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Study Objectives This phase II trial studies how well sapanisertib works in treating patients with pancreatic neuroendocrine tumor that has spread to other places in the body (metastatic), does not respond to treatment (refractory), or cannot be surgically removed. Drugs such as sapanisertib may stop the growth or shrink tumor cells by blocking some of the enzymes needed for cell growth. Conditions: Pancreatic Neuroendocrine Tumor G1, Pancreatic Neuroendocrine Tumor G2, Refractory Pancreatic Neuroendocrine Carcinoma Intervention / Treatment: DRUG: Sapanisertib Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must have unresectable or metastatic, histologically confirmed low or intermediate grade (Klimstra Criteria) pancreatic neuroendocrine tumor (PNET) with radiological evidence of disease progression since last treatment * Refractory disease to treatment with an mTOR inhibitor * Patients with 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, are ineligible * Disease that is currently not amenable to surgery, radiation, or combined modality therapy with curative intent * Patients must not have poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma * Patients must have measurable disease * Documented radiological evidence for disease progression (measurable or nonmeasurable) =< 12 months prior to enrollment * NOTE: If patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation; at least one measurable lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) * Prior or concurrent therapy with somatostatin analogue (SSA) is permitted; a stable dose at least 2 months prior to study start and must continue on the stable dose while receiving study treatment; SSA is not considered as systemic treatment * Recovered from adverse events to grade 1 or less toxicity according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE 4.0) due to agents administered previously * NOTE: Chemotherapy-induced alopecia and grade 2 neuropathy are acceptable * Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * Patients must be able to swallow intact capsules * Leukocytes >= 3,000/mm^3 (within less than or equal to 14 days prior to registration) * Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (within less than or equal to 14 days prior to registration) * Hemoglobin >= 10 g/dL (within less than or equal to 14 days prior to registration) * Platelets >= 100 x 10^9/L (within less than or equal to 14 days prior to registration) * Total serum bilirubin =< institutional upper limit of normal (ULN) (within less than or equal to 14 days prior to registration) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (within less than or equal to 14 days prior to registration) * Serum creatinine =< 1.5 X institutional ULN and creatinine clearance >= 60 ml/min (within less than or equal to 14 days prior to registration) * NOTE: Creatinine clearance must be calculated using the Cockcroft-Gault equation * Glycosylated hemoglobin (HbA1c) < 7.0% (within less than or equal to 14 days prior to registration) * Fasting serum glucose =< 130 mg/dL (within less than or equal to 14 days prior to registration) * Fasting triglycerides =< 300 mg/dL (within less than or equal to 14 days prior to registration) * Diabetics are allowed if: * Fasting blood glucose (FBG) =< 130 mg/dL (mmol/L), OR * HbA1c =< 7% * Women must not be pregnant or breast-feeding due to potential harm to the fetus from MLN0128 (TAK-228); all females of childbearing potential must have a blood test or urine study within 7 days of registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) * Women of child-bearing potential and men must agree to practice 1 highly effective method of contraception and 1 additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through 90 days (for female patients) and 120 day (for male patients) after the last dose of study drug, or agree to completely abstain from heterosexual intercourse; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men must agree not to donate sperm during the course of this study or within 120 days after receiving their last dose of study drug * Patients who have a history of brain metastasis are eligible for the study provided that all the following criteria are met: * Brain metastases which have been treated * No evidence of disease progression for >= 3 months before the first dose of study drug * No hemorrhage after treatment * Off-treatment with dexamethasone for 4 weeks before administration of the first dose of TAK-228 * No ongoing requirement for dexamethasone or anti-epileptic drugs * Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care Exclusion Criteria: * Patient is INELIGIBLE if patient discontinued prior mTOR inhibitor due to toxicity * Patients must NOT have radiotherapy, or major surgery or active drug therapy for pNET (SSA permitted) within 4 weeks prior to study treatment start * Patient must NOT have had previous treatment with any PI3K or AKT inhibitor * NO hepatic artery embolization or cryoablation/radiofrequency ablation of hepatic metastasis within 2 months of study treatment start * Patients must NOT have previous or concurrent malignancy within 2 years; exceptions are made for patients who meet any of the following conditions: * Adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer OR * Adequately treated stage I or II cancer currently in complete remission, or any other cancer that has been in complete remission for at least 2 years * No more than 3 prior systemic treatment regimens for advanced PNET * Patients with a history of the following within =< 6 months of study entry are NOT eligible: * Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures * Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures * Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia) * New York Heart Association (NYHA) class III or IV heart failure * Pulmonary embolism * Patients with known significant active cardiovascular or pulmonary disease at the time of study entry are INELIGIBLE including: * Uncontrolled hypertension (i.e., systolic blood pressure >180 mm Hg, diastolic blood pressure > 95 mm Hg); use of anti-hypertensive agents to control hypertension before cycle1 day 1 is allowed * Pulmonary hypertension * Uncontrolled asthma or oxygen (O2) saturation < 90% by arterial blood gas analysis or pulse oximetry on room air * QT syndrome, or torsades de pointes * Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement * Medically significant (symptomatic) bradycardia * History of arrhythmia requiring an implantable cardiac defibrillator * Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long * Patients with known manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of MLN0128 (TAK-228) are INELIGIBLE * Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are INELGIBLE because of the potential for pharmacokinetic interactions with MLN0128 (TAK-228) * NO treatment with strong inhibitors and/or inducers of cytochrome P450 (CYP) 3A4, or CYP2C19 within 1 week preceding the first dose of study drug * NO patients receiving systemic corticosteroids (either intravenous [IV] or oral steroids, excluding inhalers or low-dose hormone replacement therapy) within 1 week before administration of the first dose of study drug * Patients CANNOT have daily or chronic use of a proton pump inhibitor (PPI) and/or having taken a PPI within 7 days before receiving the first dose of study drug

Study Objectives To determine how long Gemcitabine and Bevacizumab will stop the cancer from growing in patients with advanced breast cancer. Conditions: Metastatic Breast Cancer, Locally Advanced Breast Cancer Intervention / Treatment: DRUG: Gemcitabine, 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: * Must be female and greater than or equal to 18 yrs of age * Participants must have confirmed cancer with measurable or evaluable, locally recurrent or metastatic disease. * Participants must have received a taxane as neo-adjuvant and/or adjuvant therapy * Participants may have received prior hormone therapy for locally recurrent or metastatic disease Exclusion Criteria: * Participants with breast cancer overexpressing Human Epidermal growth factor Receptor 2 (HER2) gene amplification * Prior chemotherapy or targeted therapy for metastatic breast cancer * Prior treatment with gemcitabine, trastuzumab, lapatinib or bevacizumab in any setting * History of, or active brain mets * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to treatment, or anticipation of need for major surgical procedure during course of study * Prior history of high blood pressure crisis * Have a serious, nonhealing wound, ulcer, or bone fracture

Study Objectives The purpose of this study is to test the safety of the investigational drug, selinexor (KPT-330), in combination with carboplatin and paclitaxel chemotherapy, where paclitaxel will be given at two different dosing schedules and selinexor will be given at two different dosing schedules. Carboplatin and paclitaxel chemotherapy is a commonly used therapy for the treatment of advanced or recurrent ovarian, fallopian tube, primary peritoneal, or endometrial cancer. The investigators want to find out what effects, good and/or bad, selinexor has on the patient and the cancer. Conditions: Ovarian Cancer, Endometrial Cancer Intervention / Treatment: DRUG: Paclitaxel, DRUG: Carboplatin, DRUG: Selinexor 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 must have MSKCC pathologically confirmed diagnosis of one of the following tumor types: Ovarian, fallopian tube or primary peritoneal cancer, Ovarian carcinosarcoma, Endometrial cancer, Endometrial carcinosarcoma * All patients with ovarian, fallopian tube or primary peritoneal cancer and ovarian carcinosarcoma must have recurrent disease, and only one prior line of chemotherapy that must have been platinum-based chemotherapy for the management of primary disease. This initial platinum-based treatment may have included intraperitoneal therapy, consolidation/maintenance and/or biologic/targeted agents (e.g., bevacizumab, PARP inhibitor) as part of first-line treatment. * Patients with endometrial cancer or endometrial carcinosarcoma may either be chemotherapy naive OR have had one prior line of chemotherapy that must have been a platinum-based chemotherapy regimen in the adjuvant or advanced/recurrent setting. The initial platinum-based treatment may have included consolidation/maintenance and/or biologic/targeted agents as part of first-line treatment. Patients entering the trial chemotherapy naive MUST have Stage IVB or recurrent disease AND have disease that is not amenable to curative intent. * Patients must have measurable disease (RECIST 1.1). Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be greater than or equal to 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or greater than or equal to 20 mm when measured by chest x-ray. Lymph nodes must be greater than or equal to 15 mm in short axis when measured by CT or MRI. * Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy. * Be at least 18 years of age. * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. * Have adequate bone marrow, renal, hepatic and neurologic functions as defined by the following: Bone marrow function: * Absolute neutrophil count (ANC) >= 1.5 x 109/L * Platelets >= 100 x 109/L * Hemoglobin >= 9 g/dL Renal function: * Creatinine <= 1.5 x ULN OR creatinine clearance >= 30 mL/min (Cockcroft-Gault calculation) Hepatic function: * Bilirubin <= 1.5 x ULN * AST and ALT <= 3 x ULN (less than or equal to 5 x upper limit of normal for patients with liver involvement of their cancer) (ULN = institutional/laboratory upper limit of normal; LLN = institutional/laboratory lower limit of normal) * Neurologic function: Neuropathy (sensory and motor) less than or equal to Grade 1. * Patients must have recovered from effects of recent surgery, radiotherapy, chemotherapy or biologic/targeted therapy to baseline or CTCAE less than or equal to Grade 1 (excluding alopecia or other non-clinically significant AE's). * Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to study treatment initiation. * Any other prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted therapy and immunologic therapy, must be discontinued at least 3 weeks prior to study treatment initiation. * Any investigation agents must be discontinued at least 30 days prior to study treatment initiation. * Any prior radiation therapy must be discontinued at least 4 weeks prior to study treatment initiation. * At least 4 weeks must have lapsed since major surgery (e.g., laparotomy, laparoscopy, thoracotomy, video assisted thoracoscopy) prior to study treatment initiation. * Patients must be willing and able to swallow oral tablets. * Patients must have signed an approved informed consent and authorization permitting the release of personal health information. * Patients of childbearing potential must have a negative pregnancy test prior to the study entry and be practicing an effective form of contraception. Sexually active subjects must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 4 months after the last dose of study drug, even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug. Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects. Exclusion Criteria: * Patients who are pregnant or nursing. * Patient who have had previous treatment with selinexor. * Patients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures which are not controlled, any brain metastases and/or epidural disease, or history of cerebrovascular accident (CVA, stroke) within six months prior to the first date of study treatment. * Patients requiring drainage gastrostomy (e.g., drainage PEG tube) and/or parenteral hydration and/or nutrition. * Patients with clinically significant cardiovascular disease. This includes: * Uncontrolled hypertension, defined as systolic greater than or equal to 160 mm Hg or diastolic greater than or equal to 100mm Hg despite antihypertensive medications. * Myocardial infarction or unstable angina within 6 months prior to the first date of study treatment. * New York Heart Association (NYHA) Class II or greater congestive heart failure. * History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or serious cardiac arrhythmia requiring medication. This does not include asymptomatic atrial fibrillation with controlled ventricular rate. * Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms. Note: if initial QTcF is found to be >500 ms, two additional ECG's separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is less than or equal to 500 ms, the subject meets eligibility in this regard. * Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, or put the study outcomes at undue risk * Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to the first date of study treatment. * Patients with macular degeneration, uncontrolled glaucoma, or markedly decreased visual acuity

Study Objectives This is a prospective, single-arm, monocentric translational study designed to evaluate possible biomarkers of resistance to the first line of therapy with pazopanib in patients with metastatic renal cell carcinoma (mRCC) who have not received systemic therapy in both the adjuvant and metastatic phases. Conditions: Metastatic Renal Cell Carcinoma Intervention / Treatment: DRUG: Pazopanib Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Signed Informed Consent Form * Unresectable advanced or metastatic renal cell carcinoma (RCC) with component of clear cell histology and/or component of sarcomatoid histology that has not been previously treated with any systemic agent, including treatment in the adjuvant setting * Availability of a representative formalin-fixed paraffin-embedded fractional Fokker-Planck equation (FFPE) tumor specimen collected within 24 months of starting first-line pazopanib that enables the definitive diagnosis of renal cell carcinoma (RCC) (the archival specimen must contain adequate viable tumor tissue to enable candidate biomarkers status; the specimen may consist of a tissue block or at least 15 unstained serial sections; for core needle biopsy specimens at least two cores should be available for evaluation) * Measurable disease as defined by RECIST v1.1 * Age >=18 years Hematology Absolute neutrophil count (ANC)>=1.5 X 109/L Hemoglobin >=9 g/dL (5.6 mmol/L) Platelets >=100 X 109/L Prothrombin time (PT) or international normalized ratio (INR)b <=1.5 X upper limit of normal (ULN) Activated partial thromboplastin time (aPTT) <=1.5 X upper limit of normal (ULN) Hepatic Total bilirubin <=1.5 X upper limit of normal (ULN) Alanine amino transferase (ALT) and Aspartate aminotransferase (AST)c 2.5 X upper limit of normal (ULN) Patients with documented liver metastases <5 X upper limit of normal (ULN) Renal Serum creatinine 1.5 mg/dL (133 µmol/L) Or, if >1.5 mg/dL: Calculated creatinine clearance (ClCR) (reference appropriate appendix) >=30 mL/min to >= 50 mL/min Urine Protein to Creatinine Ratio (UPC; appropriate appendix)<1 Or, 24-hour urine protein <1g * Eastern Cooperative Oncology Group (ECOG) performance Status 0-1 Exclusion Criteria: * Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: active peptic ulcer disease, known intraluminal metastatic lesion/s with risk of bleeding, inflammatory bowel disease (e.g. ulcerative colitis, Chrohn's disease), or other gastrointestinal conditions with increased risk of perforation, history of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment. * History of any one or more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) - Poorly controlled hypertension [defined as systolic blood pressure (SBP) of >=140 millimetre (s) of mercury (mmHg) or diastolic blood pressure (DBP) of >= 90 millimetre (s) of mercury (mmHg)]. Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Following antihypertensive medication initiation or adjustment, blood pressure (BP) must be re-assessed three times at approximately 2-minute intervals. At least 24 hours must have elapsed between anti-hypertensive medication initiation or adjustment and BP measurement. These three values should be averaged to obtain the mean diastolic blood pressure and the mean systolic blood pressure. The mean SBP / DBP ratio must be <140/90 millimetre (s) of mercury (mmHg) (OR 150/90 millimetre (s) of mercury (mm Hg), if this criterion is approved by Safety Review Team) in order for a subject to be eligible for the study * History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible * Major surgery or trauma within 28 days prior to first dose of pazopanib and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery). * Evidence of active bleeding or bleeding diathesis. * Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage Note: Lesions infiltrating major pulmonary vessels (contiguous tumour and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating (abutting) the vessels is acceptable (CT with contrast is strongly recommended to evaluate such lesions). * Large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed. * Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed. * Recent hemoptysis (½ teaspoon of red blood within 8 weeks before first dose of study drug). * Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures. * Treatment with any of the following anti-cancer therapies: * chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of Pazopanib

Study Objectives This research study is studying a targeted therapy as a possible treatment for relapsed or refractory Waldenstrom's Macroglobulinemia (WM). This study is using the study intervention ABT-199. Conditions: Waldenstrom Macroglobulinemia Intervention / Treatment: DRUG: ABT199 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: * Clinicopathological diagnosis of Waldenstrom's Macroglobulinemia and meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenstrom's macroglobulinemia (Owen 2003; Kyle 2003). * Measurable disease, defined as presence of serum immunoglobulin M (IgM) with a minimum IgM level of > 2 times the upper limit of normal of each institution is required. * Have received at least one prior therapy for WM. * Age >= 18 years. * ECOG performance status <2 (see Appendix A). * Participants must have normal organ and marrow function (growth factors cannot be given prophylactically to establish eligibility) as defined below: * Absolute neutrophil count > 1,000/mm3 * Platelets > 50,000/mm3 * Hemoglobin > 8 g/dL * Total bilirubin <= 1.5 mg/dL or < 2 mg/dL if attributable to hepatic infiltration by neoplastic disease * AST (SGOT) and ALT (SGPT) < 2.5X the institutional upper limit of normal * Creatinine clearance >=50 ml/min * Not on any active therapy for other malignancies with the exception of topical therapies for basal cell or squamous cell cancers of the skin. * Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or have or will have complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) while participating in the study; and 2) for at least 28 days after discontinuation from the study. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. FCBP must be referred to a qualified provider of contraceptive methods if needed. * Able to adhere to the study visit schedule and other protocol requirements. * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * Any serious medical condition, laboratory abnormality, uncontrolled intercurrent illness, or psychiatric illness/social condition that would prevent the participant from signing the informed consent form. * Concurrent use of any other anti-cancer agents or treatments or any other study agents. * Prior exposure to ABT-199 or BCL2 inhibitors. * Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, ECG finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the patient, including symptomatic hyperviscosity; alter the absorption, distribution, metabolism or excretion of ABT-199; or impair the assessment of study results. * Grade > 2 toxicity (other than alopecia) continuing from prior anti-cancer therapy. * Known CNS lymphoma. * Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening. * New York Heart Association classification III or IV heart failure. * Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. * Known history of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and/or Hepatitis C Virus (HCV) infection. * Lactating or pregnant women. * Inability to swallow tablets. * History of non-compliance to medical regimens. * Unwilling or unable to comply with the protocol.

Study Objectives The primary purpose of this study is to determine the highest dose of ON 01910.Na that can be safely given as an intravenous infusion over 24 hours once a week in a 3-week cycle to patients with advanced solid tumors. Conditions: Solid Tumors, Advanced Cancer, Cancer, Neoplasms Intervention / Treatment: DRUG: rigosertib sodium 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: * Must have histologically confirmed solid tumor (leukemias and lymphomas excluded) malignancy that is incurable and for which standard (FDA approved or established standard clinical practice), curative, or palliative measures do not exist or are no longer effective. * Patients with disease amenable to sequential biopsies will be requested to undergo two tumor biopsies and two normal skin biopsies, but patients may decline and still be eligible for enrollment during this escalation stage. * At least 3 weeks since the last dose of other potentially myelosuppressive treatment (at least 6 weeks since last dose of nitrosoureas or mitomycin C) and recovery from manifestations of reversible drug toxicity (alopecia, stable residual neuropathy, and residual hand and foot syndrome are excluded). Patients with prior doxorubicin chemotherapy must have total cumulative dose of no more than 450 mg/m2. * Patients with prior radiotherapy are eligible provided a minimum of 4 weeks have passed and the maximal area of hematopoietic active bone marrow treated was less than 25%. * ECOG performance status <=2. * Patients must have nearly normal organ and marrow function as defined below: * Hgb > 9 gm/dl (must not require transfusional support but erythropoietin therapy is permitted) * WBC > 4,000 per microliter * Absolute neutrophil count > 1,500 per microliter * Platelets >= 100,000 per microliter * Total bilirubin within 1.5 times institutional upper normal limit * AST(SGOT)/ALT(SGPT) <= 2.5 x institutional upper normal limit. (If liver function abnormalities are due to metastatic disease, patients are eligible provided the transaminases are < 5 times institutional upper normal limit. Patients with primary liver disease with these parameters will be ineligible.) * Serum creatinine within normal institutional limits or estimated creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. * Women of child-bearing potential and men must agree to use adequate contraception prior to study entry. * Ability to understand and the willingness to sign a written informed consent document. * All ethnic groups are eligible for this trial. Inclusion Criteria - Dose Confirmation Phase Same inclusion criteria as in the Dose Escalation phase described above, except Patients must have an ECOG performance of 0 or 1. Exclusion Criteria: * Recent major surgery (within the past 14 days), chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) or radiotherapy within 4 weeks prior to entering the study, or those who have not recovered from adverse events (except alopecia, stable residual neuropathy, and residual hand and foot syndrome) due to previously administered agents. * Patients may not be on any other investigational agents or concurrent chemotherapy, radiotherapy, hormonal treatments, bone marrow transplantation, or immunotherapy. Patients who have previously had a Bone Marrow Transplant are excluded from this study. * Known brain metastases, except brain metastases that have been previously removed or irradiated and currently have no clinical impact. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to ON 01910.Na. * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, bleeding, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant and nursing women are excluded. * HIV-positive patients receiving combination anti-retroviral therapy are excluded. * Ascites requiring active medical management including paracentesis, peripheral bilateral edema, hyponatremia (serum sodium value less than 134 Meq/L).

