Cancer Intervention / Treatment: DRUG: Pembrolizumab, DRUG: Paclitaxel Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria Subjects must meet all of the following criteria: * Histologically or cytological confirmed diagnosis of HER2-negative metastatic breast cancer or locally advanced disease not amenable to resection. * Available ER and PR status from tumor sample with either hormone receptor positive or negative tumor(s). * For subjects with hormone receptor-positive, HER2-negative metastatic breast cancer, they are eligible if they have already received or been intolerant to at least two lines of endocrine therapies (including the adjuvant and/or metastatic setting), or are appropriate candidates for chemotherapy (i.e. large burden of visceral disease). * Measurable disease by RECIST 1.1, or evaluable bone disease, i.e., bone lesions that are lytic or mixed (i.e. lytic + sclerotic) in the absence of measurable lesion. Refer to section 11 for the evaluation of measurable disease. * Male or female age >=18 years. * ECOG performance status 0, 1 or 2. * Must have normal organ and marrow function as defined below: * Hematologic - Absolute neutrophil count >=1,500/mcL - Platelets >=75,000/mcL - Hemoglobin >= 9 g/dL * Renal * Creatinine <= 1.5X ULN or * Measured or calculated creatinine clearance (CrCl) >= 30 mL/min for subject with creatinine levels > 1.5X ULN [CrCl should be calculated per institutional standard; GFR can also be used in place of creatinine or CrCl] * Hepatic * Total bilirubin <=1.5X ULN or for subjects with total bilirubin levels >1.5X ULN, direct bilirubin <=ULN * AST(SGOT)/ALT(SGPT) <=2.5X ULN * Coagulation * PT and PTT <= 1.5X ULN; subjects receiving anticoagulant therapy are eligible if PT or PTT is within therapeutic range of intended use of anticoagulants per investigator discretion. * INR <= 1.5; Patients receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation per investigator discretion. * Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to receiving C1D1. * Female subjects of childbearing potential must be willing to use an adequate method of birth control as outlined in Section 8.1.10, be surgically sterile, or abstain from heterosexual activity for the course of the study and 120 days after the last dose of study therapy. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. Male subjects of reproductive potential should agree to use an adequate method of contraception starting with the first dose of study therapy and 120 days after the last dose of study therapy. Abstinence is acceptable if this is the established and preferred contraception for the subject. * Has completed the screening requirement of a core or punch biopsy of a tumor lesion per Section 5 (bone tissue not acceptable). Biopsy of the breast tumor or other regional areas is acceptable (i.e. lymph nodes, skin lesions). * Subjects who are unable to meet the screening requirement of a tumor biopsy due to inaccessible tumor, subject safety concern, or bone-only disease may submit an archived tumor specimen from primary tumor or metastatic biopsy collected within 12 months from consent. * Subjects who decline tumor biopsy may submit archived tumor specimen as specified above (within 12 months from consent) only after Sponsor-Investigator approval. * Ability to understand and the willingness to sign the written informed consent document. Exclusion Criteria Subjects must not meet any of the following criteria: * Prior chemotherapy within 3 weeks, prior targeted small molecule therapy or radiation therapy within 2 weeks, or prior anti-cancer monoclonal antibody (mAb) for direct anti-neoplastic treatment within 4 weeks prior to Cycle 1 Day 1. * Not recovered (i.e., <= Grade 1) from adverse events due to agents previously administered. o Note: Subjects with <= Grade 2 neuropathy or alopecia of any grade are an exception and may qualify for the study. * More than three prior lines of chemotherapy for HER2-negative metastatic disease or for locally advanced disease that is not amenable to resection. o Note: Non-Chemotherapy regimens do not count as prior lines (ex: hormonals, biologics) * Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137) or has participated in Merck MK-3475 trial(s) and received MK-3475 as part of protocol therapy. * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Cycle 1 Day 1 * Has had major surgery within 3 weeks prior to Cycle 1 Day 1. * Has received any other investigational agents within 4 weeks of Cycle 1 Day 1 of study therapy. * Known active uncontrolled or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis as indicated by clinical symptoms, cerebral edema, and/or progressive growth. o Note: Subjects with treated CNS metastases are eligible if they are asymptomatic, have no requirement for steroids, no requirement for anticonvulsants, and stable CNS radiographic study showing no significant vasogenic edema >= 4 weeks since completion of radiation and >= 2 weeks since discontinuation of steroids. * History of known allergic reaction to paclitaxel * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might 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. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment. Pregnant women are excluded from this study because paclitaxel is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with paclitaxel, breastfeeding should be discontinued if the mother is treated with paclitaxel. These potential risks also apply to pembrolizumab being used in this study. * Has a known history of Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency disorder (AIDS). HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with paclitaxel and pembrolizumab. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. * Has known active infection with hepatitis B or hepatitis C. * Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). o Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Has a known additional malignancy that progressed or required active treatment within the last 5 years. o Note: Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer. * Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. * Has an active infection requiring systemic therapy. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Has received a live vaccine within 30 days of Cycle 1 Day 1 of study therapy. o 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.