Study Objectives Trial objectives: To decide whether the addition of nelfinavir to the approved antimyeloma therapy with bortezomib and dexamethasone has sufficient activity in proteasome inhibitor-resistant myeloma patients to merit further clinical investigation in a prospective controlled trial. Additional research questions: To collect myeloma cell samples from proteasome inhibitor-resistant myeloma patients for the assessment of the biology of proteasome inhibitor resistance and the identification of predictive markers for response to nelfinavir-based antimyeloma therapy. Conditions: Myeloma Intervention / Treatment: DRUG: Nelfinavir, DRUG: bortezomib, DRUG: Dexamethasone Location: Switzerland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patient must give written informed consent prior to any protocol-specific procedure. * Patient was diagnosed with multiple myeloma based on standard IMWG criteria, and has received at least one previous line of chemotherapy. * Patient has been exposed to or is intolerant to at least one IMID (thalidomide, lenalidomide, pomalidomide). * A therapy with bortezomib in the approved dose and schedule, based on Swissmedic approval (treatment of patients with relapsed/refractory multiple myeloma who have received at least one prior line of therapy), is indicated and intended. * Patient is refractory to his/her most recent proteasome inhibitor-containing regimen, based on divers criteria. * WHO performance status <= 3. * Age >= 18 years. * Adequate hematological values: platelets >= 50 x 109/L, hemoglobin >= 80 g/L (both may be achieved by transfusion). * Adequate hepatic function: bilirubin <= 1.5 x ULN (for patients with suspected hemolysis: direct bilirubin <= 1.5 x ULN), ALT <= 3 x ULN (<= 5 x ULN if liver infiltration by myeloma suspected, based on imaging results). * Calculated creatinine clearance >= 15 mL/min, according to the formula of Cockcroft-Gault, see Appendix 1). * Women are not breastfeeding. Women with child-bearing potential are using effective contraception (see 9.8), are not pregnant and agree not to become pregnant during participation in the trial and during the 12 months thereafter. A negative pregnancy test before inclusion (within 7 days) into the trial is required for all women with child-bearing potential. Men agree not to father a child during participation in the trial and during 12 months thereafter. * Completed baseline QoL questionnaire. Exclusion Criteria: * Evidence of ongoing uncontrolled systemic infections. * History of chronic active HCV or HBV. * Evidence of myeloma within the CNS. * Psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, filling out quality of life (QoL) forms, or interfering with compliance for oral drug intake. * Exposure to another experimental drug within 3 weeks prior to trial entry. * Any serious underlying medical condition (at the judgment of the investigator) which may impair the ability of the patient to participate in the trial, in particular any uncontrolled clinically significant active disease (e.g. active autoimmune disease, uncontrolled diabetes, uncontrolled cardiac disease). * Non-hematologic active malignancy within the past 5 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas. * Concomitant use of other anti-cancer medication or radiotherapy except for local pain control. The use of bisphosphonates is allowed. * Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to enrollment. * Known hypersensitivity to bortezomib or nelfinavir or hypersensitivity to components of these drugs. * Any psychological, familial, sociological or geographical condition likely hampering compliance with the trial protocol and follow-up. * Patient who takes the following drugs during the trial therapy, which cannot be replaced or paused.

Study Objectives This study is designed to assess the safety and efficacy of a combination of ipilimumab and fotemustine in Patients with Unresectable Locally Advanced or Metastatic Malignant Melanoma. Conditions: Metastatic Malignant Melanoma Intervention / Treatment: DRUG: Ipilimumab and Fotemustine Location: Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologic diagnosis of malignant melanoma * Stage III (unresectable) or Stage IV melanoma * Maximum 1 line of chemotherapy for advanced disease allowed * No prior chemotherapy within 4 weeks from treatment start (6 weeks in case of nitrosourea) * No previous systemic corticosteroid therapy within 10 days * Prior adjuvant treatment with IFN or other immunotherapy allowed * Asymptomatic brain metastases allowed * Measurable disease * Prior treatment of brain metastases. In case stereotactic radiotherapy (or surgery) was not applicable, whole brain radiotherapy should have been performed * Life expectancy >= 16 weeks * ECOG performance status of 0 or 1 * Normal laboratory tests were required * Negative screening tests for HIV, Hepatitis B, and Hepatitis C. * Men and women, of and over 18 years old. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study in such a manner that the risk of pregnancy is minimized. Exclusion Criteria: * Any malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix; * Primary ocular or mucosal melanoma. Medical History and Concurrent Diseases * Symptomatic brain metastases requiring immediate local intervention (radiotherapy (RT) and/or surgery) * Autoimmune disease * Any underlying medical condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea. Prohibited Treatments and/or Therapies * Concomitant therapy with any anti-cancer agent * Immunosuppressive agents * Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month prior to or after any dose of study drug); surgery or radiotherapy ; other investigational anti-cancer therapies; or chronic use of systemic corticosteroids ; * Previous treatment with other investigational products, including cancer immunotherapy, within 30 days; * Previous enrollment in another clinical trial or prior treatment with a CD137 agonist or anti-CTLA-4 and/or fotemustine. Sex and Reproductive Status * WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the study; * Women who are pregnant or breastfeeding; * Women with a positive pregnancy test on enrollment or prior to investigational product administration; * Sexually active fertile men not using effective birth control if their partners are WOCBP. Other Exclusion Criteria * Prisoners or subjects who are involuntarily incarcerated; * Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.

Study Objectives To estimate the time to progression of cancer in patients with previously untreated mesothelioma receiving cisplatin, pemetrexed and bevacizumab Conditions: Mesothelioma Intervention / Treatment: DRUG: bevacizumab, DRUG: cisplatin, DRUG: pemetrexed 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 *2.1 Patients must have histologically proven malignant mesothelioma (epithelial, sarcomatoid, or mixed subtype) not amenable to curative surgery or radiotherapy. Eligible sites of origin include the pleura, peritoneum, and tunica vaginalis. *2.2 Patient's disease must not be amenable to curative treatment with surgery. Evidence of gross unresectability will include but not be limited to direct extension into the chest wall, mediastinal or hilar lymphadenopathy, pulmonary or cardiac function that is inadequate to tolerate resection, and sarcomatoid or mixed histology. *2.3 Patients must be > 18 years old 5.2.4 Patients must have measurable disease. Adequate organ function and functional status Exclusion Criteria: a. General Medical Concerns 5.3.1 Patients must not be pregnant or breast feeding. 5.3.2 No "currently active" second malignancy other than non-melanoma skin cancer. Patients are not considered to have a "currently active" second malignancy if they have completed therapy and have a less than 30% risk of relapse. *3.3 No uncontrolled intercurrent illness including but not limited to: active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric/social situations that would limit compliance with study requirements. *3.4 No HIV positive patients receiving combination anti-retroviral therapy because of possible pharmacokinetic interactions with study medications. *3.5 History of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab or other agents used in the study. *3.6 Inability to interrupt aspirin or other non-steroidal medication for a 5 day period. c. Bevacizumab-Specific Concerns Subjects meeting any of the following criteria are ineligible for study entry: *3.7 Patients with brain metastases are excluded 5.3.8 History of myocardial infarction or CVA (stroke) within 6 months of study entry. *3.9 Evidence of bleeding diathesis or coagulopathy. Patients on therapeutic doses of coumadin are eligible as long as the INR is maintained in the range of 2-3 and there is no evidence of active bleeding. *3.10 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 5.3.11 Urine protein:creatinine ratio less than 1.0 at screening 5.3.12 Serious, non-healing wound, ulcer, or bone fracture

Study Objectives The purpose of this study is to collect beginning information on whether intravenous (IV) administration of KRN5500 is safe and effective for treatment of neuropathic pain in patients with cancer. Conditions: Neuropathic Pain Intervention / Treatment: DRUG: KRN5500, DRUG: Placebo Location: United States, Puerto Rico Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * >= 18 years * Diagnosis of advanced or recurrent cancer * No options for curative chemotherapy, but palliative chemotherapy allowed under certain conditions * Refractory neuropathic pain rated 4 or greater on 0-10 scale and failure to respond to 2 commonly used treatments * If taking opioids for pain, stable regimen over past week before enrolling * Karnofsky performance status of 40 or more * Females must be sterile or post-menopausal Exclusion Criteria: * Radiation to site of neuropathic pain for past 4 weeks * Major surgery within past 2 weeks * Liver function and other key labs outside normal parameters * ECG showing significant abnormality * Myocardial Infarction (heart attack) within past 6 months * History of interstitial lung disease * History of severe allergic reaction to drugs containing polysorbate 80 * Other investigational drug within 2 weeks or 5 half-lives (whichever is longer

Study Objectives The purpose of this study is to determine whether erlotinib plus pemetrexed, cisplatin are effective and safe in treating lung adenocarcinoma with brain metastases. Conditions: Lung Adenocarcinoma, Brain Metastases Intervention / Treatment: DRUG: erlotinib, DRUG: pemetrexed, DRUG: cisplatin, DRUG: erlotinib Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histological or cytological diagnosis of lung adenocarcinoma histology with brain metastases * >= 18 years * Eastern Cooperative Oncology Group (ECOG) Performance Status no more than 3 (poor PS caused by neurological symptom) * Appraisable intracranial disease, the presence of at least one lesion, and the longest diameter > 5 mm by brain MRI * Haemoglobin 10.0 g/dl, Absolute neutrophil count (ANC) 1.5^9/L, platelets 100 x 10^9/L * Total bilirubin 1.5 x upper limit of normal (ULN) * alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN in the absence of liver metastases, or < 5 x ULN in case of liver metastases * Creatinine clearance 60ml/min (calculated according to Cockcroft-gault formula) * If received brain radiotherapy, patients included at least 8 weeks after the end of radiotherapy. Exclusion Criteria: * Mixed non-adenocarcinoma cell lung cancer histology * Previous treatment with pemetrexed or tarceva * Be allergic to pemetrexed or tarceva

Study Objectives The purpose of this study is to determine the Maximum Tolerated Dose (MTD) of 4SC-201 (Resminostat) in combination with FOLFIRI and whether 4SC-201 (Resminostat) is effective and safe in combination FOLFIRI versus FOLFIRI alone in the treatment of advanced colorectal carcinoma. Conditions: Advanced Colorectal Carcinoma Intervention / Treatment: DRUG: 4SC-201(Resminostat), DRUG: FOLFIRI Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria Phase I: * Histologically or cytologically confirmed advanced stage colorectal carcinoma * Documented progression after precedent treatment according to RECIST criteria * ECOG performance status 0 - 2 * Live expectancy of 12 weeks or more * Patients must have previously received treatment with 5-FU alone or in combination with other anti-tumor medications * Patients foreseen for chemotherapy with FOLFIRI in second or further line treatment Exclusion Criteria Phase I: * Patients who have received previous treatment with an HDAC inhibitor * Anticipation of need for a major surgical procedure or radiation therapy (RT) during the study * Therapy with agents known to prolong the QT interval, such as certain antibiotics (e.g. erythromycin, clarithromycin), antidepressants (e.g. doxepin, amitryptiline) or neuroleptics (e.g. haloperidol, clozapine) * Patients who are homozygous for the UGT1A1 and characterized by the presence of an additional TA repeat in the TATA sequence of the UGT1A1 promoter ((TA)7TAA)). For patients having shown good tolerability of irinotecan in a precedent treatment line according to the investigator's judgement, availability of UGT1A1 result is not mandatory for study inclusion * Therapy with strong CYP3A4 inhibitors (e.g. ketoconazole) or inductors (e.g. carbamazepine, phenytoin, St. John's Wort) * Severe internal disease: insufficiently treated or uncontrolled arterial hypertension, hemoptoe, New York Heart Association (NYHA) grade II or greater congestive heart failure, symptomatic coronary heart disease, myocardial infarction (<= 12 months prior to inclusion), serious cardiac arrhythmia requiring medication, peripheral arterial occlusive disease stage II or greater, uncontrolled severe disease * Patients with a confirmed QTcF > 480 ms, or a history of additional risk factors for Torsades de Pointes * Major surgery within the last 4 weeks Inclusion Criteria Phase II : * Histologically or cytologically confirmed advanced stage colorectal carcinoma * Documented progression after precedent treatment according to RECIST criteria * K-ras mutation (which contraindicates EGFR inhibitor therapy, results from local pathology will be accepted for inclusion * ECOG performance status 0 - 2 * Live expectancy of 12 weeks or more * Patients must have previously received treatment with 5-FU alone or in combination with other anti-tumor medications * Patients foreseen for chemotherapy with FOLFIRI in second line treatment Exclusion Criteria Phase II arm: * Patients who have received previous treatment with an HDAC inhibitor * Anticipation of need for a major surgical procedure or radiation therapy (RT) during the study * Therapy with agents known to prolong the QT interval, such as certain antibiotics (e.g. erythromycin, clarithromycin), antidepressants (e.g. doxepin, amitryptiline) or neuroleptics (e.g. haloperidol, clozapine) * Patients who are homozygous for the UGT1A1 and characterized by the presence of an additional TA repeat in the TATA sequence of the UGT1A1 promoter ((TA)7TAA)). * Therapy with strong CYP3A4 inhibitors (e.g. ketoconazole) or inductors (e.g. carbamazepine, phenytoin, St. John's Wort) * Severe internal disease: insufficiently treated or uncontrolled arterial hypertension, hemoptoe, New York Heart Association (NYHA) grade II or greater congestive heart failure, symptomatic coronary heart disease, myocardial infarction (<= 12 months prior to inclusion), serious cardiac arrhythmia requiring medication, peripheral arterial occlusive disease stage II or greater, uncontrolled severe disease * Patients with a confirmed QTcF > 480 ms, or a history of additional risk factors for Torsades de Pointes * Major surgery within the last 4 weeks

Study Objectives The purpose of this study is to evaluate the efficacy and safety of PEG-rhG-CSF in patients with breast cancer receiving chemotherapy Conditions: Breast Cancer Intervention / Treatment: DRUG: PEG-rhG-CSF, DRUG: rhG-CSF Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patients with age between 18 and 70 years * diagnosis of breast cancer patients * chemotherapy naive * Karnofsky Performance Status >= 70 * Written informed consent are acquired Exclusion Criteria: * uncontrolled infection * Have accepted radiotherapy within 4 weeks before anticipated the study * pregnancy * Other situations that investigators consider as contra-indication for this study

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

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

Study Objectives This is a phase II, single arm, open-label, multicenter study to evaluate the efficacy and safety of Surufatinib single agent or Surufatinib combined with Toripalimab in patients with advanced solid tumors. Conditions: Advanced Solid Tumors Intervention / Treatment: DRUG: Surufatinib, DRUG: Toripalimab Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Adequately understand the study and voluntarily sign the Informed Consent Form; * 18-75 years old; * Histologically or cytologically confirmed advanced solid tumors (focusing on neuroendocrine neoplasmas (NENs), biliary tract cancer, gastric cancer, thyroid cancer, small cell lung cancer, non-small cell lung cancer, soft tissue sarcoma, endometrial cancer and esophageal squamous cell carcinoma, etc); * Fail or cannot tolerate the standard therapies, or for whom no effective standard therapy is available, or refuse standard therapy; * NSCLC cohort: no prior chemotherapy or any other systemic therapy for stage IV NSCLC with positove PD-L1 expression; * Have a performance status (PS) of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale; * Have measurable lesions (according to RECIST 1.1); * Agree to provide histology samples; * Lab tests within 7 days before first dose: 1. Absolute neutrophil count (ANC) >=1.5×10^9/L, platelet count >=100×10^9/L, and hemoglobin >=9 g/dL; 2. Serum total bilirubin <1.5 times the upper limit of normal (ULN); 3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels <= 1.5 times the ULN without liver metastases; and ALT and AST <= 3 times ULN with liver metastases; 4. Serum creatinine <1.5 times ULN and creatinine clearance >=50 mL/min; 5. Urine protein < 2+; if >=2+, 24-hour urine protein <1 g; 6. International Normalized Ratio (INR) <=1.5 ULN and activated partial thromboplastin time (APTT) <=1.5 ULN; * Have expected survival of more than 12 weeks; * Male or females patients with reproductive potential must agree to use an effective contraceptive method, for example, double-barrier device, condom, oral or injected birth control medication or intrauterine device, during the study and within 90 days after study treatment discontinuation. All female patients are considered to be fertile, unless the patient had natural menopause or artificial menopause or sterilization (such as hysterectomy, bilateral oophorectomy or ovarian irradiation). Exclusion Criteria: * Toxicity from a previous anti-tumor treatment that does not return to Grade 0 or 1 (except for hair loss or Grade <= 2 peripheral neurotoxicity caused by oxaliplatin); * Other malignancies diagnosed within the previous 5 years, except skin basal cell carcinoma or skin squamous cell carcinoma or cervical carcinoma in situ; * Symptomatic central nervous system (CNS) metastasis or cancerous meningitis (meningeal metastasis) during the screening period; * Systematic anti-tumor therapy received within 4 weeks prior to first dose, including chemotherapy, biotherapy, targeted therapy, hormonotherapy, and anti-tumor Chinese medicine treatment; * Radical radiotherapy within 4 weeks prior to first dose, radioactive seed implantation within 60 days prior to first dose, or Palliative radiotherapy for a bone metastasis lesion within 1 week prior to first dose; * Functional NENs which need to be treated with long acting Somatostatin analogues (SSAs) to control disease related syndromes, such as insulinoma, gastrinoma, glucagonoma, somatostatinoma, ACTHoma, VIPoma, accompanied by carcinoid syndrome, Zollinger-Ellison syndrome or other active symptoms; * Previously treated with anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody, anti-CTLA-4 antibody, any other antibody acting on the T cell stimulation or checkpoint pathway or Surufatinib; * Previously received anti-VEGF/VEGFR targeted drugs and progressed during the treatment or within 4 months after these drugs; * Thyroid dysfunction with symptoms or require treatment when screening except hypothyroidism controlled only by thyroid hormone replacement therapy, the level of TSH in patients with iodine refractory differentiated thyroid cancer is more than 0.1 mU/L (or other corresponding unit level) before the beginning of the study treatment; * Previously received immunosuppressive drugs except locally or temporarily used glucocorticoids; * Autoimmune disease with systematic treatment or autoimmune disease history within 2 years; * Previously received systematic immunologic stimulants within 4 weeks prior to the first dose; * Inoculated with any live vaccine or attenuated live vaccine within 4 weeks or planed to inoculate during the study; * Major surgery within 4 weeks or unhealed wound/fracture; * Uncontrolled malignant hydrothorax, ascites, or pericardial effusion; * Under anti-hypertension treatment, still uncontrolled hypertension, defined as: systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg; * Disease or situation that affects drug absorption, or unable to take drugs orally; * Previously received CYP3A4 strong inducers or strong inhibitors within 1 week or 5 half-life periods; * Active gastric and duodenal ulcers, ulcerative colitis and other digestive disease, gastrointestinal tumor with active bleeding, or other gastrointestinal conditions that may cause bleeding or perforation by investigator's discretion; * History or presence of a serious hemorrhage (>30 ml within 2 months), hemoptysis (>5 ml blood within 4 weeks) within 2 months; * History or presence of an artery thrombosis or deep venous thrombosis within 6 months, or a thromboembolic event (including transient ischemic attack) within 12 months; * Clinically significant cardiovascular disease, including but not limited to, acute myocardial infarction within 6 months prior to first dose, severe/unstable angina pectoris or coronary artery bypass grafting, congestive heart failure according to the New York Heart Association (NYHA) classification >= 2; ventricular arrhythmias which needs drug treatment; left ventricular ejection fraction (LVEF) <50%; * Severe electrolyte abnormalities with clinical significance by investigator's discretion; * Any clinically significant active infection, or unknown reason fever prior to first dose (temperature > 38.5℃); * Active tuberculosis, on treatment or previously received antituberculosis therapy within 1 year; * History or presence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia or severely injured lung function except radiation pneumonia in the radiotherapy area; * A positive immunodeficiency virus (HIV) test; * History of clinically significant hepatic disease, including, but not limited to, known hepatitis B virus (HBV) infection with HBV DNA positive (copies >=1×10^3/ml or > 200 IU/ml); known Hepatitis C virus (HCV) infection with HCV RNA positive (copies >=1×10^3/ml); or liver cirrhosis, etc.; * Previously received investigational treatments unlisted in China within 4 weeks prior to first dose; * Women who are pregnant or lactating; * Previously allergic to any of the JS001 or Surufatinib ingredients, or monoclonal antibody; * Any other conditions are inappropriate for the use of the investigational products by investigator's discretion.

Study Objectives The primary objectives of this study are: 1. To explore the antitumor activity of MEDI-522 in combination with docetaxel, prednisone, and zoledronic acid in patients with metastatic Androgen-Independent Prostate Cancer (AIPC); and 2. To summarize the safety of MEDI-522 in combination with docetaxel, prednisone, and zoledronic acid in this patient population. Conditions: Prostate Cancer Intervention / Treatment: BIOLOGICAL: MEDI-522, BIOLOGICAL: Docetaxel + Prednisone* + Zoledronic Acid Location: Hungary, Israel, Canada, United States, Belgium, Russian Federation, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Adult men at least 18 years of age at the time of randomization. * Metastatic, histologically or cytologically confirmed adenocarcinoma of the prostate that has progressed after start of androgen deprivation therapy, which includes prior orchiectomy or medical castration using leuteinizing hormone-releasing hormone (LHRH) antagonists such as leuprolide or goserelin (patients must remain on LHRH analogue therapy for the duration of the study if not surgically castrated). Progressive disease should be documented by: a. PSA progression (defined as two consecutive increases in PSA over a previous reference value, with the first increase in PSA occurring at a minimum of 1 week after the reference value [obtained within 2 months prior to study randomization] and confirmed by a subsequent increase in PSA whose value must be ³ 5 ng/mL prior to study randomization);41 and one of the following: i. Bone metastases (defined as ³3 foci on bone scan and confirmed radiologically within 1 month prior to study randomization); or ii. Measurable non-bony metastatic disease (documented by radiographic studies performed within 1 month prior to study randomization). * Serum testosterone levels <50 ng/dL documented in non-surgically castrated patients within 21 days prior to randomization. * Prior treatment with nonsteroidal antiandrogens (e.g., flutamide or bicalutamide) is allowed provided: * There is evidence of disease progression (defined in Inclusion Criteria #2) following withdrawal of antiandrogens; and b. At least 4 weeks for flutamide or 6 weeks for bicalutamide have passed since last treatment. * Prior treatment with ketoconazole and/or steroids is allowed provided at least 4 weeks have passed since last treatment. There are no restrictions for use of prednisone (5 mg twice daily) or another functionally equivalent oral corticosteroid for treatment of pain. * In the rare instance a patient is potent, he must agree to practice an effective method of contraception including condom or abstinence, unless his sexual partner is sterile, from the time of first administration of MEDI-522 or docetaxel through 30 days after the last dose of either docetaxel or MEDI-522, whichever is the last drug discontinued. * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 documented within 21 days prior to randomization. * Life expectancy, in the opinion of the investigator, of at least 6 months. * White blood cell (WBC) count >= 3,000/mm3; absolute neutrophil count (ANC) >= 1,500/mm3; platelet count >= 100,000/mm3; and hemoglobin ³ 9 g/dL documented within 21 days prior to randomization. * Bilirubin <= ULN; aspartate transaminase (AST)/alanine transaminase (ALT) £1.5 times ULN or if AST/ALT is >1.5 times ULN, then alkaline phosphatase must be £2.5 times ULN; serum creatinine <= 1.5 mg/dL; INR within normal range, unless a patient is receiving anticoagulation therapy; and corrected serum calcium between 8.0-11.5 mg/dL documented within 21 days prior to randomization. * Patients who had prior major surgery are eligible if at least 4 weeks have passed since their surgery and all surgical wounds have healed prior to study randomization. * Prior radiotherapy including therapeutic isotopes is allowed provided measurable or evaluable disease that is clearly progressing is present and all acute radiation-related toxicities have resolved prior to study randomization. * Prior treatment with unconventional therapy for malignancy (e.g., vitamins, St. John's Wort, PC-SPES, saw palmetto, or other herbal remedies) is allowed provided at least 4 weeks have passed since last treatment prior to randomization. * Written informed consent and HIPAA authorization (USA sites only) obtained from the patient prior to receipt of any study medication or beginning study procedures. Exclusion Criteria: * Prior chemotherapy for metastatic prostate cancer (prior adjuvant chemotherapy is allowed provided it is non-taxane based and at least 6 months have passed since last treatment). * Prior treatment with other investigational agents within 4 weeks prior to randomization. * Planned concurrent treatment with unconventional therapy for malignancy (e.g., vitamins, St. John's Wort, PC-SPES, saw palmetto, or other herbal other herbal remedies) based on medical history. Currently requiring anticoagulation (excluding use of heparin flush solutions for maintenance of catheter lines) for any thromboembolic disease based on medical history and physical examination. * Current or planned participation (from the time of randomization through 30 days after the last dose of either docetaxel or MEDI-522, whichever is the last drug discontinued) in a research protocol in which an investigational agent or therapy may be administered. * Any evidence of or history elicited by the investigator of prior treatment with MEDI-522 or MEDI-523. * Prior treatment with calcitonin, mithramycin, or gallium nitrate within 2 weeks prior to randomization. * Clinically evident central nervous system (CNS) metastasis. * History of prior malignancies within the past 5 years other than adequately treated basal cell or squamous cell skin cancer or Stage I or II cancer currently in complete remission; * Any evidence of or history elicited by the investigator of symptomatic cerebrovascular events (i.e., stroke or transient ischemic attack) within 6 months prior to randomization; or any history or evidence of pulmonary embolism or thrombophlebitis (including deep vein thrombosis) requiring anticoagulant therapy (e.g., warfarin or heparin). * Any evidence of or history elicited by the investigator of myocardial infarction or angina within 6 months prior to randomization. * Any evidence of or history elicited by the investigator of hematemesis, melena, hematochezia, or uncontrolled gross hematuria within 4 weeks prior to randomization. * Any evidence of or history elicited by the investigator of bleeding diatheses. * Major elective surgery planned from the time of randomization through 30 days after the last dose of either docetaxel or MEDI-522, whichever is the last drug discontinued. * Any evidence of or history elicited by the investigator of hypersensitivity to a previously administered monoclonal antibody. * Any evidence of or history elicited by the investigator of hypersensitivity to drugs formulated with polysorbate 80, prednisone (or other functionally equivalent oral corticosteroid), or zoledronic acid. * Known human immunodeficiency virus (HIV) or known active viral hepatic infections based on medical history and physical examination. * Any evidence of or history elicited by the investigator of uncontrolled or refractory hypertension or uncontrolled diabetes despite medication within 6 months prior to randomization. * Any evidence of or history elicited by the investigator of an active infection requiring parenteral anti-infective therapy. * A general medical or psychological condition or behavior, including substance dependence or abuse that, in the opinion of the investigator, might not permit the patient to complete the study or sign the informed consent.

Study Objectives The purpose of this study is to assess the safety and tolerability of the multiple receptor tyrosine kinase (RTK) inhibitor (including EGFR, VEGFR2, ErbB2, and EphB4) XL647 when given orally daily to adults with advanced solid tumors. Conditions: Cancer Intervention / Treatment: DRUG: XL647 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: * Subject has histologically confirmed malignancy that is metastatic or unresectable * Subject has disease that is assessable by tumor marker, physical, or radiologic means * Subject is at least 18 years old * Subject has an ECOG performance status <= 2 (Karnofsky >= 60%) * Subject has a life expectancy >= 3 months * Subject has normal organ and marrow function * Subject gives written informed consent * Subject must use an accepted method of contraception during the study * Female subjects of childbearing potential must have a negative pregnancy test Exclusion Criteria: * Subject has received anticancer treatment within 30 days of first dose of XL647 * Subject has received another investigational agent within 30 days of first dose of XL647 * Subject has known brain metastases * Subject has corrected QT interval (QTc) of > 0.45 seconds * Subject is currently receiving anticoagulation therapy with warfarin * Subject has uncontrolled intercurrent illness * Subject is pregnant or breastfeeding * Subject has known HIV

Study Objectives Estimation of the Maximum tolerated dose (MTD) and/or Recommended dose (RD) of LDK378 as a single agent when administered orally to Japanese patients with tumors characterized by genetic alterations in anaplastic lymphoma kinase (ALK) Conditions: Tumors Characterized by Genetic Alterations in Anaplastic Lymphoma Kinase (ALK) Intervention / Treatment: DRUG: LDK378 Location: Japan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: BASIC_SCIENCE Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with a locally advanced or metastatic malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists * Only patients with tumors characterized by genetic alterations in ALK. For non-small cell lung cancer (NSCLC), an ALK translocation must be detected by Fluorescent in situ hybridization (FISH) in >=15% of tumor cells. Local site documented results on ALK alteration are acceptable for enrollment of the patients. Central confirmation of local results is not required. --Eastern Cooperative Oncology Group (ECOG) performance status grade <= 2 * Adequate organ function * Dose-expansion part: Patients must have NSCLC that has progressed since prior therapy with alectinib. Alectinib must have been the only prior ALK inhibitor received by the patient prior to trial entry. Exclusion Criteria: * Patients with symptomatic Central Nerve System (CNS) metastases who are neurologically unstable or require increasing doses of steroids to control their CNS disease * Patients with unresolved nausea, vomiting or diarrhea > Common Terminology Criteria for Adverse Events (CTCAE) grade 1 * Other concurrent severe and/or uncontrolled medical conditions * Patients who have been treated with chemotherapy or biologic therapy or other investigational agent < 2 weeks prior to starting the daily dosing of the study drug for compounds with a half-life <= 3 days, and < 4 weeks prior to starting the daily dosing of the study drug for compounds with a prolonged half-life (< 6 weeks for patients that received nitrosoureas or mitomycin-C) * Unresolved toxicity greater than CTCAE grade 1 or unstable toxicity from previous anti-cancer therapy or radiotherapy (excluding neurotoxicity, alopecia, ototoxicity, lymphopenia), or incomplete recovery from previous surgery, unless agreed by Novartis and the Principal Investigator and documented * Patients who have received radiotherapy to lung within 4 weeks prior to starting the daily dosing of the study drug or patients who have not recovered from radiotherapy-related toxicities. For all other anatomic sites radiotherapy to a large volume (including whole brain radiotherapy) < 2 weeks prior to starting the daily dosing of the study drug, and patients who have received radiotherapy to a small volume (including stereotactic radiotherapy to the CNS) < 3 days prior to starting the study drug. Other protocol-defined inclusion/exclusion criteria may apply.

Study Objectives This is a Phase II, single-arm study of ofatumumab investigating the safety of an accelerated infusion schedule of ofatumumab in patients who have received at least one prior therapy for CLL. The primary endpoint is to evaluate the number of subjects able to complete infusion number 3 (2000 mg) within 15 minutes of the planned time. Conditions: Chronic Lymphocytic Leukemia Intervention / Treatment: DRUG: Ofatumumab 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: * CD20+ B-cell chronic lymphocytic leukemia (B-CLL) according to International Workshop on CLL Working Group (IWCLL WG) Diagnostic Criteria. * Have received at least one prior therapy for CLL. *If previously treated with ofatumumab must have achieved at least a partial response (PR) and maintained PR for >= 6 months. * Requires treatment according to IWCLL-Working Group guidelines. * Eastern Cooperative Oncology Group Performance Status (ECOG PS) <=1. * Laboratory parameters <=7 days prior to treatment initiation: 1. Creatinine <= 1.5 mg/dL upper limit normal (ULN) 2. Aspartate amino transferase (AST) or alanine amino transferase (ALT) <= 3.0 x ULN 3. Alkaline phosphatase (ALP) <= 3.0 x ULN 4. Total Bilirubin level of < 1.5 mg/dL x the institutional ULN unless secondary to Gilbert's disease (or pattern consistent with Gilbert's) * Hepatitis B sAg negative and HepB cAb negative. Note: Patients who are HepB sAg negative but are HepB cAb positive (regardless of HepB sAb status) will NOT be allowed. * Women of childbearing potential must have a negative serum pregnancy test performed <=72 hours prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately. * Accessible for treatment and follow-up. * Able to understand the nature of this study, give written informed consent prior to study entry, and comply with study requirements. * No prior antibody therapy for CLL within the previous 3 months. Exclusion Criteria: * Previous treatment with ofatumumab that resulted in a Grade 3 or 4 infusion reaction. * Treatment for CLL within last 4 weeks. (Patients who have received steroids or IVIG for autoimmune complications of CLL are eligible). * Current active hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease, per assessment by the treating physician). * Active bacterial or viral infection or infection requiring intravenous antibiotic treatment at the time of accrual. * Central nervous system lymphoma/CLL. * Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (i.e., Richter's transformation). * History of other malignancy <= 2 years of study entry which could affect compliance with the protocol or interpretation of results. History of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix, low grade, early-stage, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ (DCIS) of the breast treated with curative intent, are generally eligible. * Active hepatitis B or C or known HIV positive. * Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to visit 1, whichever is longer. * History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae. * Clinically significant cardiac disease including unstable angina, acute myocardial infarction (within 6 months of enrollment), congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities. * Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient.

Study Objectives This is an open-label, Phase 1, dose-escalation study to determine the recommended doses of STA-9090 (ganetespib) and docetaxel for the treatment of subjects with solid tumor malignancies. The safety and tolerability of the treatment will also be evaluated. Conditions: Solid Tumor Malignancies Intervention / Treatment: DRUG: STA-9090 (ganetespib) with Docetaxel 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: * Must have histologically confirmed metastatic or unresectable malignancy with evidence of progression * If subject has been treated with docetaxel, must have evidence of persistent or progressive disease * Measurable disease per RECIST * CNS metastases are permitted if treated and radiographically and clinically stable for 4 weeks prior to first dose * ECOG status less than or equal to 2 * Life expectancy greater than 3 months * Adequate hematological, hepatic and renal function as defined by protocol * Willingness and ability to comply with study requirements * Female subjects of childbearing age must have a negative pregnancy test at study entry * Female subjects of child bearing age and males must agree to use adequate contraception as defined in the protocol Exclusion Criteria: * Prior chemotherapy or investigational agents within 3 weeks or 5 times the agent's half life, whichever is shorter prior to first dose * Radiotherapy within 2 weeks of first dose * Surgery, radiotherapy or ablative procedure to the only area of measurable disease * Major surgery within 4 weeks of first dose * Poor venous access that would require an indwelling catheter for study drug administration * History of severe allergic or hypersensitivity reactions to STA-9090 or docetaxel or their diluents or excipients * Baseline QTc >470 msec or previous history of QT prolongation while taking other medications * Peripheral neuropathy > Grade 1 * Ventricular ejection fraction less than or equal to 55% at baseline * Treatment with chronic immunosuppressants. However subjects may receive steroids for stable CNS metastases * Women who are pregnant or lactating * Uncontrolled intercurrent illness

Study Objectives To assess the safety of copanlisib. Conditions: Lymphoma, Non-Hodgkin Intervention / Treatment: DRUG: Copanlisib (BAY 80-6946) Location: Bulgaria, Korea, Republic of, Turkey, Italy, Brazil, Greece, Taiwan, South Africa, Russian Federation, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed diagnosis of indolent B-cell NHL, with histological subtype limited to the following: * Follicular lymphoma (FL) grade 1-2-3a. * Small lymphocytic lymphoma (SLL) with absolute lymphocyte count < 5 x 10*9/L at the time of diagnosis and at study entry. * Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM). * Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal). * Patients must have received two or more prior lines of treatment. A previous regimen is defined as one of the following: at least two months of single-agent therapy, at least two consecutive cycles of polychemotherapy, autologous transplant, radioimmunotherapy. * Prior therapy must include rituximab and alkylating agents.Prior exposure to idelalisib or other PI3K inhibitors is acceptable (except to copanlisib) provided that there is no resistance. * Patients must be refractory to the last rituximab-based treatment, defined as no response or response lasting < 6 months after completion of treatment. Time interval to assess refractoriness will be calculated between the end date (last day) of the last rituximab-containing regimen and the day of diagnosis confirmation of the subsequent relapse. * Patients must have at least one bi-dimensionally measurable lesion (which has not been previously irradiated) according to the Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification. * Patients affected by WM, who do not have at least one bi-dimensionally measurable lesion in the baseline radiologic assessment, must have measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level >= 2 x upper limit of normal (ULN)and positive immunofixation test. * ECOG performance status <= 1 * Adequate bone marrow, liver and renal function Exclusion Criteria: * Histologically confirmed diagnosis of FL grade 3b. * Chronic lymphocytic leukemia (CLL). * Transformed disease (assessed by investigator): * histological confirmation of transformation, or * clinical and laboratory signs: rapid disease progression, high standardized uptake value (SUV) (> 12) by positron emission tomography (PET) at baseline if PET scans are performed (optional). * Bulky disease - Lymph nodes or tumor mass (except spleen) >= 7cm LD (longest diameter) * Known lymphomatous involvement of the central nervous system. * Uncontrolled arterial hypertension despite optimal medical management (per investigator's assessment). * Type I or II diabetes mellitus with HbA1c > 8.5% at Screening. * Known history of human immunodeficiency virus (HIV) infection. * Active clinically serious infections > CTCAE Grade 2 * Active Hepatitis B or hepatitis C * History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator) * History of having received an allogeneic bone marrow or organ transplant * Positive cytomegalovirus (CMV) PCR test at baseline * Pregnant or breast-feeding patients

Study Objectives The purpose of this study is to establish the Maximum Tolerated Dose (MTD) of OXi4503 given by weekly infusions to patients with advanced solid tumors. Conditions: Solid Tumors Intervention / Treatment: DRUG: OXi4503 Location: United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically proven cancer. * Written informed consent. * Age >= 18 years. * Life expectancy of at least 12 weeks. * World Health Organization (WHO) performance status of 0 or 1. * Adequate Hematological and biochemical indices to support investigational therapy. * All women of childbearing potential (WOCBP) must have a negative serum pregnancy test. * WOCBP and fertile men and their partners must agree to use an effective form of contraception during the study and for 90 days after the last dose of study medication. * Measurable and evaluable disease. * All toxic manifestations of previous treatment must have resolved. * Able to undergo MRI scanning. Exclusion Criteria: * Radiotherapy, endocrine therapy, immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosureas and Mitomycin-C) prior to treatment. * Pregnant and lactating women. * Major thoracic and/or abdominal surgery in the preceding four weeks from which the patient has not yet recovered. * Patients which have active uncontrolled infections. * Patients with any other condition that in the Investigator's opinion would not make the patient a good candidate for the clinical trial. * Patients known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV). * Previous or ongoing cardiac conditions. * Uncontrolled hypertension. * Patients taking any drug known to prolong the QTc interval. * Patients who have had any ischaemic or vascular damage from previous radiotherapy. * Patients taking warfarin or heparin. * Patients taking naproxen. * Patients taking supplements or multivitamins containing vitamin C. * Patients should not be taking any other investigational drug for the duration of the study. * Patients with brain metastases or neurological tissue involvement of the spinal column.

Study Objectives The purpose of this research study is to measure adherence to the study drug (Carac) for the treatment of actinic keratoses. Conditions: Actinic Keratosis Intervention / Treatment: DRUG: Fluorouracil 0.5% Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Any male or female 50 years of age or older with moderate to severe actinic keratoses of the face and anterior scalp diagnosed by a dermatologist will be eligible for participation. Exclusion Criteria: * Age less than 50. * Known allergy or sensitivity to topical Carac® in the subject. * Inability to complete all study-related visits. * Introduction of any other prescription medication, topical or systemic, for actinic keratosis while participating in the study. * Subjects should not receive surgical or cryotherapy while participating in the study. * Pregnant women, women who are breast feeding, or women of child bearing potential who are not practicing two acceptable methods of birth control

Study Objectives This research study is studying the changes in primary and metastatic brain tumor inflammation using positron emission tomography (PET) imaging using a radioactive substance called \[11C\] PBR28a, which is also known as peripheral benzodiazepine receptors (PBR), or PBR-PET. Conditions: Intracranial Tumors, Glioblastoma, Melanoma Intervention / Treatment: OTHER: PBR PET, BIOLOGICAL: Cancer Immunotherapy, RADIATION: Radiation and chemotherapy Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: DIAGNOSTIC Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Participants must have evidence of metastatic melanoma to the brain for Cohort A or histologically confirmed GBM for Cohorts Band C. * Those with newly diagnosed GBM but suspected to have pseudoprogression after completion of chemoradiation can enroll in Cohort C. * Participants must have measurable brain disease, defined as at least one lesion that is 10 mm in diameter. * Age > 18 years. * ECOG performance status <=2 (Karnofsky >=60%, see Appendix A) * Life expectancy of greater than 3 months. * Participants must have normal organ and marrow function as defined below: * leukocytes >=3,000/mcL * absolute neutrophil count >=1,500/mcL * platelets >=100,000/mcL * total bilirubin within normal institutional limits * AST(SGOT)/ALT(SGPT) <=2.5 × institutional upper limit of normal * creatinine within normal institutional limits --- OR * creatinine clearance >=60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal. * For Cohort A, only patients with metastatic melanoma to the brain for whom their treating physician has planned to give immunotherapy as monotherapy are eligible for this study. This can be in the setting of a clinical trial or not. * For Cohort B, only patients with GBM for whom their treating physician has planned to give immunotherapy are eligible for this study. This can be in the setting of a clinical trial or not. * For Cohort C, patients with newly diagnosed GBM who have completed standard temozolomide + radiation and have suspected pseudoprogression within the first 3 months of completing chemoradiation can enroll. * Patient must be able to undergo MRI and PET scans. * Patient must be maintained on a stable corticosteroid regimen for 5 days prior each MR-PET scan. * High or mixed affinity binders (Ala/Ala or Ala/Thr) based on genotyping result from PBR affinity test. This blood test will be performed as part of the screening process after consent has been obtained. * The effects of PBR on the developing human fetus are unknown. For this reason and because radiopharmaceuticals agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Radiopharmaceutical agents are known to be teratogenic. * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * History of allergic reactions attributed to compounds of similar chemical or biologic composition to PBR. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant women are excluded from this study because PBR is a radiopharmaceutical 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 exposure of the mother to PBR, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study. * HIV-positive participants are excluded because their immune system is compromised and may affect the interpretation of the imaging data. * Patients who are not suitable to undergo MRI or PET or use gadolinium contrast due to: * Claustrophobia * Presence of metallic objects or implanted medical devices in body (i.e. cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants) The craniotomy patients will all have titanium but this is MRI compatible * Sickle cell disease * Renal failure * Reduced renal function, as determined by creatinine clearance < 30 mL/min based on a serum creatinine level obtained within 28 days prior to registration

Study Objectives To evaluate the safety and effectiveness of Stealth liposomal doxorubicin hydrochloride (DOX-SL) in the long-term treatment of AIDS-related Kaposi's sarcoma (KS) in patients who previously had good responses to DOX-SL in controlled studies of limited duration, or those with KS who discontinued treatment with another Kaposi's sarcoma therapy because of inadequate efficacy or unacceptable toxicity. To provide a defined protocol for Kaposi's sarcoma patients for whom DOX-SL therapy is indicated. Conditions: Sarcoma, Kaposi, HIV Infections Intervention / Treatment: DRUG: Doxorubicin hydrochloride (liposomal) Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Masking: NONE

Inclusion Criteria Concurrent Medication: Allowed: * Prophylaxis for PCP, cryptococcal, and herpes infections, and antiretroviral therapy provided these doses have been stable for at least 1 month. * Maintenance therapy for tuberculosis, fungal, and herpes infections. * Therapy for new episodes of tuberculosis, fungal, and herpes infections except with potentially myelotoxic chemotherapy. * Foscarnet or ganciclovir for CMV infection. * Colony stimulating factors and erythropoietin. Patients must have: * Moderate to severe AIDS-related Kaposi's sarcoma. * Documented anti-HIV antibody. * No active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, Pneumocystis carinii, or other microorganisms (if under treatment with myelotoxic drugs). NOTE: * Eligible KS patients include those who have discontinued therapy in the control arm of a DOX-SL KS study because of side effects or inadequate efficacy OR other KS patients for whom DOX-SL is believed to be indicated. Patients must not be eligible for other Liposome Technology protocols comparing DOX-SL with established therapies. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: * Clinically significant cardiac disease. * Confusion or disorientation. Concurrent Medication: Excluded: * Other cytotoxic cancer chemotherapy. Patients with the following prior conditions are excluded: * Prior neoplasms treated with extensive chemotherapy that, in the investigator's opinion, has led to an irreversibly compromised marrow function. * History of idiosyncratic or allergic reaction to anthracyclines. * History of major psychiatric illness. Prior Medication: Excluded within the past 4 weeks: * Cytotoxic chemotherapy (other than in a qualifying Liposome Technology protocol). * Interferon treatment. Prior Treatment: Excluded within the past 3 weeks: * Radiation or electron beam therapy.