Study Objectives Phase II trial to study the effectiveness of combining oblimersen with interferon alfa in treating patients who have metastatic renal cell (kidney) cancer. Interferon alfa may interfere with the growth of tumor cells. Oblimersen may increase the effectiveness of interferon alfa by making tumor cells more sensitive to the drug. Conditions: Recurrent Renal Cell Cancer, Stage IV Renal Cell Cancer Intervention / Treatment: BIOLOGICAL: recombinant interferon alfa, BIOLOGICAL: oblimersen sodium, OTHER: pharmacological study Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed, measurable metastatic renal cell cancer; if a nephrectomy was performed in the setting of metastatic disease, post-nephrectomy progression of metastases must be documented * Performance status 0-2 (SWOG), life expectancy > 3 months * Prior radiation must have been completed > 4 weeks before enrollment, with measurable disease outside of the radiation port * WBC > 3500/μl * Absolute neutrophil count > 1500/μl * Platelets > 100,000/μl * Transaminases < 2 x institutional upper limit of normal * Serum bilirubin < 1.5 x institutional upper limit of normal (if Gilbert's, up to 2 x upper limit) * Serum alkaline phosphatase < 2.5 x institutional upper limit of normal * Patients with hepatic metastases may have 50% higher levels of all the above-listed parameters * Serum creatinine < 1.5 x institutional upper limit of normal * Patients with active or recently-treated autoimmune disease are excluded, as are patients currently receiving or expected to require corticosteroid therapy * Prior malignancy is limited to adequately treated non-melanoma skin cancer, cervical carcinoma-in-situ, or any other malignancy for which the patient has been disease-free for at least 5 years * Because the effects of G3139 on the unborn fetus or newborn infant are unknown, pregnant or lactating women are excluded, and patients with reproductive potential must agree to use a medically-acceptable form of birth control * Patients must have fully recovered from the effects of any prior surgery or medical illness such as infection; those with psychosocial problems that might compromise safety or protocol compliance are excluded * Central venous access is required * Patients may have received up to two prior biological therapy regimens, excluding exposure to either of the therapy agents and patients may have had no more than one prior chemotherapy regimen; full recovery from all toxicities must have occurred; for high-dose IL-2, at least 8 weeks must have elapsed since prior treatment * Written, voluntary informed consent * Previous chemotherapy must have been completed at least 3 weeks before treatment under this protocol can be initiated * Patients with a history of brain metastases, or who are currently being treated, or have untreated brain metastases, are not eligible; Note: if patient received steroid therapy, at least three weeks must have elapsed prior to entry on this protocol * Patients must have normal baseline PT/PTT; Note: For those patients taking low dose coumadin (e.g., as prophylaxis for a venous access device) and INR of up to 1.5 is allowed

Study Objectives In patients with cancer induced bone pain, addition of Syndros will improve pain relief and decrease opioid requirement. Conditions: Bone Metastases, Breast Cancer, Pain Intervention / Treatment: DRUG: Syndros Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: EARLY_PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Be capable of understanding the investigational nature of the study and all pertinent aspects of the study * Be capable of signing and providing written consent in accordance with institutional and federal guidelines * Have metastatic breast cancer with bone metastases * Be willing and able to comply with scheduled visits, treatment plan, and follow up with research staff * Age >= 21 years * Must be on opioid therapy for bone pain for at least 4 weeks Exclusion Criteria: * Have a known sensitivity to dronabinol or alcohol * Have a history of hypersensitivity reaction to alcohol * Using medical marijuana currently * Using Syndros for nausea or appetite stimulant * Receiving or have received disulfiram- or metronidazole- containing products within past 14 days * Are currently pregnant or are of child-bearing age and refuse to use adequate contraception * Have a history of psychiatric illness * Have a history of seizure disorders

Study Objectives The aim of the study was to investigate the safety and efficacy of Toripalimab Combined With Double Platinum Based Chemotherapy for Potentially Resectable Non-driver Gene Mutation Non-small Cell Lung Cancer. Conditions: Advanced Non Small Cell Lung Cancer Intervention / Treatment: DRUG: Toripalimab combination with platinum-containing dual-drug chemotherapy Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Previously untreated, histologically confirmed potentially resectable stage IIIA or IIIB (AJCC staging eighth edition) NSCLC; potentially resectable refers to a discussion by the surgeon, including primary T3 or T4, mediastinum Lymph node metastasis (N2) is defined as: single-site or multi-station metastasis can be confirmed by imaging or pathology with a short diameter >= 2 cm, and it is expected that resection is difficult or pneumonectomy is required; * Before the enrollment, submit the PD-L1 immunohistochemistry section and the corresponding pathology report for biomarker evaluation (the tumor tissue sample must be fresh or archived samples obtained within 3 months before enrollment; Fresh tissue must be a needle biopsy, excision or incision biopsy specimen); Exclusion Criteria: Patients received Toripalimab before Patients with contraindication of chemotherapy Pregnant or breast feeding women