Study Objectives The purpose of this research study is to determine the safety of the combination of the two drugs cediranib and temsirolimus and the highest doses of these two drugs that can be given in combination to people safely. Cediranib is a drug that may stop blood supply to the tumor and therefore help keep cancer cells from growing. Temsirolimus is a drug that may stop cancer cells from growing. These drugs have been used in other research studies in ovarian and kidney cancer and these studies suggest that these drugs may help to keep cancer from growing in this research study. Conditions: Endometrial Cancer, Ovarian Cancer, Cervical Cancer, Fallopian Tube Cancer, Peritoneal Cancer Intervention / Treatment: DRUG: temsirolimus, DRUG: cediranib 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 with metastatic endometrial cancer * Patients with recurrent ovarian, fallopian and peritoneal cancer * Patients with recurrent cervical cancer * Patients may have either measurable or non-measurable disease * Up to one prior line of chemotherapy in the recurrent setting is allowed. Biologic therapies will be considered as a prior line but hormonal therapies do not count. * No prior VEGF inhibitor therapy allowed. * Toxic side effects related to prior chemotherapy or hormonal therapy must have resolved to less than or equal to grade 1 or to baseline (excluding alopecia), or for peripheral neuropathy to less than or equal to grade 2. * Subjects may begin AZD2171 and temsirolimus at least 3 weeks after their last dose of chemotherapy or hormonal therapy, assuming they are otherwise eligible. * 18 years of age or older * At present, the potential of AZD2171 for clinically significant drug interactions involving the CYP isozymes is unknown. Eligibility of patients receiving any medication or substances known to affect or with teh potential to affect the activity or PK of AZD2171 will be determined following review of their case by the principal investigator. * Subjects with treated limited stage basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the breast or cervix are eligible if they otherwise meet eligibility. Subjects with stage I or II cancer treated with curative intent are also eligible with no evidence of recurrent disease. * No evidence of preexisting uncontrolled hypertension. If patient has hypertension, it must be medically controlled prior to starting AZD2171. * Women of child-bearing potential must have a negative pregnancy test prior to study entry. Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation. * No therapeutic anticoagulation. The use of low dose warfarin, intermittent doses of TPA, or heparin flushes to prophylaxis against central venous catheter-associated clots is permitted. * ECOG Performance status 0-2 * Patients must have normal organ and marrow function as defined in the protocol Exclusion Criteria: * Patients who have had chemotherapy, radiotherapy, or major surgery within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier. * Patients may not be receiving any other investigational agents nor have participated in an investigational trial within the past 4 weeks. Prior bevacizumab is allowed. * Patients may not be receiving any medication that may markedly affect renal function. NSAIDs should be avoided if possible. * Patients with known brain metastases should be excluded from this clinical trial. A CT of the head is required prior to entry into the study. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD2171. * Mean QTc of 470msec or greater in screening electrocardiogram or history of familial long QT syndrome. * Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart * Uncontrolled intercurrent illness including, but not limited to hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Inability to take and absorb orally administered medication. * Pregnant women. Breastfeeding should be discontinued. * Major surgical procedure or medical interference with peritoneum or pleura within 4 weeks of baseline CA-125 assessments. This excludes the need for a paracentesis. * Subjects with a history of an active malignancy during the last 3 years except non-melanomatous skin cancer, in situ breast or cervical cancer or stage I or II cancer treated with a curative intent and no active cancer recurrence. * HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD2171. * New York Heart Association classification of III or IV * Conditions requiring concurrent use of drugs or biologics with proarrhythmic potential.

Study Objectives This human Phase I trial involves taking the patient's own tumor cells during surgical craniotomy, treating them with an investigational new drug (an antisense molecule) designed to shut down a targeted surface receptor protein, and re-implanting the cells, now encapsulated in small diffusion chambers the size of a dime in the patient's abdomen within 24 hours after the surgery. Loss of the surface receptor causes the tumor cells to die in a process called apoptosis. As the tumor cells die, they release small particles called exosomes, each full of tumor antigens. It is believed that these exosomes as well as the presence of the antisense molecule work together to activate the immune system against the tumor as they slowly diffuse out of the chamber. This combination product therefore serves as a slow-release antigen depot. Immune cells are immediately available for activation outside of the chamber because a wound was created to implant these tumor cells and a foreign body (the chamber) is present in the wound. The wound and the chamber fortify the initial immune response which eventually leads to the activation of immune system T cells that attack and eliminate the tumor. By training the immune system to recognize the tumor, the patient is also protected through immune surveillance from later tumor growth should the tumor recur. Compared to the other immunotherapy strategies, this treatment marshalls the native immune system (specifically the antigen presenting cells, or dendritic cells) rather than engineering the differentiation of these immune cells and re-injecting them. Compared to traditional treatment alternatives for tumor recurrence, including a boost of further radiation and more chemotherapy, this treatment represents potentially greater benefit with fewer risks. This combination product serves as a therapeutic vaccine with an acceptable safety profile, which activates an anti-tumor adaptive immune response resulting in radiographic tumor regression. Conditions: Malignant Glioma of Brain Intervention / Treatment: DRUG: IGF-1R/AS ODN, DEVICE: biodiffusion chamber 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: * Failure after previous standard of care initial treatment of glioblastoma multiforme. * Documentation by MRI of an interval increase in nodular gadolinium enhancement consistent with recurrent malignant glioma suitable for therapeutic re-resection. * Previous pathological diagnosis of WHO Grade IV glioma. * All previous treatment interventions are acceptable. * Patients must have an ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1, or 2 or a KPS (Karnofsky Performance Score) of at least 60. * Patients must be 18 years of age or older. * Patients must sign an approved informed consent. * Hemodynamically stable, consistent with Standard of Care values for patients undergoing elective tumor resection. Exclusion Criteria: * Females who are pregnant, nursing, or not inclined to use adequate contraceptive methods if necessary to prevent pregnancy during the study. * An active second primary malignancy with the exception of basal cell or squamous cell skin carcinoma. * Major concomitant medical illness inclusive of severe chronic obstructive pulmonary disease, symptomatic coronary artery disease, heart failure, recent major cerebrovascular accident, brittle diabetes, renal dialysis, end stage liver disease, or labile hypertension. * Patients who have a history of heparin-induced thrombocytopenia or hypersensitivity to heparin, enoxaparin, or pork products. * Patients with an abnormal INR (International Normalized Ratio of greater than 1.3), if repeatable and refractory to correction by routine methods. * Patients who have documented deep venous thrombosis

Study Objectives This phase I trial studies the side effects and best dose of tipifarnib and erlotinib hydrochloride in treating patients with solid tumors that have spread to other places in the body. Tipifarnib and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Conditions: Solid Neoplasm Intervention / Treatment: DRUG: Erlotinib Hydrochloride, OTHER: Laboratory Biomarker Analysis, OTHER: Pharmacological Study, DRUG: Tipifarnib 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: * Histologic proof of cancer that is unresectable and for which no standard life-prolonging therapy is available * Absolute neutrophil count (ANC) >= 1500/uL * Platelet count (PLT) >= 100,000/uL * Total bilirubin =< 2 mg/dL * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) * Creatinine =< 1.5 x ULN * Hemoglobin (Hgb) >= 9.0 g/dL * Ability to provide informed consent * Willingness to return to Mayo Clinic Rochester for follow up * Life expectancy >= 12 weeks * At maximum tolerated dose (MTD) only: tumor that is amenable for serial biopsy * Medically capable and willing to provide the biologic specimens as required by the protocol Note: The goals of this study include assessment of the biologic effects on surrogate markers of the agent(s) being tested and are, therefore, contingent upon availability of the biologic specimens; patients with pre-existing clinical contraindications (e.g. anticoagulant therapy) for biopsy will be excluded from participation in the study; however, those patients who develop a major complication associated with the first biopsy (e.g. bleeding) or who develop clinical contraindications (e.g., anticoagulant therapy) after entry on study may remain on the study without the requirement for further tissue biopsies; this stipulation only applies to the 12 patients enrolled in Cohort II at MTD; the stipulation for provision of biologic specimens, as noted above, excludes the optional pharmacogenomic specimen Exclusion Criteria: * Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2, 3, or 4 * Uncontrolled infection * Any of the following prior therapies: * Chemotherapy =< 4 weeks prior to study entry * Mitomycin C/nitrosoureas =< 6 weeks prior to study entry * Immunotherapy =< 4 weeks prior to study entry * Biologic therapy =< 4 weeks prior to study entry * Hormonal cancer therapy =< 4 weeks prior to study entry * Radiation therapy =< 4 weeks prior to study entry * Radiation to > 25% of bone marrow * Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment * New York Heart Association classification III or IV * Patients on enzyme-inducing anticonvulsants (Phenobarbital, Dilantin, or Tegretol) * Any of the following: * Pregnant women * Nursing women * Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms plus spermicidal agents, diaphragm, birth control pills, injections, intrauterine device [IUD], or abstinence, etc.) * Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation) * Uncontrolled intercurrent illness including, but not limited to: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness/social situations that would limit compliance with study requirements * Prior treatment with EGFR targeting therapies (e.g., ZD-1869, EKB-569, OSI-774, CI-1033, GW572016, C225, EMD72000) or Farnesyl transferase inhibitors (R115777, SCH66336, BMS2146632) * Major surgery, or significant traumatic injury occurring =< 21 days prior to study entry * Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjögren's syndrome), congenital abnormality (e.g., Fuch's dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal-Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test) * Gastrointestinal tract disease resulting in an inability to take oral or nasogastric medication or a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease * Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy * Known brain metastases unless treated with surgery and/or radiation and stable for >= 8 weeks; patient should not be on enzyme-inducing anticonvulsants (Phenobarbital, Phenytoin (Dilantin) or Carbamazepine (Tegretol))

Study Objectives RATIONALE: Bafetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This clinical trial studies bafetinib in treating patients with recurrent high-grade glioma or brain metastases. Conditions: Adult Anaplastic Astrocytoma, Adult Anaplastic Ependymoma, Adult Anaplastic Oligodendroglioma, Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Adult Mixed Glioma, Recurrent Adult Brain Tumor, Tumors Metastatic to Brain, Adult Anaplastic Oligoastrocytoma Intervention / Treatment: DRUG: bafetinib, PROCEDURE: microdialysis, OTHER: pharmacological study, OTHER: liquid chromatography, OTHER: mass spectrometry, OTHER: laboratory biomarker analysis, GENETIC: protein expression analysis, GENETIC: western blotting, OTHER: immunohistochemistry staining method, PROCEDURE: therapeutic conventional surgery 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 radiographic findings consistent with either: * Recurrent high-grade glioma, or * Metastatic disease to the brain that has progressed after treatment with whole brain radiation therapy or stereotactic radiosurgery; patients who have a resectable brain metastasis as the only site of disease (i.e., no evidence of systemic disease), are not eligible to participate * Patients who are in need of a surgical debulking or a stereotactic biopsy for the purpose of diagnosis or differentiating between tumor progression versus treatment-induced effects following radiation therapy +/- chemotherapy will be eligible to participate in the microdialysis part of the study prior to beginning cycle 1 of bafetinib if the study neurosurgeon thinks there is a likelihood of being able to place the microdialysis catheter into residual tumor (enhancing brain tissue) * Patients who choose not to participate in the microdialysis part of the study may enroll in the study and start treatment at cycle 1 of bafetinib * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for 3 months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately * Patients must have a Karnofsky Performance Status (KPS) >= 60% * If corticosteroids are required for controlling cerebral edema, patients must be on a stable dose for at least 1 week prior to enrollment * Patients must not be taking any hepatic enzyme-inducing anticonvulsants (phenytoin, carbamazepine, phenobarbital, primidone, oxcarbazepine) for at least 2 weeks prior to enrollment * Absolute neutrophil count >= 1500 cells/mm^3 * Platelet count >= 100,000 cells/mm^3 * Total bilirubin =< 2.0 mg/dl * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 3 times the institutional upper limit of normal * Alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 3 times the institutional upper limit of normal * Serum creatinine =< 1.5 x the institutional upper limit of normal * QTc interval < 480 msec on electrocardiogram (ECG) * All subjects must have the ability to understand and the willingness to sign a written informed consent * Patients must have recovered from any toxicity of prior therapies (including brain radiation); an interval of at least 6 weeks must have elapsed since the completion of a nitrosourea-containing chemotherapy regimen; patients who have undergone a recent craniotomy cannot begin bafetinib until at least 2 weeks after the surgery Exclusion Criteria: * Patients who are currently receiving chemotherapy or are enrolled in another treatment clinical trial * Patients with a coagulopathy or bleeding disorder * Patients on anticoagulant drug therapy or medications that inhibit platelet function, such as ibuprofen or other non-steroidal anti-inflammatory drugs * Clinically evident congestive heart failure > class II of the New York Heart Association (NYHA) guidelines * Clinically significant cardiac arrhythmias * Patients taking a drug that can prolong the QT interval; if a potential study patient is taking one of the prohibited drugs but s/he can safely stop it, then a washout period of >= 7 days is required prior to starting bafetinib * History or signs of active coronary artery disease with or without angina pectoris * Patients who have a serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol or may not be able to comply with the safety monitoring requirements of the study * Human immunodeficiency virus (HIV)-positive patients receiving anti-retroviral therapy are excluded from the study due to the possibility of pharmacokinetic (PK) interactions with bafetinib; however, patients will not be routinely screened for HIV * Female patients who are pregnant or breast-feeding * Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals * Patients who have not recovered from the toxicities of prior chemotherapy or radiotherapy

Study Objectives Buprenorphine transdermal patch is newly available in Taiwan in June 2017, the trade name is Transtec, and the available dosages are 35 μg/h and 52.5 μg/h. Taiwan is the first Asia country which launched Transtec for cancer pain treatment. Although the efficacy of transdermal buprenorphine has been demonstrated in some randomized, placebo-controlled studies and also conducted a large scale post-marketing surveillance study in Germany, therefore the local scientific data is required for Asia experience. Due to above rationale, this observational study will be initiated in Taiwan, to build up the first real-world scientific data in Asia. The objective of this study is to collect the safety and effectiveness of transdermal buprenorphine in routine clinical practice, in particular, to collect data in population with controlled cancer pain and stable titration from previous opioid analgesics in Taiwan. Conditions: Cancer Intervention / Treatment: DRUG: Transdermal Buprenorphine Location: Taiwan Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * Cancer patients aged 20 years old and over * ECOG <3 * Moderate or severe pain intensity with stable titration from previous opioid analgesics, 7 days at least prior to enrolment and with the dose equivalent to oral morphine ranging from 60 to 120 mg/day in previous treatment * Cancer-related pain that requires treatment with continuous around-the-clock strong opioid analgesic * Patients who are going to start Transtec treatment per clinical judgment, according to the locally approved labeling, are eligible. * Patients who are able to communicate and fill out the questionnaire forms * Patient provided signed informed consent Exclusion Criteria: * Patients diagnosed with non-cancer pain or unexplained pain * Patients who have constipation (CTCAE grade 3 and above) * Patients with uncontrolled or unstable cardiac disease * Abnormal lab results, with obvious clinical significance, such as ALT or AST>= 3 fold of upper limit of normal value or liver function of Child C grade prior to study * ALT or AST >= 5 fold of upper limit of normal value for patients with liver metastasis or primary liver cancer * Pregnant or nursing (lactating) women * Patients who are drug or alcohol abuse * Patients who have hypersensitivity to buprenorphine * Patients who are clinically unstable or have a life expectancy of less than 8 weeks making completion of the trial unlikely * With any contraindications or using prohibited medication per locally approved

Study Objectives This prospective, randomized, single blinded study is designed to evaluate the postoperative analgesic efficacy of the ultrasound-guided subcostal transversus abdominis plane block in gastric cancer patients undergoing laparoscopic gastrectomy. We hypothesize that US guided subcostal TAP block with ropivacaine can significantly reduce postoperative opioid comparison in patients with laparoscopic gastrectomy. Conditions: Postoperative Pain Intervention / Treatment: PROCEDURE: Ultrasound guided subcostal transversus abdominis plane block (TAPB), DRUG: Ropivacaine 0.75% Injectable Solution, DEVICE: 21G 100 mm stimulator needle (Echoplex®, Vygon, Ecouen, France) Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Patients scheduled to undergo elective laparoscopic gastrectomy under general anesthesia * American Society of Anesthesiologists (ASA) physical classification I-III * Consent to IV-patient controlled analgesia use * Willingness and ability to sign an informed consent document Exclusion Criteria: * Do not understand our study * Allergies to anesthetic or analgesic medications * Wound infiltration analgesia for postoperative pain control * Infection or anatomic abnormality at the needle insertion site * Pregnancy/Breast feeder * Medical or psychological disease that can affect the treatment response

Study Objectives This clinical trial studies peripheral blood hemapoietic stem cell mobilization with the combination of bortezomib and G-CSF (filgrastim) in multiple myeloma and non-Hodgkin lymphoma patients. Conditions: Adult Grade III Lymphomatoid Granulomatosis, B-cell Chronic Lymphocytic Leukemia, Contiguous Stage II Adult Burkitt Lymphoma, Contiguous Stage II Adult Diffuse Large Cell Lymphoma, Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma, Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma, Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma, Contiguous Stage II Adult Lymphoblastic Lymphoma, Contiguous Stage II Grade 1 Follicular Lymphoma, Contiguous Stage II Grade 2 Follicular Lymphoma, Contiguous Stage II Grade 3 Follicular Lymphoma, Contiguous Stage II Mantle Cell Lymphoma, Contiguous Stage II Marginal Zone Lymphoma, Contiguous Stage II Small Lymphocytic Lymphoma, Cutaneous B-cell Non-Hodgkin Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Intraocular Lymphoma, Nodal Marginal Zone B-cell Lymphoma, Noncontiguous Stage II Adult Burkitt Lymphoma, Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma, Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma, Noncontiguous Stage II Adult Lymphoblastic Lymphoma, Noncontiguous Stage II Grade 1 Follicular Lymphoma, Noncontiguous Stage II Grade 2 Follicular Lymphoma, Noncontiguous Stage II Grade 3 Follicular Lymphoma, Noncontiguous Stage II Mantle Cell Lymphoma, Noncontiguous Stage II Marginal Zone Lymphoma, Noncontiguous Stage II Small Lymphocytic Lymphoma, Progressive Hairy Cell Leukemia, Initial Treatment, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Small Lymphocytic Lymphoma, Refractory Hairy Cell Leukemia, Refractory Multiple Myeloma, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, Stage I Adult Burkitt Lymphoma, Stage I Adult Diffuse Large Cell Lymphoma, Stage I Adult Diffuse Mixed Cell Lymphoma, Stage I Adult Diffuse Small Cleaved Cell Lymphoma, Stage I Adult Immunoblastic Large Cell Lymphoma, Stage I Adult Lymphoblastic Lymphoma, Stage I Grade 1 Follicular Lymphoma, Stage I Grade 2 Follicular Lymphoma, Stage I Grade 3 Follicular Lymphoma, Stage I Mantle Cell Lymphoma, Stage I Marginal Zone Lymphoma, Stage I Multiple Myeloma, Stage I Small Lymphocytic Lymphoma, Stage II Multiple Myeloma, Stage III Adult Burkitt Lymphoma, Stage III Adult Diffuse Large Cell Lymphoma, Stage III Adult Diffuse Mixed Cell Lymphoma, Stage III Adult Diffuse Small Cleaved Cell Lymphoma, Stage III Adult Immunoblastic Large Cell Lymphoma, Stage III Adult Lymphoblastic Lymphoma, Stage III Grade 1 Follicular Lymphoma, Stage III Grade 2 Follicular Lymphoma, Stage III Grade 3 Follicular Lymphoma, Stage III Mantle Cell Lymphoma, Stage III Marginal Zone Lymphoma, Stage III Multiple Myeloma, Stage III Small Lymphocytic Lymphoma, Stage IV Adult Burkitt Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Mixed Cell Lymphoma, Stage IV Adult Diffuse Small Cleaved Cell Lymphoma, Stage IV Adult Immunoblastic Large Cell Lymphoma, Stage IV Adult Lymphoblastic Lymphoma, Stage IV Grade 1 Follicular Lymphoma, Stage IV Grade 2 Follicular Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Mantle Cell Lymphoma, Stage IV Marginal Zone Lymphoma, Stage IV Small Lymphocytic Lymphoma, Untreated Hairy Cell Leukemia, Waldenström Macroglobulinemia Intervention / Treatment: DRUG: bortezomib, BIOLOGICAL: filgrastim, PROCEDURE: autologous hematopoietic stem cell transplantation Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Voluntary written informed consent form before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care * Diagnosis of B-type NHL or with multiple myeloma and eligible for autologous transplantation * No more than 3 prior regimens of chemotherapy (Rituximab is not considered chemotherapy) and 4 weeks out of Bortezomib treatment for MM * Karnofsky performance status of > 50% * The patient has recovered from all acute toxic effects of prior chemotherapy * White blood cell (WBC) > 3.0 x 10^9/L * Absolute neutrophil count > 1.5 x 10^9/L * Platelet count > 100 x 10^9/L * Serum creatinine =< 2.2 * Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT) less than two times the upper limit of normal (ULN) * Total bilirubin less than two times the ULN * Left ventricle ejection fraction > 50% (by normal echocardiogram [ECHO] or multi gated acquisition scan [MUGA] scan) * Diffusing capacity of the lung for carbon monoxide (DLCO) > 50% * Forced vital capacity > 50% of predicted * Negative for human immunodeficiency virus (HIV) * Female subject is either post-menopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential , agree to use 2 effective methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) from the time of signing the informed consent form through 30 days after the last dose of Bortezomib, or agree to completely abstain from heterosexual intercourse; women of child bearing potential agree to use an approved form of contraception; male subject, even if surgically sterilized (i.e., status post-vasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse for the duration of the study Exclusion Criteria: * Patient has a platelet count of < 100x 10^9/L within 14 days before enrollment * Patient has an absolute neutrophil count of ANC <1.5 x 10^9/L within 14 days before enrollment * Patient has creatinine of > 2.2 MG/DL within 14 days before enrollment * Patient has > 1.5 x ULN total bilirubin * Patient has >= grade 2 peripheral neuropathy within 14 days before enrollment * Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant * Patient has hypersensitivity to Bortezomib, boron or mannitol * Female subject is pregnant or breast-feeding; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (b-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women * Participation in clinical trials with other investigational drugs not included in this trial, within 14 days before enrollment and throughout the duration of this trial * Serious medical or psychiatric illness likely to interfere with participation in this clinical study * A co-morbid condition which, in the view of the investigators, renders the patient at high risk for this study * An acute medical condition resulting from prior chemotherapy * Brain metastases or carcinomatous meningitis * Acute infection * Fever (temp > 38 degrees Celsius [C]/100.4 degrees Fahrenheit [F]) * Patients of child-bearing potential unwilling to implement adequate birth control * Patients who have deterioration of their clinical status or laboratory parameters between the time of enrollment and transplant (such that they no longer meet entry criteria) may be removed from study at the discretion of the treating physician or principal investigator * Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy * Radiation therapy within 3 weeks before randomization; enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy

Study Objectives This phase I trial studies the best dose and side effects of TAK-659 and paclitaxel in treating patients with advanced solid tumors. TAK-659 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving TAK-659 and paclitaxel may work better in treating patients with advanced solid tumors. Conditions: Advanced Malignant Solid Neoplasm, Ovarian Carcinoma, Refractory Malignant Solid Neoplasm, Refractory Ovarian Carcinoma Intervention / Treatment: DRUG: Mivavotinib, DRUG: Paclitaxel, OTHER: Pharmacokinetic 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: * All patients have advanced malignancy, including but not limited to high-grade epithelial ovarian cancer or cancer harboring K-RAS mutation, either refractory to standard therapy or for which no effective standard therapy is available * Patients must have measurable or evaluable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 and life expectancy of greater than 3 months and/or other performance status of 0 to 1 * Female patients who: * Are postmenopausal for at least 1 year before the screening visit, OR * Are surgically sterile, OR * If they are of childbearing potential, agree to practice 1 highly effective method of contraception and one additional effective (barrier) method at the same time, from the time of signing the informed consent through 180 days after the last dose of study drug, OR * Agree to practice true abstinence, when is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together) * Agree not to donate eggs (ova) during the course of this study or 180 days after receiving their last dose of study drug * Male patients, even if surgically sterilized (i.e., status post-vasectomy), who: * Agree to practice effective barrier contraception during the entire study treatment period and through 180 days after the last dose of study drug, or * Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception. Female and male condoms should not be used together.) * Agree not to donate sperm during the course of this study or within 180 days after receiving their last dose of study drug * Absolute neutrophil count (ANC) >= 1,500/uL * Platelet count >= 100,000/uL (red blood cell count [RBC] and platelet transfusion allowed >= 14 days before assessment) * Hemoglobin >= 8 g/dL (RBC and platelet transfusion allowed >= 14 days before assessment) * Total bilirubin =< 1.5 x the upper limit of the normal range (ULN) (except patients with Gilbert's syndrome, who must have a total bilirubin =< 3.0 mg/dL) * Aminotransferases alanine (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN or =< 5 x ULN if hepatic metastasis * Serum creatinine =< 1 x ULN and creatine clearance >= 60 mL/min either as estimated by the Cockcroft-Gault equation or based on urine collection (12 or 24 hours) if serum creatinine is abnormal * Lipase =< 1.5 x ULN with no clinical symptoms suggestive of pancreatitis or cholecystitis * Amylase =< 1.5 x ULN with no clinical symptoms suggestive of pancreatitis or cholecystitis * Blood pressure =< grade 1 (hypertensive patients are permitted if their blood pressure is controlled to =< grade 1 by hypertensive medications and glycosylated hemoglobin is =< 6.5%) * Recovered (=< grade 1 toxicity) from the reversible effects of prior anticancer therapy * Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care * Patients may receive palliative radiation therapy immediately before or during the treatment if the radiation therapy is not delivered to the sole target lesions * Patients must be able to take oral medications without medical history of malabsorption or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the study agents * Patients have prior therapy with a taxane * Patients agree to provide archival tissue block or 10 formalin-fixed paraffin-embedded (FFPE) slides paraffin for use in pharmacodynamics correlative studies Exclusion Criteria: * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure (New York Heart Association [NYHA] Class III or IV), or history of myocardial infarction, unstable angina, stroke or transient ischemic attack within 6 months prior to study enrollment * Active brain metastases or leptomeningeal metastases * Known hypersensitivity (eg, anaphylactic and anaphylactoid reactions) to any particular combination drug will result in a patient being ineligible for inclusion in that particular cohort * History of drug-induced pneumonitis requiring treatment with steroids; history of idiopathic pulmonary fibrosis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted * Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on day 1 before first dose of study drug * Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol * Life-threatening illness unrelated to cancer that could, in the investigator's opinion, make the patient not appropriate for this study * Known human immunodeficiency virus (HIV) positive * Known hepatitis B surface antigen positive, or known or suspected active hepatitis C infection * Any treatment specific for systemic tumor control within 3 weeks prior to the initiation of the study drugs; or within 2 weeks if cytotoxic agents were given weekly (within 6 weeks for nitrosoureas or mitomycin C), or within 5 half-lives for targeted agents with half-lives and pharmacodynamic effects lasting less than 4 days (that includes but is not limited to erlotinib, sorafenib, sunitinib, bortezomib, and other similar agents), or failure to recover from toxic effects of any therapy prior to the study drug treatment * Any clinically significant comorbidities, such as uncontrolled pulmonary disease, known impaired cardiac function or clinically significant cardiac disease (specified below), active central nervous system (CNS) disease, active infection, or any other condition that could compromise the patient's participation in the study. Patients with any of the following cardiovascular conditions are excluded: * Acute myocardial infarction within 6 months before starting study drug * Current or history of New York Heart Association Class III or IV heart failure * Evidence of current, uncontrolled cardiovascular conditions including cardiac arrhythmias, angina, pulmonary hypertension, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities * Fridericia corrected QT interval (QTcF) > 450 milliseconds (msec) (men) or > 475 msec (women) on a 12-lead electrocardiogram (ECG) during the screening period * Abnormalities on 12-lead ECG including, but not limited to, changes in rhythm and intervals that, in the opinion of the investigator, are considered to be clinically significant * Use or consumption of any of the following substances: * Medications or supplements that are known to be inhibitors of P-glycoprotein (gp) and/or strong reversible inhibitors of CYP3A within 5 times the inhibitor half-life (if a reasonable half-life estimate is known), or within 7 days (if a reasonable half-life estimate is unknown), before the first dose of study drug. In general, the use of these agents is not permitted during the study except in cases where an adverse event (AE) must be managed * Medications or supplements that are known to be strong CYP3A mechanism-based inhibitors or strong CYP3A inducers and/or P-gp inducers within 7 days, or within 5 times the inhibitor or inducer half-life (whichever is longer), before the first dose of study drug. In general, the use of these agents is not permitted during the study except in cases where an AE must be managed * Grapefruit-containing food or beverages within 5 days before the first dose of study drug. Note that grapefruit-containing food and beverages are not permitted during the study * Major surgery within 14 days before the first dose of study drug and not recovered fully from any complications from surgery * Systemic infection requiring parenteral antibiotic therapy or other serious infection (bacterial, fungal or viral) within 21 days before the first dose of study drug. Patients who are at substantial risk of developing an infection may receive prophylaxis at the study of study treatment per investigator's discretion * Active secondary malignancy that requires treatment. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection and are considered disease-free at the time of study entry * Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-659 including difficulty swallowing tablets or diarrhea > grade 1 despite supportive therapy. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment * Patients with clinical bleeding, active gastric or duodenal ulcer * Grade 2 or higher peripheral neuropathy * Left ventricular ejection fraction (LVEF) is less than 50% on echocardiography (ECHO) or multiple-gated acquisition (MUGA) scanning or QTc is greater than 450 milliseconds (msec) for men and greater than 475 msec for women at screening * Treatment with high-dose corticosteroids for anticancer purposes within 14 days before the first dose of TAK-659; daily dose equivalent to 10 mg oral prednisone or less is permitted. Corticosteroids for topical use or in nasal spray or inhalers, or for premedication for paclitaxel are allowed * Lack of suitable venous access for the study-required blood sampling * Grade 2 or higher ophthalmologic disease

Study Objectives The purpose of this study is to establish the pharmacokinetics of PEG-Intron, administered at a dose of 6 μg/kg/week for 8 weeks (induction treatment), followed by a dose of 3 μg/kg/week for up to 252 weeks (maintenance treatment), in patients with high risk melanoma. Conditions: Melanoma Intervention / Treatment: DRUG: PEG-Intron Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Subjects at least 18 years of age, of either sex, and of any race. * Cytologically or histologically-confirmed melanoma, arising from a cutaneous or unknown site of origin, at Stages IIB, IIC, IIIA, IIIB, IIIC according to the American Joint Committee on Cancer (AJCC) 2001 guidelines. * Adequate hepatic, renal and bone marrow function within 4 weeks prior to initiation of study treatment. * Subjects presenting with synchronous primary and regional melanoma must have had adequate surgical margins surrounding the primary lesion. * Full lymphadenectomy must be performed within 90 days prior to initiation of study treatment. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Give informed consent according to International Conference on Harmonisation - Good Clinical Practice (ICH-GCP) and national/local policy. * Be able to adhere to dose and visit schedules. * Female subjects of childbearing potential must be using a medically accepted method of birth control prior to Screening and agree to continue its use during the study or be surgically sterilized. * Female subjects of childbearing potential must have a negative serum pregnancy test at Screening. Exclusion Criteria: * Female subjects who are pregnant, intend to become pregnant, or are breastfeeding. * Previous treatment with interferon alpha, chemotherapy or immunotherapy for melanoma. * Ocular melanoma, or melanoma of the mucous membranes. * Evidence of distant or non-regional lymph node metastases. * In-transit melanoma, even if the lesion has been resected. * Disease that cannot be completely surgically resected. * Lack of recovery from recent surgery. * Prior malignancy within the past 5 years, except surgically cured squamous cell carcinoma of the skin, successfully resected early stage cutaneous melanoma, or cervical carcinoma in situ. * Severe cardiovascular disease. * Thyroid dysfunction not responsive to therapy. * Uncontrolled diabetes mellitus (in the opinion of the investigator). * Active autoimmune disease. * Active and/or uncontrolled infection. * History of seropositivity for human immunodeficiency virus (HIV). * Pre-existing psychiatric condition. * Clinical diagnosis of substance abuse of one or more of the following drugs within the following timeframes (excluding time spent in detoxification, hospitalization or incarceration): * Alcohol, intravenous drug use, inhalational, psychotropics, narcotics, cocaine, prescription or over-the-counter drugs: within 1 year of the Screening visit. * Methadone, buprenorphine hydrochloride (HCl), and/or butorphanol tartrate: within 1 year of Screening visit, unless subject has drug screen negative for other (non-narcotic) drugs documented in the past year and repeated negative within 2 months of Screening visit. * Multi-drug abuse (2 or more substances in 16a and 16b): within 3 years of Screening visit. * Marijuana: * If historic use is deemed excessive by the principal investigator (or medically qualified individual), or is interfering with the subject's life, then the subject is not eligible and should not be screened. * If marijuana use is not deemed excessive by principal investigator and does not interfere with life, subject must discontinue any current use of marijuana prior to entry into study. * Medical condition requiring chronic systemic corticosteroids. * Known allergy to the drug substance or any of the excipients in the PEG-Intron formulation. * Any situation or condition that, in the opinion of the investigator, may interfere with optimal participation in the study. * Use of any investigational drugs within 30 days of study entry. * Participation in other clinical studies of investigational treatments.

Study Objectives This is a first-in-human (FIH), open-label, phase 1 dose-escalation study of KN026 in subjects with HER2 positive advanced breast and Gastric Cancer. The standard "3 + 3" design was used for dose escalation. There are 5 proposed dose levels which are 5, 10, 15, 20 and 30 mg/kg, but dosing interval may be adjusted during the study (such as QW, OR Q2W, OR Q3W) based on emerging data from this trial and/or from phase 1 trial of KN026 in other country. Dose escalation will continue until the maximum tolerated dose (MTD) is reached or if MTD is not found, dose escalation will continue until the MAD of 20 mg / kg is reached. Dose expansion will carried out in 20 mg/kg Q2W and 30 mg/kg Q3W. Conditions: Breast Cancer, Gastric Cancer Intervention / Treatment: DRUG: KN026 Location: China 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 subject >= 18 years and =<75 years. * Histologically or cytologically confirmed, locally advanced unresectable or metastatic breast cancer or gastric cancer. * ECOG score 0 or 1. * Life expectancy >3 months. * According to the definition of RECIST1.1, the patient has at least one measurable lesion. * Adequate organ function prior to start treatment with KN026. * Able to understand, voluntarily participate and willing to sign the ICF. * Subjects (women of child-bearing potential and males with fertile female partner) must be willing to use viable contraception method. Exclusion Criteria: * Accepted any other anti-tumor drug therapies within 4 weeks before fist dose. * Accepted radiotherapy within 4 weeks before enrollment(Subjects are eligible, which accepted palliative therapies within 2 weeks before the first dose of KN026 for osseous metastatic and all the AEs recovered). * An anthracyclines antibiotic treatment, such as doxorubicin (Adriamycin) was received exceeding 300 mg/m² within 90 days before first KN026 dosing, or other equivalent dose antharcyclines. * Subjects are eligible with clinically controlled and stable neurologic function >= 4 weeks, which is no evidence of CNS disease progression; Subjects with spinal cord compression and cancerous meningitis are not eligible. * Pregnant or nursing females；or intend pregnancy within this study period or within 6 monthes after the end of this study. * Has not recovered (ie, >Grade 1) from AEs except alopecia and anemia. * History of immunodeficiency, including HIV positive or other acquired, congenital immunodeficiency disease, or a history of organ transplantation. * Severe chronic and active infection, need to system antibiosis/antiviral treatment. * Cavity effusion (pleural effusion, ascites, pericardial effusion, etc.) are not well controlled, and need locally treatment or repeated drainage. -

Study Objectives Colorectal cancer is among the top three types of cancer that are most common and causes death worldwide.Nutritional support is widely used in elective colorectal surgery patients, as nutritional status is an important factor affecting clinical outcomes. European Society for Clinical Nutrition and Metabolism (ESPEN, 2016) emphasizes that nutritional supplementation with compounds such as amino acids, arginine, glutamine, and fish oil (omega 3) improves postoperative recovery. Glutamine; it becomes an essential amino acid under stress. It is an energy substrate for cells such as intestinal mucosal cells and lymphocytes, a material for glutathione synthesis, and a potent antioxidant, which also increases heat shock protein expression. In stressful conditions, arginine is the primary fuel source for T cells and is required for nitric oxide synthesis; therefore, it helps maintain immune function. Omega 3; It plays a role in the treatment of inflammation and improves wound healing. In addition, EPA and DHA increase the immune response by improving lymphocyte function. RNA; They are essential for maturation, proliferation, and function in nearly all biochemical processes, in rapidly proliferating cells such as T cells. studies have shown that immunonutrition (IMN) formulas enriched with biologically active compounds may be more effective in reducing infection complications and shortening postoperative hospital stays. This study aimed to investigate the additional effects of perioperative compared with preoperative immunonutrition on anthropometric, nutritional, and biochemical parameters, complications, and the length of hospital stay in patients with colorectal cancer. Conditions: Colorectal Cancer Intervention / Treatment: DIETARY_SUPPLEMENT: Preoperative Immunonutrition, DIETARY_SUPPLEMENT: Perioperative Immunonutrition Location: Turkey Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Diagnosed with colorectal cancer, * from 18 years up to 65 years old, * To be volunteer, * Informed written consent Exclusion Criteria: * Under the age of 18, * Above the age of 65 * To be pregnant, * Acute and chronic renal failure, cirrhosis, advanced COPD, mechanical intestinal obstruction, metastasis, presence of sepsis, * The ejection fraction is below 35%.

Study Objectives To determine the maximum tolerated dose of the drug temsirolimus given with radiation therapy for patients with non-small cell lung cancer. Conditions: Carcinoma, Non-Small-Cell Lung Intervention / Treatment: DRUG: Temsirolimus, RADIATION: Radiation therapy 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 must have a histologically or cytologically confirmed diagnosis of NSCLC. * Patients must have an indication for thoracic radiation. * Because all patients will be receiving radiation therapy to a thoracic mass, they must have radiographically measurable disease to participate. * Patients may not be candidates for definitive chemoradiation with curative intent. * Prior treatment of lung cancer (chemotherapy, radiation therapy, and surgery) are allowed if completed at least 4 weeks prior and if all treatment related toxicities are resolved. * At least 18 years of age. * Life expectancy of > 12 weeks. * Eastern Cooperative Oncology Group (ECOG) performance status 0-2. * Patients must have adequate organ and marrow function as defined below: * leukocytes >=3,000/mcL * absolute neutrophil count >=1,500/mcL * platelets >=100,000/mcL * total bilirubin < 1.5 * AST(SGOT)/ALT(SGPT) <=2.5 X institutional upper limit of normal * creatinine within normal institutional limits OR * creatinine clearance >=60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal * The effects of temsirolimus on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she 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 prior treatment with temsirolimus. * Patients may not be receiving any other investigational agents. * Patients with symptomatic brain metastases. Known brain metastases are allowed if asymptomatic and previously treated. * Patients may not be receiving enzyme-inducing antiepileptic drugs (EIAEDs; e.g., phenytoin, carbamazepine, phenobarbital) nor any other CYP3A4 inducer such as rifampin or St. John's wort, as these may decrease temsirolimus levels. A partial list of agents which interact with cytochrome P450 (CYP3A) is found in Appendix B. Use of agents that potently inhibit CYP3A (and hence may raise temsirolimus levels), such as ketoconazole, is discouraged, but not specifically prohibited. Temsirolimus can inhibit CYP2D6, and may decrease metabolism (and increase drug levels) of drugs that are substrates for CYP2D6, such as codeine. The appropriateness of use of such agents is left to physician discretion. A list of drugs that may have potential interactions with CYP2D6 is found in Appendix B. If there is any doubt about eligibility based on concomitant medication, the Principal Investigator should be contacted. All concomitant medications must be recorded. * Patients with known hypersensitivity reactions to macrolide antibiotics (such as erythromycin, clarithromycin, and azithromycin). * 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. * Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated. * Patients having received prior thoracic radiation therapy directed to the tumor volume to be treated with radiotherapy on this protocol.

Study Objectives Clinical studies have shown that IV administration of anesthetics, lidocaine and ketamine with their anti-inflammatory properties, modulates the acute immune response associated with surgical tissue injury, and in this manner they are able to reduce postoperative pain. Lidocaine has anti-inflammatory effects on polymorphonuclear granulocytes, IL-6 and IL-8 cytokines, complement component C3a and IL-1ra in serum. Ketamine produces its anti-inflammatory effects by reducing CRP and IL-6 in serum and by inhibiting NF-kB, which regulates gene transcription responsible for the production of proinflammatory factors. Perioperative combinend IV administration of lidocaine and ketamine could have a more favorable anti-inflammatory effect compared to anesthetic given alone or with placebo. To investigate the effects of lidocaine and ketamine in patients undergoing abdominal surgery on: acute immune response following the level of proinflammatory factors in serum (CRP, IL-6, IL-8); postoperative pain management; recovery of bowel function; administration of opioids; reduction of total treatment costs; length of hospital stay (LOHS) A double-blind, placebo-controlled study will include 100 patients undergoing open colorectal surgery. Patients will be randomly assigned to one of four groups: lidocaine, ketamine, lidocaine-ketamine, and placebo. Lidocaine will be administered at a dose of 1.5 mg/kg prior to surgical incision followed by an infusion at a rate of 1.5-2 mg/kg/hr until the end of surgery. Ketamine will be administered at a dose of 0.5 mg/kg in a bolus prior to surgical incision followed by an infusion at a rate of 0.1-0.2 mg/kg/hr until the end of surgery. Bolus and continuous placebo infusion (0.9% NaCl) will be equally administered at the same dose as the aforementioned anesthetics until the end of the surgery. Proinflammatory markers in serum (CRP, IL-6, IL-8) will be measured before induction of anesthesia, then 12 hours and 36 hours following the completion of surgery. The intensity of pain will be measured using the VAS score 2 hours and 4 hours following surgery and every 12 hours the following days. The investigators will measure also the consumption of opioids during and after surgery, the length of stay in the ICU, where pain control and analgesics use will be measured, as well as recovery of bowel function. Conditions: Colorectal Cancer Intervention / Treatment: OTHER: Lidocaine, OTHER: Ketamine, OTHER: Lidocaine and Ketamine, OTHER: Placebo (0.9% NaCl) Location: Croatia Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: OTHER Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Elective Surgery * Expected duration of the operation > 2 hours Exclusion Criteria: * Patients <= 18 years of age * Patients with history of allergy to local anesthetics * Chronic opioid analgesic * Patients who are unwilling or unable to participate

Study Objectives The goal of this clinical research study is to learn if giving PEG-Alpha Interferon (PEG-Intron) and Sargramostim (GM-CSF) to patients receiving treatment with high dose Gleevec (imatinib mesylate) is more effective in treating CML in chronic phase than therapy with imatinib mesylate alone. Conditions: Leukemia, Myeloid, Chronic Intervention / Treatment: DRUG: Gleevec, DRUG: Peg-alpha interferon (Peg-Intron), DRUG: Sargramostim (GM-CSF) Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * Patients with Ph-positive CML in early chronic phase CML who have received no or minimal prior therapy, (<1 month of prior IFN-alpha (with or without ara-C) and/or Gleevec). * Eastern Cooperative Oncology Group (ECOG) performance of 0-2. * Adequate end organ function, defined as the following: total bilirubin < 1.5 x upper limit of normal (ULN), serum glutamate pyruvate transaminase (SGPT) < 2.5 x ULN, creatinine < 1.5 x ULN * Signed informed consent. Exclusion Criteria: * New York Heart Association (NYHA) cardiac class 3-4 heart disease. * Psychiatric disability (psychosis) * Pregnant or lactating females * Late chronic phase, accelerated or blastic phase

Study Objectives This is a phase II, multi-center study to determine the efficacy and safety of first-line CC-486 plus CHOP in patients with PTCL who have received no prior systemic therapy. The study has a sample size of 20, and follows two-stage minimax design for primary efficacy analysis. Conditions: Previously Untreated Peripheral T-cell Lymphoma Intervention / Treatment: DRUG: CC-486 Administration, DRUG: CHOP Administration 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 diagnosis of PTCL of the following subtypes: Nodal T-cell lymphoma with T-follicular helper (TFH) phenotype (tumor cells must express 2 or 3 TFH-related antigens, including PD1, CD10, BCL6, CXCL13, ICOS, SAP and CCR5)* Angioimmunoblastic T-cell lymphoma Follicular T-cell lymphoma PTCL/NOS, T-follicular helper (TFH) variant PTCL-NOS Anaplastic large cell lymphoma, ALK negative Anaplastic large cell lymphoma, ALK positive with IPI > 2 Adult T-cell leukemia / lymphoma * No prior systemic therapy for lymphoma * Measurable disease defined by a tumor mass >= 1.5 cm in one dimension and measurable in two dimensions * ECOG performance status <= 2 Exclusion Criteria: * Known central nervous system (CNS) involvement by lymphoma * Active viral infection with HIV or hepatitis type B or C (seropositive HBV patients are eligible if they are negative for HBV DNA by PCR and receive concomitant antiviral therapy). * Prior history of malignancies other than PTCL unless the patient has been disease free for >= 5 years from the signing of the ICF.

Study Objectives The primary purpose of this study is to evaluate the safety and tolerability of vitamin C (ascorbic acid) given by injection into the vein. The second and third purpose of conducting this study is to observe any evidence of tumor response to the vitamin C and compare the level of fatigue (weakness), pain control, ability to do things, and quality of life, before and after vitamin C is given. Conditions: Cancer Intervention / Treatment: DRUG: Ascorbic Acid 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: * Primary histological diagnosis of advanced solid tumors (stage 3 and 4) and measurable disease. * Disease must have progressed for which no available treatment provides clinical benefit. * 18 years of age or older. * No scheduled cancer therapy (chemotherapy, hormonal therapy, immune therapy, or radiation therapy) for three months after study entry, and the subject must have had their last therapy at least four (4) weeks prior to entry to this study. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. * Informed Consent - The patient must be willing and able to sign the informed consent prior to the start of the trial. * Willingness to comply with the weekly phone calls between office visits. * Willingness to undergo central line placement (e.g., port-a-catheter, central venous catheter, percutaneously inserted central catheter [PICC] line placement) and able to manage care of the entry site safely. * Patients must be able to take food orally or have peg tube for feeding. * Life expectancy of at least 3 months. Exclusion Criteria: * Glucose-6-phosphate dehydrogenase deficiency (G6PD) (a relative contraindication) * Renal insufficiency as evidenced by serum creatinine of >= 1.3 mg/dl or evidence of oxalosis by urinalysis. * Chronic hemodialysis. * Iron overload (a ferritin > 500 ng/ml). * Wilson's disease. * Compromised liver function with evidence of complete biliary obstruction or have a serum bilirubin of 2.0 or liver function tests (AST > 63, ALT > 95) exceeding 1.5 x the upper limit of normal. * Pregnant or lactating female. * Current tobacco use. * Evidence of significant psychiatric disorder by history or examination that would prevent completion of the study or preclude informed consent. * Aspirin use exceeding 325 mg per day. * Acetaminophen use exceeding 2 g per day. * Brain metastases that have not responded to therapy.

Study Objectives The purpose of this study is to provide continued access to ixazomib and/or lenalidomide to participants who are continuing to have clinical benefit and to continue collecting relevant safety data to monitor safety in participants with Newly Diagnosed Multiple Myeloma (NDMM) who are not eligible for stem cell transplant. Conditions: Multiple Myeloma Intervention / Treatment: DRUG: Ixazomib, DRUG: Placebo, DRUG: Dexamethasone, DRUG: Lenalidomide Location: Canada, Korea, Republic of, New Zealand, United States, Belgium, Russian Federation, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Male or female participants >= 18 years diagnosed with Multiple Myeloma according to standard criteria who have not received prior treatment for multiple myeloma. * Participants for whom lenalidomide and dexamethasone treatment is appropriate and who are not eligible for high-dose therapy followed by stem-cell transplantation (HDT-SCT) for 1 or more of the following reasons: * The participant is 65 years of age or older. * The participant is less than 65 years of age but has significant comorbid condition(s) that are, in the opinion of the investigator, likely to have a negative impact on tolerability of HDT-SCT. * Measurable disease as specified in study protocol. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. * Meet the clinical laboratories criteria as specified in the protocol. * Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence, and must also agree to ongoing pregnancy testing; must also adhere to the guidelines of the lenalidomide pregnancy prevention program. * Male participants who agree to practice effective barrier contraception or agree to practice true abstinence AND must adhere to the guidelines of the lenalidomide pregnancy prevention program. * Suitable venous access for the study-required blood sampling. * Must be able to take concurrent aspirin 70 mg to 325 mg daily (or enoxaparin if aspirin allergic). * Voluntary written consent. * Participant is willing and able to adhere to the study visit schedule and other protocol requirements. Exclusion Criteria: * Prior treatment for multiple myeloma with either standard of care treatment or investigational regimen. * Diagnosed and treated for another malignancy within 5 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. * Inability or unwillingness to receive antithrombotic therapy. * Female participants who are lactating or pregnant. * Major surgery or radiotherapy within 14 days before randomization. * Infection requiring intravenous antibiotics within 14 days before the first dose of study drug. * Central nervous system involvement. * Diagnosis of Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome. * Evidence of current uncontrolled cardiovascular conditions within 6 months prior to randomization, including: Uncontrolled hypertension, cardiac arrhythmias, or congestive heart failure; Unstable angina, or Myocardial infarction. * Systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin,itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort within 14 days before randomization in the study. * Active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive. * Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens (e.g., peripheral neuropathy that is Grade 1 with pain or Grade 2 or higher of any cause). * Psychiatric illness/social situation that would limit compliance with study requirements. * Known allergy to any of the study medications. * Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal (GI) procedure that could interfere with the oral absorption or tolerance of treatment. * Treatment with any investigational products within 60 days before randomization.

Study Objectives RATIONALE: Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying the side effects and the best dose of carfilzomib in treating patients with relapsed or refractory chronic lymphocytic leukemia(CLL),small lymphocytic lymphoma(SLL), or prolymphocytic leukemia (PLL). Conditions: B-cell Chronic Lymphocytic Leukemia, Hematopoietic/Lymphoid Cancer, Prolymphocytic Leukemia, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia Intervention / Treatment: DRUG: carfilzomib, OTHER: Cytokine Assessment, OTHER: Pharmacodynamic Studies, OTHER: Proteosome Inhibition Assessment, OTHER: Pharmacogenomic Studies 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: * Previously treated patients with a diagnosis of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or prolymphocytic leukemia (PLL) by NCI Criteria with intermediate or high risk B-Cell chronic lymphocytic leukemia (CLL)(Modified Rai stage) satisfying at least one of the criteria for active disease requiring treatment;patients with a history of Richter's transformation are eligible if they now have evidence of chronic lymphocytic leukemia (CLL) only, with < 10% large cells in the bone marrow * Massive or progressive splenomegaly and/or lymphadenopathy; or need for cytoreduction for stem cell transplant * Anemia (hemoglobin < 11 g/dl) or thrombocytopenia (platelets < 100 x 10^9/L) * Presence of weight loss > 10% over the preceding 6 month period * NCI grade 2 or 3 fatigue * Fevers > 100.5 °C or night sweats for greater than 2 weeks without evidence of infection * Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of less than 6 months * Creatinine Clearance (CrCl) > 15mL/min * Alanine aminotransferase (ALT) < 3X upper limit of normal (ULN) * Bilirubin =< 2 times the upper limit of normal, unless disease related * Platelets >= 20 x 10^9/L and absence of active bleeding * Patients must have an ECOG (Eastern Cooperative Oncology Group) performance status =< 2 * Patients must not have secondary cancers that result in a life expectancy of <2 years or that would confound assessment of toxicity in this study * Patients of all racial/ethnic groups are eligible for the study if they meet eligibility criteria outlined- * Patients must provide written informed consent Exclusion Criteria: * Absence of previously treated chronic lymphocytic leukemia (CLL) * Female subject that is pregnant or breastfeeding; women of childbearing potential and men must agree to use adequate contraception prior to study entry, duration of study participation,and 30 days following study completion; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately;confirmation that the subject is not pregnant must be established by a negative serum -human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women * Patients with congestive heart failure (CHF)in whom pre-treatment hydration would be prohibitive;New York Heart Association (NYHA) Class III/IV CHF is excluded * Patients who have had treatment for chronic lymphocytic leukemia (CLL) within 2 weeks, although palliative steroids are acceptable * Patient unable to give written informed consent * Failure to recover from toxicity of previous radiotherapy or chemotherapy to grade 1 * Patients with active infections requiring intravenous (IV) antibiotic/antiviral therapy are not eligible for entry onto the study until resolution of the infection; patients on prophylactic antibiotics or antivirals are acceptable * Patients who have previously taken bortezomib

Study Objectives This phase I trial studies the side effects and best dose of ABC294640 in treating patients with advanced solid tumors. ABC294640 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Please note that the FDA OOPD is participating as a funding source. Conditions: Pancreatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific Intervention / Treatment: DRUG: sphingosine kinase-2 inhibitor ABC294640 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: * PART I: * Patients with histologically confirmed solid organ carcinomas * Tumor progression after receiving standard/approved chemotherapy or as first-line therapy for malignancies where there is no standard therapy * One or more tumors measurable on computed tomography (CT) scan per RECIST 1.1 * Eastern Cooperative Oncology Group (ECOG) performance status =< 2 * Life expectancy of at least 3 months * Age > 18 years * Signed, written Institutional Review Board (IRB)-approved informed consent * A negative pregnancy test (if female) * Acceptable liver function: * Bilirubin =< 3 times upper limit of normal (ULN) (Common Terminology Criteria for Adverse Events [CTCAE] Grade 2 baseline) * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 3 x ULN (CTCAE Grade 1 baseline) * Serum creatinine =< 1.5 X ULN (CTCAE Grade 1 baseline) * Absolute neutrophil count >= 1000 cells/mm^3 * Acceptable hematologic status: * Absolute neutrophil coun > 1000 cells/mm3 * Platelet count >= 75,000 (plt/mm^3) (CTCAE Grade 1 baseline) * Hemoglobin >= 9 g/dL * Acceptable blood sugar control: * Fasting glucose value < 160 mg/dL (CTCAE Grade 1 baseline) * Urinalysis: No clinically significant abnormalities * Prothrombin time (PT) and partial thromboplastin time (PTT) =< 1.5 X ULN after correction of nutritional deficiencies that may contribute to prolonged PT/PTT * For men and women of child-producing potential, willingness to use of effective contraceptive methods during the study; if female (or female partner of male subject), is either not of childbearing potential (defined as postmenopausal for >= 1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy or hysterectomy]) or practicing 1 of the following medically acceptable methods of birth control and agrees to continue with the regimen throughout the duration of the study: * Oral, implantable or injectable contraceptives for 3 consecutive months before the baseline/randomization visit * Total abstinence from sexual intercourse (>= 1 complete menstrual cycle before the baseline/randomization visit) * Intrauterine device (IUD) * Double barrier method (condoms, sponge, diaphragm or vaginal ring with spermicidal jellies or cream) * PART II: * To be eligible for inclusion in Part II, patients must meet the eligibility for Part 1 as well as the following: * Patients with histologically confirmed HCC for whom there is no standard/approved chemotherapy Exclusion Criteria: * New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on electrocardiogram (ECG) * Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy * Pregnant or nursing women; NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately * Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within one month prior to study entry * Unwillingness or inability to comply with procedures required in this protocol * Known infection with human immunodeficiency virus (HIV) * Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor * Patients who are currently receiving any other investigational agent * Patients who are receiving drugs that are sensitive substrates of CYP450 1A2, 3A4, 2C9, 2C19 or 2D6, or strong inhibitors or inducers of all major CYP450 isozymes that cannot be stopped at least 7 days or 5 half-lives (whichever is longer) before starting treatment with ABC294640 and either replaced with another appropriate medication or not given for the duration of the clinical study * Patients who are currently taking Coumadin or Coumadin derivatives * Patients who have received any antineoplastic therapy within 1 month of starting treatment with ABC294640 or who have not adequately recovered from side effects and toxicities of previous antineoplastic therapy

Study Objectives The main objective of this multicenter, randomized, double-blind, placebo-controlled phase III trial is to assess the impact of maintenance orteronel on disease progression and hence on quality of life in patients with metastatic castration-resistant prostate cancer who have achieved at lease disease stabilization after first line chemotherapy with docetaxel. Conditions: Prostate Cancer Intervention / Treatment: DRUG: Orteronel, DRUG: Placebo Location: Switzerland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Patient has given voluntary written informed consent * Male patient >= 18 years * WHO performance status of <=2 * Adenocarcinoma of the prostate * Castration resistance: tumor progression after orchiectomy or during treatment with GnRH analogues * Metastatic disease, radiographically documented ( * Total testosterone <= 50 ng/dL * Non-progressive disease after docetaxel first-line treatment with a cumulative dose >= 300mg/m2 * No evidence of progression on imaging according to PCWG2 and modified RECIST 1.1 criteria * PSA levels not elevated >= 25% AND at least 2 ng/mL above the nadir since start of docetaxel treatment * Non-surgically castrated patient agrees on ongoing use of GnRH analogues (agonists or antagonists) during the trial * PSA >= 2 ng/mL; Potassium >= 3.5 mmol/L; Neutrophils >= 1.5 x 109/L; Platelets >= 100 x 10x9/L * Normal kidney and liver function * Planned start of trial treatment 3 to 6 weeks after last docetaxel administration * Screening calculated ejection fraction of >= 50% or normal according to local standard by echocardiogram or by multiple gated acquisition (MUGA) scan. * Baseline QL questionnaire completed * Patient is able and willing to swallow study drug as whole tablet * Patient compliance and geographic proximity allow proper staging and follow-up * Patient agrees to practice effective barrier contraception or to completely abstain from intercourse Exclusion Criteria: * Prior therapy with aminoglutethimide, ketoconazole, orteronel, abiraterone or other modern CYP17 inhibitors * Prior chemotherapy for prostate cancer within 12 months before enrollment except from docetaxel * Retreatment with docetaxel after interruption of > 5 weeks * Concurrent disease requiring higher doses of corticosteroid than the equivalent of 10 mg prednisone per day * Known hypersensitivity to trial drug or hypersensitivity to any of its components * Patient has received other investigational drugs within 30 days before enrollment * Presence of a small cell component in histological specimen * Radiotherapy within the last 2 weeks before expected start of the trial treatment * Known history of central nervous system (CNS) or spinal cord metastases * Current spinal cord compression * Diagnosed or treated for another malignancy within 2 years of registration, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, or any in situ malignancies * History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias of Grade >= 3 (NCI CTCAE version 4.0) or thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events) within 6 months prior to first dose of study drug. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed * New York Heart Association Class III or IV heart failure * ECG abnormalities of: * Q-wave infarction, unless identified >= 6 months prior to registration * QTc interval > 460 msec * Uncontrolled hypertension despite appropriate medical therapy * Likely inability (e.g. due to a psychiatric disorder) to understand information on trial related topics, to give informed consent, to comply with the protocol, to fill in QL forms and to cooperate fully with the investigator and site personnel * Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of orteronel * Known active chronic hepatitis B or C, life-threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with participation in this study

Study Objectives The purpose of this study is to determine if E7070 is an efficacious, safe, and tolerable treatment for patients with metastatic breast cancer who have failed, or could not tolerate, prior treatments with an anthracycline, a taxane, and capecitabine. Conditions: Breast Neoplasms, Metastases Intervention / Treatment: DRUG: E7070 Location: United States, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must be female, * Patients must have histologically or cytologically confirmed metastatic breast cancer, * Patients must either have tumors that are resistant/refractory to chemotherapy with an anthracycline, a taxane, capecitabine, and appropriate Herceptin therapy, or tumors that cannot be treated with these agents due to patient's treatment toxicity; therefore, patients must have received 2 prior chemotherapies but no more than 3 prior chemotherapies in the metastatic setting, * Patients must have at least one uni-dimensionally measurable lesion according to the RECIST criteria in at least one site that has not been irradiated, * Patients must be aged >= 18 years, * Patients must have a Karnofsky Performance Status of >= 70%, * Patients must have a life expectancy of >= 3 months, * Patients must have adequate renal function as evidenced by serum creatinine <= 1.5 mg/dL, or if > 1.5 but <= 1.8 mg/dL, then a creatinine clearance of >= 45 mL/min, * Patients must have adequate bone marrow function as evidenced by absolute neutrophil count of >= 1.5 x 109/L, hemoglobin >= 9.0 g/dL, and platelet count >= 100 x 109/L, * Patients must have adequate liver function as evidenced by bilirubin of <= 1.5 times the upper limits of normal (ULN); alkaline phosphatase <= 3 times ULN and alanine transaminase (ALT) and aspartate transaminase (AST) <= 3 times ULN, unless related to liver metastasis, in which case <= 5 x ULN, * Patients must have serum electrolytes including calcium (corrected for albumin), magnesium, and potassium (corrected) within normal limits, * Patients must be willing and able to complete the FACT-B questionnaire, * Patients must be willing and able to comply with the study protocol for the duration of the study, and * Patients must give written informed consent prior to any study specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice. Exclusion Criteria: * Patients must not have metastatic disease that can be completely surgically resected, * Patients who received adjuvant taxane must not have experienced disease progression within 12 months of beginning that therapy, * Patients must not have received chemotherapy, hormonal therapy, or Herceptin within 2 weeks of E7070 treatment start and must have recovered from any chemotherapy-related or other therapy-related toxicity at study entry, * Patients must not have received investigational drugs including immunotherapy, gene therapy, or other biologic therapy; antineoplastic therapy; or radiation therapy (other than required for palliation of bone pain or chest ulceration) within 2 weeks of E7070 treatment, * Patients must not have received prior treatment with Mitomycin C or nitrosoureas, * Patients must not have undergone high dose chemotherapy with hematopoietic stem cell rescue, * Patients must not have untreated brain metastases (Patients who have been treated for central nervous system (CNS) metastases must be asymptomatic and radiologically stable [not receiving radiation] and must not have been receiving steroids for 4 weeks prior to entry. Patients without known CNS metastases who are symptomatic for CNS metastasis must be evaluated with a CT scan or MRI scan prior to E7070 treatment.), * Patients must not have had major surgery without full recovery within 4 weeks of E7070 treatment start, * Patients must not have pulmonary lymphatic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen, * Patients must not have leptomeningeal metastasis, * Patients must not have evidence of clinically relevant ascites or pleural effusion requiring more than one isolated paracentesis or pleurocentesis per month prior to study start, * Patients must not be expected to require more than one isolated paracentesis or pleurocentesis per month during the study for the treatment of clinically relevant ascites or pleural effusion, * Patients must not be pregnant or breast-feeding and must practice adequate contraception if not surgically sterile, * Patients must not have severe medically uncontrolled intercurrent illness/infection, * Patients must not have had unstable angina or myocardial infarction in the past 6 months, * Patients must not have serious cardiac arrhythmia or symptomatic congestive heart failure >= Grade II (NYHA classification), * Patients must not have a history of prolonged QT, QTc > 470 ms (Bazett's correction) at entry, or history of torsade de pointes, * Patients must not have recent history (<= 12 months) of active or chronic viral hepatitis, * Patients must not have organ allografts, * Patients must not have known history of HIV positivity, * Patients must not have a history of hypersensitivity to sulfonamides, * Patients must not have a history of uncontrolled seizures, * Patients must not have had a prior malignancy, other than carcinoma in situ of the cervix or nonmelanoma skin cancer, unless the prior malignancy was diagnosed and definitively treated >= 5 years previously with no subsequent evidence of recurrence, or * Patients must not have other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the study.

Study Objectives This is an open-label, nonrandomized, Phase 1/2 study for the fibroblast growth factor receptor (FGFR) inhibitor futibatinib (TAS-120). The purpose of the study is to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic, and anti-tumor activity of futibatinib in patients with advanced solid tumors with and without genomic FGF/FGFR abnormalities. The study will be conducted in 3 parts: 1. Dose escalation portion to determine the -Maximum Tolerated Dose and/ or Recommended Phase 2 Dose of futibatinib. 2. Phase 1 expansion portion to further evaluate the safety and efficacy of futibatinib in patients with tumors harboring FGF/FGFR aberrations, including patients with cholangiocarcinoma (CCA), primary central nervous system tumors, urothelial carcinoma, breast cancer, gastric cancer. 3. Phase 2 study portion to confirm objective response rate of futibatinib in intrahepatic CCA patients with tumors harboring FGFR2 gene rearrangements (incl fusions). Conditions: Cholangiocarcinoma, Urothelial Cancer, Advanced and Metastatic Cancer Patients With Tumors Harboring FGF/FGFR Tumors, Primary CNS Tumors, Breast Cancer, Gastric Cancer Intervention / Treatment: DRUG: Futibatinib Location: Germany, Canada, Japan, Korea, Republic of, Italy, Netherlands, Spain, United Kingdom, United States, Australia, Taiwan, Hong Kong, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SEQUENTIAL Masking: NONE

Inclusion Criteria: * Provide written informed consent * Age >= 18 years of age * Has histologically or cytologically confirmed, locally advanced or metastatic cancer * The following specific criteria for each study portion Phase 1 (Dose Escalation): * Patients with any type of solid tumor * Disease progression following standard therapies or intolerant to prior standard therapies Phase 1 (Dose Expansion) * Have at least one FGF/FGFR aberration * Disease progression following standard therapies or were intolerant to prior standard therapies (including prior FGFR inhibitors). * Have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009) for advanced solid tumors or Response Assessment in Neuro-Oncology criteria (2010) for brain tumors. * Patients with any of the following tumor types * Patients with intrahepatic or extrahepatic CCA harboring FGFR2 gene fusions or other FGFR2 aberrations * Patients with primary CNS tumors * Patients with advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating mutations * Patients with breast cancer or gastric cancer * Patients with other solid tumor types harboring FGFR gene fusions or activating mutations * Patients with solid tumor types and other FGF/FGFR alterations not listed above Phase 2 * Patients with iCCA and FGFR2 gene rearrangements (incl fusions) * Have been treated with at least one prior systemic gemcitabine and platinum-based chemotherapy * Must have documentation of radiographic progression of disease * No prior FGFR inhibitor * Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009) * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Adequate organ function. Exclusion Criteria: * History and/or current evidence of clinically significant non-tumor related alteration of calcium-phosphorus homeostasis. * History and/or current evidence of clinically significant ectopic mineralization/calcification. * History and/or current evidence of clinically significant retinal disorder * A serious illness or medical condition(s) * Pregnant or breast-feeding female

Study Objectives The purpose of this study is to determine whether the treatment of locally advanced esophageal squamous cell carcinoma (ESCC)with cetuximab in combination with paclitaxel, cisplatin and radiation improve clinical outcomes. Conditions: Esophageal Cancer Intervention / Treatment: DRUG: cetuximab (Erbitux), DRUG: Paclitaxel, DRUG: Cisplatin, RADIATION: Radiation Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Inpatients or outpatients, >= 18 years of age * Histologically confirmed primary (non-recurrent) ESCC fulfilling one of the following criteria (AJCC Staging System) * cervical esophageal carcinoma, stage Ⅱ-Ⅲ * upper thoracic esophageal carcinoma, stage Ⅱ-Ⅲ, or mid-thoracic esophageal carcinoma, stage Ⅱ-Ⅲ,which is medically unfit for surgery, surgery been refused and patient medically able to tolerate chemo-radiation. * Evidence of unidimensional measurable disease as per Response Evaluation Criteria in Solid Tumours (RECIST). * ECOG Performance status of 0-1 * Effective contraception for both male and female patients if the risk of conception exists * Adequate bone marrow reserves: neutrophil (ANC) count >= 1500 /mm^3, platelet count >= 100,000 /mm^3, hemoglobin >= 9 g/dl * Adequate renal function: serum creatinine <= 1.5 mg/dl and/or calculated creatinine clearance >= 60 ml/min * Adequate hepatic function: bilirubin level <= 1.5 x ULN, ASAT & ALST <= 1.5 x ULN * Tumor tissue available for KRAS biomarker test * Signed written informed consent prior to study entry Exclusion Criteria: * Previous chest radiotherapy, systemic chemotherapy, and major esophageal surgery * Concurrent chronic systemic immune therapy, targeted therapy not indicated in this study protocol * Multiple primary carcinomas of the esophagus * Pregnancy (confirmed by serum or urine β-HCG) or lactation period; * Uncontrolled diabetes, hypertension, and severe cardiac or pulmonary disease * Unable to comprehend the study requirements or who are not likely to comply with the study parameters; * Distant metastasis * Second malignancy, except for curable non-melanoma skin cancer, cervical cancer in situ, or malignant disease, free for >= 5 years * Known grade 3 or 4 allergic reaction to any of the study treatment

Study Objectives The purpose of this study is to compare the effectiveness of two methods of treating cancer of the cervix. Half the patients will receive gemcitabine plus cisplatin while undergoing radiation therapy, followed by adjuvant gemcitabine and cisplatin and the other half will receive cisplatin along with radiation therapy without adjuvant therapy. Conditions: Cancer of Cervix Intervention / Treatment: DRUG: Gemcitabine, DRUG: Cisplatin, RADIATION: Brachytherapy, RADIATION: Pelvic radiation Location: Mexico, India, Thailand, Pakistan, Peru, Bosnia and Herzegovina, Argentina Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * diagnosed with cancer of cervix * tumor that can be measured * no previous treatment with chemotherapy or radiation for this cancer * Karnofsky Performance Status Score >=70 * able to give written consent * willing and able to participate in the study, both during the active treatment and the follow-up period. Exclusion Criteria: * impairment such as hearing loss from prior cisplatin therapy * damage to nerves such as being unable to distinguish hot and cold to touch * used other experimental medication in past 30 days * lab test results are not within the limits required for this study * pregnancy or breast-feeding or possibility of becoming pregnant during this study and not using an approved method of birth control.

Study Objectives To investigate the safety of Nivolumab in combination with Ipilimumab in subjects with previously untreated advanced or metastatic Renal Cell Cancer. Conditions: Renal Cell Carcinoma Intervention / Treatment: DRUG: Nivolumab, DRUG: Ipilimumab Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Type of Participant and Target Disease Characteristics * Advanced or metastatic RCC * Histologically confirmed, previously untreated (treatment-naive) RCC * No prior systemic therapy for RCC except for one prior adjuvant or neoadjuvant therapy for completely resectable RCC * Measurable disease as per RECIST 1.1. Subject must have extracranial metastasis as measurable disease * Karnofsky Performance Status (KPS) of at least 70% for Cohort 1, 2, and 3; KPS of 50-60% for Cohort 4 * Tumor tissue need be received by the central vendor (block or unstained slides). Note: Fine Needle Aspiration (FNA)and bone metastases samples are not acceptable for submission. Exclusion Criteria: * Medical Conditions 1. Subjects with any active autoimmune disease or a history of known autoimmune disease 2. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured 3. Known HIV or AIDS-related illness 4. Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection. * Prior/Concomitant Therapy 1. Prior systemic treatment in the metastatic setting with Vascular epithelial growth factor(VEGF) or VEGF receptor targeted therapy 2. Prior treatment with an anti-Programmed Death (PD) -1, anti-PD-L1, anti-PD-L2, anti-cluster of differentiation 137 (CD137), or anti-cytotoxic T-lymphocyte-associated antigen 4(CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. This includes the utilization of these agents in the neo-adjuvant or adjuvant setting. 3. Anti-cancer therapy less than 28 days prior to the first dose of study drug or palliative, focal radiation therapy less than 14 days prior to the first dose of study drug. Other protocol defined inclusion/exclusion criteria apply

Study Objectives This trial is part of a larger, longitudinal study of symptoms that occur in the breast surgical scar area and/or ipsilateral arm following breast cancer surgery. Women who develop pain in the breast scar area or ipsilateral arm will be randomized to a placebo patch or a lidocaine patch that they will wear on a daily basis for 12 weeks. We hypothesize that women who wear the lidocaine patch will report a decrease in pain and decreased interference with function compared to women who wear the placebo patch. Conditions: Neuropathic Pain, Postmastectomy Pain Intervention / Treatment: DRUG: Lidoderm patch, DRUG: Placebo patch Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Adult women >18 years who develop neuropathic pain in the breast scar area and/or ipsilateral arm following breast cancer surgery * Has a healed incision(s) * Has no recurrent disease in the painful area * Is able to read, write and understand English Exclusion Criteria: * Presence of another type of pain that is more severe than the neuropathic pain * Use of an opioid analgesic of greater than 60 mg codeine/day * Is actively trying to become pregnant * Has a medical contraindication to the use of lidocaine * Has an allergy to lidocaine * Is taking a coanalgesic for neuropathic pain.

Study Objectives The primary objective of this study is aimed at analyzing the ICU triage practices of clinicians at a cancer hospital with and without the use of an algorithm-based triage tool, and to assess whether or not the triage tool improves the consensus amongst practioners on the prioritization of patients for ICU admission. Secondary objectives include assessment of whether or not triage practices based on guidelines correlate with what is done in actual practice. Conditions: Intensive Care Units, Triage Intervention / Treatment: BEHAVIORAL: Survey, BEHAVIORAL: Algorithm-based Triage Tool Location: United States, Ecuador Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: OTHER Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: 1) Study participant must be a health care provider who frequently refers or accepts oncologic patients to the ICU Exclusion Criteria: 1) none

Study Objectives A Randomized, double-blind, placebo-controlled, multi-center Phase 3 study evaluating efficacy, safety and pharmacokinetics of Trilaciclib In Extensive-Stage Small Cell Lung Cancer Patients Receiving Carboplatin combined with Etoposide or Topotecan The study consists of 2 parts: Part 1: safety run-in and pharmacokinetics evaluation of 12 ES-SCLC patients (6 each for first line and second/third line ES-SCLC patients); Part 2: randomized, double-blind, placebo-controlled efficacy confirmation study of 80 ES-SCLC patients (stratified by first line and second/third line ES-SCLC, ECOG PS \[0-1 vs 2\] and brain metastases. The study includes screening period, treatment period, safety follow-up and survival follow-up. Conditions: Extensive-stage Small-cell Lung Cancer Intervention / Treatment: DRUG: Trilaciclib Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Male or female of >= 18 years old; * Histology or cytology diagnosed extensive-stage small cell lung cancer ( ES-SCLC ) : * Patients who plan to receive carboplatin combined with etoposide: naïve with systemic treatment (such as chemotherapy or combined immunotherapy) in the past * Patients planning to receive topotecan : previously received 1/2 line chemotherapy or combined immunotherapy except for topotecan. * At least one measurable lesion without radiotherapy that meets RECIST1.1 standard; * Hemoglobin >= 90 g/L ; * Neutrophil count >= 1.5 × 109 /L ; * Platelet count >=100 × 109 /L ; * Creatinine <= 15 mg /L or creatinine clearance (CrCl) >= 60 mL/min (Cockcroft-Gault formula ) ; * Total bilirubin <= 1.5 × upper limit of normal (ULN) ; * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 3 × ULN or <= 5 × ULN (patients with liver metastases) ; * Albumin >= 30 g/L ; * ECOG PS score:0-2 ; * Expected survival time >= 3 months ; * Contraception : * Women: Women with potential fertility must have a negative serum pregnancy test result at Screening, and take reliable contraceptive measures from signing informed consent to 3 months after the last administration ; * Male: If a female partner has potential fertility, reliable contraceptive measures must be taken after signing the informed consent to 3 months after the last administration. * Understand and sign the informed consent form. Exclusion Criteria: * Symptomatic brain metastases that require local radiotherapy or hormone therapy; * Other history of malignant cancer, except for: (1) clinically cured basal cell or squamous cell tumors; (2) curable: a) cervical cancer, B) prostate cancer, C) superficial bladder cancer; or ( 3 ) any solid tumor that it is clinically cured for 3 years or above; * Uncontrolled ischemic heart disease or congestive heart failure with clinically significance (NYHA Class III or IV) ; * Stroke or cardiovascular and cerebrovascular events within 6 months before enrollment ; * Severe active infection; * Potential inadequate compliance from psychological or other social factors; * Other uncontrolled severe chronic disease or condition, which considered by Investigator as unsuitable for study participation; * Known HIV infection, active hepatitis B (defined as HBV DNA positive) and hepatitis C (HCV RNA positive); * Received radiotherapy within 2 weeks before enrollment ; * Received cytotoxic or investigational drug treatment within 4 weeks, or non-cytotoxic anti-tumor treatment within 2 weeks before enrollment; * For Part 1 patients, concomitant administration of strong or moderate inducer of CYP3A4 within 4 weeks before study drug, or strong inhibitor of CYP3A4 within 2 weeks before study drug; * Recovery from previous toxicity of anti-tumor treatments to Level 0 or 1 (except for hair loss); * Allergy to the study drugs or any of their components (Trilaciclib, etoposide, carboplatin, topotecan); * Unable to act independently by legal restrictions or in the legal sense; * Women who are pregnant or breastfeeding ; * Other patients who are considered unsuitable to participate in the study. -

Study Objectives This is an open-label, phase 2 non-comparative study to assess the safety, tolerability, and preliminary efficacy of nal-IRI in combination with other anticancer therapies in patients not previously treated for metastatic pancreatic adenocarcinoma. This study will assess the following regimen: • nal-IRI + 5-fluorouracil (5-FU)/leucovorin (LV) + oxaliplatin The study will be conducted in two parts: Part 1, consisting of an initial dose exploration (Part 1A) followed by dose expansion (Part 1B) of the irinotecan liposome injection +5-FU/LV + oxaliplatin regimen and Part 2, consisting of a comparison of irinotecan liposome injection-containing regimen versus nab-paclitaxel plus gemcitabine. The comparative Part 2 was removed in a protocol amendment, dated 11 April 2018 (Version 6.0), before it was initiated, as this comparative part of the study is being undertaken as a stand-alone phase III study D-US-60010-001. This CSR only pertains to the single-arm dose exploration and dose expansion Part 1 results and no further reference is made to the comparative Part 2. Conditions: Pancreatic Cancer Intervention / Treatment: DRUG: nal-IRI, DRUG: 5 fluorouracil, DRUG: Leucovorin, DRUG: Oxaliplatin Location: United States, Spain, Australia 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 the pancreas that has not been previously treated in the metastatic setting * Unresectable, locally advanced or metastatic disease; diagnosed within 6 weeks prior to screening * At least one tumor lesion measurable by CT or MRI scan (according to RECIST v1.1) * ECOG performance status of 0 or 1 at screening and within 72 hours prior to first dose if first dose occurs more than 72 hours post-screening * Adequate hematological, hepatic, renal and cardiac function * Recovered from the effects of any prior surgery or radiotherapy * Patient has a Karnofsky performance status (KPS) >= 70 at Screening, and within 72 hours prior to date of first dose if first dose occurs more than 72 hours after screening (Part 1B only) Exclusion Criteria: * Prior treatment of pancreatic cancer in the metastatic setting (or locally advanced setting) with surgery (placement of stent is allowed), radiotherapy, chemotherapy or investigational therapy * Prior treatment of pancreatic cancer with chemotherapy in adjuvant setting, except those where at least 12 months have elapsed since completion of the last dose and no persistent treatment-related toxicities present * Uncontrolled Central Nervous System (CNS) metastases * Clinically significant gastrointestinal disorder * History of any second malignancy in the last 3 years. Patients with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible * Presence of any contraindications for nal-IRI, irinotecan, 5-FU, leucovorin, oxaliplatin * Use of strong CYP3A4 or inducers or presence of any other contra indications for irinotecan * Pregnant or breast feeding * Neuroendocrine or acinar pancreatic carcinoma * Serum albumin < 3 g/dL at screening visit and within 72 hours prior to first dose if first dose occurs more than 72 hours post screening * Patients with symptoms and signs of clinically unacceptable deterioration of primary disease at time of screening * Previous treatment with irinotecan-based, nab-paclitaxel-based or gemcitabine-based resulting in disease progression

Study Objectives This is a Phase 1, open-label, nonrandomized study to determine the PK profiles of belinostat in patients with relapsed/refractory solid tumors or hematological malignancies who have heterozygous and homozygous UGT1A1\*28 genotypes and wild-type UGT1A1 gene. Enrolled patients will be assigned to 1 of 3 cohorts (A, B, or C) based on their UGT1A1 genotype Conditions: Solid Tumors, Hematological Malignancies Intervention / Treatment: DRUG: Belinostat IV Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patient is diagnosed with advanced solid tumors or advanced hematological malignancy that is relapsed/refractory, for which no standard salvage therapy exists. * Patient must have received at least 1 prior systemic therapy for the current malignancy and has recovered from any toxicity of the prior therapy at screening. * Patient has adequate hematological and hepatic functions. Exclusion Criteria: * Patient is taking UGT1A1 inhibitors (eg, atazanavir, gemfibrozil, indinavir, ketoconazole, sorafenib) at screening. * Patient has HBV or HCV * Patient has a known HIV positive diagnosis. * Patient has congestive heart failure Class III/IV * Patient has had previous exposure to belinostat.

Study Objectives The objectives of this study are to assess the safety and efficacy of single agent Tagrisso (Osimertinib, hereinafter "the study drug") in a real world setting in adult patients with advanced or metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), Who Have Progressed on or after EGFR tyrosine kinase receptor (TKI) therapy. Conditions: Non-Small Cell Lung Cancer Location: Korea, Republic of Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: * 1. Eligible for, or on active study drug treatment according to the approved label; patients with locally advanced or metastatic, EGFR T790M mutation-positive NSCLC, who have progressed on or after EGFR tyrosine kinase receptor (TKI) therapy * 2. Provision of signed and dated written informed consent by the patient or legally acceptable representative Exclusion Criteria: * 1. History of hypersensitivity to excipients of the study drug or to drugs with a similar chemical structure or class to the study drug * 2. Pregnancy and/or breast feeding * 3. Current participation in any interventional trial

Study Objectives The purpose of this research study is to evaluate the safety and effectiveness of patients with Polycythemia Vera treated with Gleevec. Conditions: Polycythemia Vera Intervention / Treatment: DRUG: Gleevec 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 have diagnosis of Polycythemia Vera (PV). Patients may have newly diagnosed PV. * Patients may have previously interferon-alfa treated PV with documented resistance, refractoriness or intolerance to interferon-alfa. * Patients may have PV with inadequate control on hydroxyurea. * Performance status of 0, 1, or 2 * Adequate end organ function, defined as the following: 1. total bilirubin <1.5 x upper limit of the normal range (ULN) 2. SGOT (AST) and SGPT (ALT) < 2.5 x ULN 3. creatinine < 1.5 x ULN 4. ANC > 1.5 x 109/L * Written voluntary informed consent. Exclusion Criteria: * Female patients who are pregnant or breast-feeding. * Patients receiving busulfan within 6 weeks of Study Day 1. * Patients receiving interferon-alpha within 4 weeks of Study Day 1. * Patients receiving hydroxyurea within 2 weeks of Study Day 1. * Patients with Grade III or IV cardiac problems as defined by the New York Heart Association Criteria. * Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable. * Patients previously treated with Gleevec. * Serum erythropoietin level > or = 25 units/microliter * Abnormal O2 saturation (by pulse oximetry) or arterial pO2 (by arterial blood gas).

Study Objectives The rationale for this study is to investigate the benefits of epidural analgesia in pancreatic resections in a prospective, single blind, randomized control trial. This study will evaluate both short and long-term outcomes related to epidural analgesia, providing a longitudinal and comprehensive perspective to the advantages and disadvantages of this technique. The investigators hypothesize that the use of epidural analgesia reduces a patient's consumption of morphine or morphine-equivalent in the post-operative period following pancreatic resections. Conditions: Cancer of Pancreas, Cancer of the Pancreas, Pancreas Cancer, Pancreas Neoplasms, Pancreatic Cancer Intervention / Treatment: DRUG: Bupivacaine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * Undergoing pancreatic resection. * Age >=18 years old. * Able to understand and sign an Institutional Review Board (IRB)-approved informed consent form. Exclusion Criteria: * Indication for operative intervention being chronic pancreatitis. * Currently on warfarin with an INR>=1.4 or clopidogrel that cannot be discontinued 7 days prior to surgery; * Most recent INR prior to surgery >1.4 * Most recent platelet count prior to surgery <70,000/mcl * Chronic opioid use as defined by use of more than 20mg oxycodone, or equivalent, daily. * History of pre-existing neuropathic pain conditions. * Not giving consent for study participation. * Known medical history of significant psychiatric or cognitive impairment * History of HIV, Hepatitis B, and/or Hepatitis C

Study Objectives This pilot clinical trial studies how well buparlisib works in treating patients with non-Hodgkin lymphoma that has returned after a period of improvement or has not responded to previous treatment. Buparlisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Conditions: Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Refractory Mantle Cell Lymphoma, Transformed Recurrent Non-Hodgkin Lymphoma Intervention / Treatment: DRUG: Buparlisib, OTHER: Laboratory Biomarker Analysis, OTHER: Questionnaire Administration 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: * Biopsy-proven relapsed, refractory or residual aggressive B-cell non-Hodgkin lymphoma; NOTE: re-biopsy is necessary unless the patient has had a previous biopsy < 168 days prior to registration on this protocol and there has been no intervening treatment; eligible tumor types are diffuse large B-cell non-Hodgkin lymphoma (NHL), mantle cell lymphoma, transformed NHL, and follicular grade III * Not a candidate or has declined standard salvage therapy for their disease * Measurable disease as defined by at least ONE of the following: * Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) or the CT portion of the positron emission tomography (PET)/CT: must have at least one lesion that has a single diameter of >= 2 cm or tumor cells in the blood >= 5 x 10^9/L * Skin lesions can be used if the area is >= 2 cm in at least one diameter and photographed with a ruler * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 * Absolute neutrophil count (ANC) >= 1000/uL * Hemoglobin (Hgb) >= 9 g/dl * Platelets (PLT) >= 100,000/uL * Serum bilirubin within normal range (or =< 1.5 x upper limit of normal [ULN] if liver metastases are present; or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert syndrome) * Aspartate aminotransferase (AST) within normal limits or =< 3 x ULN if due to lymphoma * Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min * Magnesium >= lower limit of normal (LLN) * Potassium >= LLN * Serum amylase =< ULN * Serum lipase =< ULN * Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L) * Serum calcium =< 10.9 mg/dL * Negative pregnancy test done =< 72 hours prior to starting drug, for women of childbearing potential only * Provide informed written consent * Willing to return to Mayo Clinic Rochester for follow-up * Willing to provide blood samples for correlative research purposes * Willingness to take BKM120 orally Exclusion Criteria: * Any of the following: * Pregnant women * Nursing women * Women of childbearing potential who are unwilling to employ highly effective contraception during dosing with BKM120 and for 4 weeks after the final dose of treatment; NOTE: women of childbearing potential are defined as all women physiologically capable of becoming pregnant * Men of childbearing potential who are unwilling to employ highly effective contraception during dosing with BKM120 and for 16 weeks after the final dose of treatment and should not a father a child during this time; NOTE: men of childbearing potential are defined as all males physiologically capable of conceiving offspring * NOTE: the highly effective contraception is defined as either: * True abstinence: when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception * Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment * Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); for female subjects on the study, the vasectomized male partner should be the sole partner for that patient * Use of a combination of any two of the following (a+b): 1. Placement of an intrauterine device (IUD) or intrauterine system (IUS) 2. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository * Oral contraception, injected or implanted hormonal methods are not allowed * Uncontrolled infection * Average baseline of >= 4 stools per day * Therapy with myelosuppressive chemotherapy or biologic therapy < 21 days prior to registration unless the patient has recovered from the nadir of the previous treatment to a level that meets the inclusion eligibility criteria of this protocol * Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) =< 5 effective half-lives prior to registration or who have not recovered from side effects of such therapy * Received wide field radiotherapy =< 28 days or limited field radiation for palliation =< 14 days prior to registration or who have not recovered from side effects of such therapy * Receiving corticosteroids > 10 mg of prednisone per day (or equivalent); NOTE: patients may be receiving stable doses of corticosteroids with a maximum dose of 10 mg of prednisone per day if they are being given for disorders other than lymphoma such as rheumatoid arthritis, polymyalgia rheumatica or adrenal insufficiency, or asthma * Persistent toxicities >= grade 2 from prior chemotherapy or biological therapy regardless of interval since last treatment * Active cardiac disease including any of the following: * Left ventricular ejection fraction (LVEF) < 45% as determined by multi gated acquisition (MUGA) scan or echocardiogram (ECHO) * Fridericia's corrected QT interval (QTcF) > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula) * Unstable angina pectoris; patients with unstable angina should have angina controlled before entering the study * Ventricular arrhythmias except for benign premature ventricular contractions * Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication * Conduction abnormality requiring a pacemaker * Symptomatic pericarditis * Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function * History of documented congestive heart failure (New York Heart Association functional classification III-IV) * Documented cardiomyopathy * Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation) * Known positivity for human immunodeficiency virus (HIV); note: baseline testing for HIV is not required * Active hepatitis B or C with uncontrolled disease; note: a detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients; hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) ribonucleic acid (RNA) polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior hepatitis B virus (HBV) infection * Other active malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment * Inability to swallow or impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) that would preclude use of oral medications * Any severe and/or uncontrolled medical conditions such as diabetes, poor lung function, or other conditions that, in the treating physician's opinion, could adversely impact their ability to participate in the study * Patients who have received prior treatment with a P13K inhibitor; patients with prior mammalian target of rapamycin (mTOR) inhibitor therapy are eligible * Using medications that have a strong risk of prolonging the QT interval or inducing torsades de pointes * Major surgery =< 14 days prior to registration or have not recovered from side effects of such therapy * Currently being treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5), (please note that co-treatment with weak inhibitors of cytochrome P450, family 3, subfamily A [CYP3A] is allowed) * Receiving certain fruits or herbal preparations/medications including, but are not limited to: St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, ginseng; fruits include the CYP3A inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits; NOTE: patients should stop using these fruits and herbal medications 7 days prior to first dose of study drug * Primary central nervous system (CNS) lymphoma or active metastases to the CNS; NOTE: active is defined as requiring therapy such as surgery, radiation, or chemotherapy =< 28 days of study registration or ongoing corticosteroid therapy for CNS disease * The following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire: * 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) * >= Common Terminology Criteria of Adverse Events (CTCAE) grade 3 anxiety * Meets the cut-off score of >= 12 in the Patient Health Questionnaire (PHQ)-9 or a cut-off of >= 15 in the Generalized 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) * Treated with any hematopoietic colony-stimulating growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF]) =< 2 weeks prior to study registration; NOTE: erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to study registration, may be continued

Study Objectives This study is designed to examine blood levels of ASTX727, a fixed-dose combination tablet containing the combination of cedazuridine (100 mg) and decitabine (35 mg), when given under fed versus fasted conditions to participants with myelodysplastic syndromes (MDS), including refractory anemia with excess blasts in transformation or chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML). This study will also assess the safety of ASTX727. Conditions: Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, Acute Myeloid Leukemia Intervention / Treatment: DRUG: ASTX727 + Day 2 Food, DRUG: ASTX727 + Day 4 Food Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: BASIC_SCIENCE Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * Able to understand and comply with the study procedures, including the ability to completely consume the breakfast meal in 20 minutes, understand the risks involved in the study, and provide written informed consent before the first study-specific procedure. * Men or women >=18 years with either: 1. MDS, including all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, CMML), and subjects with MDS IPSS int-1, -2, or high-risk MDS. 2. AML, as diagnosed according to the 2016 WHO guidelines on acute leukemia, of any subtype except M3 (Acute Promyelocytic Leukemia), who are not candidates for intensive chemotherapy * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. * Adequate organ function defined as follows: 1. Hepatic: Total or direct bilirubin <=2 × upper limit of normal (ULN); aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) <=5 × ULN. 2. Renal: serum creatinine <=1.5 × ULN or if serum creatinine is elevated; calculated creatinine clearance or glomerular filtration rate >=50 mL/min. * Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. * Subjects and their partners with reproductive potential must agree to use 2 highly effective contraceptive measures during the study and must agree not to become pregnant or father a child for 3 months after the last dose of study treatment. Exclusion Criteria: * Known or suspected hypersensitivity to decitabine, azacitidine, or cedazuridine. * Treated with any investigational drug or therapy within 2 weeks of study treatment, or 5 half-lives, whichever is longer, before the protocol-defined first dose of study treatment, or ongoing clinically significant adverse events (AEs) from previous treatment with investigational drug or therapy. * Poor medical risk because of other conditions such as uncontrolled systemic diseases or active uncontrolled infections. * Life-threatening illness, medical condition or organ system dysfunction, or other reasons including laboratory abnormalities, which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of decitabine + cedazuridine or compromise the integrity of the study outcomes. * Prior gastric surgery for ulcer disease, weight loss, etc., that would impair normal motility or absorption. * Second malignancy currently requiring active chemotherapy. To clarify, patients with breast or prostate cancer stable on or responding to endocrine therapy, are eligible. * Known history of human immunodeficiency virus or if known seropositive for hepatitis C virus or hepatitis B virus. * Active uncontrolled gastric or duodenal ulcer. * Subjects with Acute Promyelocytic Leukemia.

Study Objectives Patients with localised prostate cancer can be treated by radical prostatectomy (prostate gland removal surgery) or radiotherapy. Around 15% of men with prostate cancer are diagnosed with high risk disease meaning they are more likely to suffer treatment failure, disease progression and mortality. To date little progress has been made towards identifying effective treatment strategies that might delay or prevent disease recurrence in this patient population. Better identification of patients at high risk of relapse and improvements in therapy are therefore research priorities. A protein named Mammalian Target of Rapamycin (mTOR) is known to play an important role in the development of prostate cancer. mTOR forms two protein complexes (mTORC1 and mTORC2) and sends signals helping cancer cells to grow while controlling their energy use. Blocking the function of mTOR, with an inhibitor such as AZD2014, might shut down the supply of energy supply to tumour cells leading to reduced cell growth and potentially slowing the progression of the disease. The purpose of this study is to investigate the molecular pharmacology of AZD2014 treatment given to patients with prostate cancer prior to radical prostatectomy. The feasibility, safety and tolerability of a short course of AZD2014 will also be assessed. Conditions: Prostate Cancer Intervention / Treatment: DRUG: AZD2014 Location: United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Men aged 18 years old or older * ECOG performance status of 0 or 1 * Clinical diagnosis of Intermediate (one or more of stage T2, or PSA >10ng/mL, or Gleason score of at least 7) or High Risk Prostate Cancer (one or more of stage T2c, or PSA >20ng/mL, or Gleason score of at least 8) * Patient suitable for radical prostatectomy, following discussion at specialist MDT and subsequent review by surgical team * Willing to use barrier contraceptive method, e.g. condom & spermicide * Adequate bone marrow reserve or organ function (as specified in the study protocol) * Normal chest radiograph and oxygen saturations, OR normal CT thorax Exclusion Criteria: * Contraindication to AZD2014 (as specified in the study protocol) * Patients who have experienced any of the following procedures in the past 12 months: coronary artery bypass graft; angioplasty; vascular stent; myocardial infarction; angina pectoris; congestive heart failure (New York Heart Association grade of 2 or above); ventricular arrhythmias requiring continuous therapy; supraventricular arrhythmias including atrial fibrillation, which are uncontrolled; haemorrhagic or thrombotic stroke including transient ischaemic attacks or any other CNS bleeding. * Previous chemotherapy, biological therapy, radiation therapy, androgens, thalidomide, immunotherapy, other anticancer agents and/or investigational agents within 28 days of starting study treatment. * Major surgery within 4 weeks prior to study entry (excluding placement of vascular access), or minor surgery within 2 weeks of entry into the study * Potent or moderate inhibitors and inducers of CYP2C8 if taken within the stated wash-out period: Gemfibrozil, trimethoprim, glitazones, montelukast, deferasirox and quercetin (1-week minimum wash out period) * Any haematopoietic growth factors, e.g. G-CSF, GM-CSF, within 4 weeks prior to receiving study drug * As judged by the Investigator, any evidence of severe or uncontrolled systemic disease (as specified in the study protocol) * Abnormal ECHO or MUGA at baseline * Mean resting QTc of 470msec or above (as per local reading) * Concomitant medications known to prolong QT interval, or with factors that increase the risk of QTc prolongation, or risk of arrythmic events (examples specified in study protocol). History of Torsades de Pointes. * Patients with Diabetes Type I or uncontrolled Type II as judged by the investigator * Judgement by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements. * Unable to provide informed consent

Study Objectives This is a study of the safety and efficacy of adavosertib in combination with paclitaxel plus carboplatin in the treatment of ovarian, fallopian tube, and primary peritoneal tumors with the P53 mutation. In Part 1, a small group of participants will receive adavosertib along with paclitaxel plus carboplatin to establish the tolerability of adavosertib with this combination. In Part 2, participants will be randomly assigned to receive either adavosertib plus paclitaxel and carboplatin OR placebo plus paclitaxel and carboplatin to assess efficacy of adavosertib compared to placebo. The primary hypothesis of the study (Part 2) is that administration of adavosertib in combination with paclitaxel plus carboplatin in participants with platinum sensitive p53 mutant ovarian cancer will result in improvement in progression free survival (PFS) per enhanced Response Evaluation Criteria In Solid Tumors version 1.1 (enhanced RECIST 1.1) compared to participants treated with paclitaxel plus carboplatin alone. Conditions: Ovarian Cancer Intervention / Treatment: DRUG: adavosertib, DRUG: Placebo, DRUG: paclitaxel, DRUG: carboplatin Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Histologically confirmed non-low grade, non-borderline (low malignant potential) ovarian, fallopian tube, or primary peritoneal cancer which has progressed after paclitaxel / platinum-based therapy. * Platinum-sensitive disease. Radiological progression must have occurred 6 months or more after the completion of the most recent platinum-based treatment. * Measurable disease. * Available tumor sample(s). * Performance status of <=1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. * Adequate organ function. Exclusion Criteria: * Pregnancy or the intention to become pregnant during the course of the study. * Participation in a study with an investigational compound or device within 28 days of receiving first dose of study medication. * Active central nervous system (CNS) metastases and/or carcinomatous meningitis. * Primary CNS tumor. * Known hypersensitivity or contraindications to the components of potential study therapy (paclitaxel, carboplatin, adavosertib) or its analogs (i.e., cremophor, mannitol, etc.). * Participant requires the use of medications or products that are metabolized by, or inhibit, or induce Cytochrome P450 3A (CYP3A4). * Ongoing peripheral neuropathies >=Grade 2 and related to previous treatment. * Known psychiatric or substance abuse disorders. * Regular use (including "recreational use") of any illicit drugs or recent history (within the last year) of drug or alcohol abuse. * HIV positive. * Active Hepatitis B or C. * Symptomatic ascites or pleural effusion. * Clinical history suggestive of Li Fraumeni Syndrome.

Study Objectives The purpose of this dose-escalation study is to assess the safety and tolerability of treatment with Chiauranib administered orally over a range of doses in patients with advanced solid tumors. Conditions: Solid Tumors Intervention / Treatment: DRUG: Chiauranib Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histological or cytological confirmation of advanced solid tumor, including non-small cell lung cancer, colorectal cancer, ovarian cancer, renal cell carcinoma, gastrointestinal stromal tumor, gastric cancer, et al; * Patients with advanced solid tumors refractory to standard therapy or for which no standard therapy exists; * Body mass index (BMI) is between 18 and 28; * Age: 18~65 years; * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1; * Laboratory criteria are as follows: 1. Complete blood count: hemoglobin (Hb) >=100g/L (no blood transfusion within 14 days); absolute neutrophil count (ANC) >=1.5×109/L ; platelets >=100×109/L 2. Biochemistry test: serum creatinine <=1.5×upper limit of normal (ULN); total bilirubin≦1.5×ULN; alanine aminotransferase / aspartate aminotransferase≦1.5×ULN; fasting triglyceride (TG) <= 3.0 mmol/L; total cholesterol <= 7.75 mmol/L 3. Coagulation test: International Normalized Ratio (INR) < 1.5 * Women of child-bearing potential should be non-lactating patients, and must agree to use effective contraceptive methods prior to study entry, during study participation, and up to 6 months following completion of therapy. A serum or urine pregnancy test within 7 days before enrollment must be negative; Men must agree to use effective contraceptive methods during study participation and up to 6 months following completion of therapy; * Willingness to sign a written informed consent document Exclusion Criteria: * Life expectation < 3 months; * Subjects received anti-cancer therapy (including chemotherapy, radiotherapy, targeted therapy and endocrine therapy, et al) within 4 weeks prior to study entry; Subjects received nitrosoureas or mitomycin chemotherapy within 6 weeks prior to study entry; * Have uncontrolled or significant cardiovascular disease, including: 1. Myocardial infarction (< the last 12 months) 2. Uncontrolled angina (< the last 6 months) 3. Congestive heart failure (< the last 6 months), or Left Ventricular Ejection Fraction (LVEF) < 50% prior to study entry 4. History of any significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or TdP) 5. History of significant QT interval prolongation, or Corrected QT Interval (QTc) > 450 ms prior to study entry 6. History of cerebrovascular accident 7. Symptomatic coronary heart disease requiring treatment with agents 8. Uncontrolled hypertension (> 140/90 mmHg) by single agent; * Have active bleeding , current thrombotic disease, or patients with bleeding potential receiving anticoagulation therapy; * History of deep vein thrombosis or pulmonary embolism; * Have unsolved toxicities (> grade 1) from prior anti-cancer therapy; * Have clinical significant gastrointestinal abnormality, e.g., unable to swallow, chronic diarrhea, ileus, that would impair the ingestion,transportation or absorption of oral agents, or patients undergone gastrectomy; * Have symptomatic brain metastasis; * History of organ transplantation; * Proteinuria positive; * Congenital or acquired immunodeficiency, active infections; * Any mental or cognitive disorder, that would impair the ability to understand the informed consent document or the operation and compliance of study; * Any other condition which is inappropriate for the study in the opinion of the investigators.

Study Objectives Major surgery can result in blood loss that can require a blood transfusion during and/or after surgery. Tranexamic acid is a medication that was first introduced in the 1960s as a treatment for heavy menstrual bleeding. Over the past 20 years it has been used and studied in patients undergoing open-heart surgery, liver transplantation, and urologic surgery. We believe tranexamic acid may possibly decrease bleeding related to major surgery, resulting in reduced blood loss, lower blood transfusion rates, and possibly decreased hospital costs related to your surgical hospital stay. In this study, you will receive either the drug tranexamic acid or a placebo. The placebo looks like the tranexamic acid, but does not have any active ingredient in it. The treatment you get will be chosen by chance, like flipping a coin. You will have equal chance of being given the tranexamic acid or the placebo. In this study, both the tranexamic acid and the placebo are considered research. Conditions: Tranexamic Acid, Cancer, Major Surgery Intervention / Treatment: DRUG: Tranexamic Acid, OTHER: Placebo Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria * Subjects undergoing major oncologic surgery for standard of care purposes (to include, but not limited to: liver resections, radical cholecystectomy, pancreaticoduodenectomy (Whipple procedure), esophagectomy, gastrectomy, colectomy, debulking with hyperthermic intraperitoneal chemotherapy, prostatectomies, nephrectomies and partial nephrectomies) * Male or female > 18 years of age * Subject agrees to participate in this study and provides informed consent Exclusion Criteria * Subjects with a history of hypercoagulopathy, deep vein thrombosis or pulmonary embolism * Subjects that are on therapeutic anticoagulation or therapeutic antiplatelet medications at the time of surgery other than Aspirin * Subjects with a history of TIA or stroke * Subjects with a history of atrial fibrillation * Subjects with a known thrombus * Baseline creatinine level greater than 2.83 mg/dL * Subjects with known hypersensitivity to tranexamic acid * Adults unable to provide informed consent * Children * Pregnant women * Prisoners * Non-English speaking subjects * Any other medical condition including mental illness or substance abuse deemed by the investigator to be likely to interfere with a subject's ability to provide informed consent, cooperate and take part in this research study

Study Objectives A Phase 2 study to evaluate safety and efficacy of sildenafil taken orally to improve or resolve lymphatic malformations in children. Subjects may receive either placebo or treatment in an oral dosage with an open label extension for subjects who received placebo. The study treatment assignment will be randomized in a double blind fashion. MRI examination will evaluate change in lesion volume due to treatment. Other safety and efficacy measures will be taken through the 32-week study duration. Funding Source - FDA OOPD Conditions: Lymphatic Malformations, Lymphatic Diseases Intervention / Treatment: DRUG: Sildenafil 20 mg tablets, OTHER: Placebo tablets (resembling Revatio) Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: Subjects must: * Be legally authorized representative of subjects willing and able to give consent. Assent obtained for subjects 7 - 10 years old. * Be between the ages of 6 months - 10 years of age at the time of entry into the study. * Be at the minimum weight of 8 kg at the time of enrollment. * Be required to have the clinical diagnosis of lymphatic malformation that appears to be over 3 cm in greatest diameter in order to be evaluated for entry. A review of a previous MRI examination may help confirm the entry criteria on subjects selected to come to Stanford for the MRI screening. * Have the lymphatic malformation cause enough disability for the subject that requires them to consider systemic therapy. * For female subjects: must not be pregnant or breast-feeding. * Have a parent or legally authorized representative willing and able to ensure subject is present for all required study visits. * Have a required MRI examination to confirm that the lymphatic malformation is present and is greater than 3 cm in diameter in order for the subjects to receive medication, which happens during the initial screening evaluation portion of the trial. * Have no contraindications for the use of sildenafil. * Have a normal eye examination. * Have normal liver and kidney function. * Have no contraindication to MRI examinations such as metal implants, etc. * Not be a smoker. Exclusion Criteria: A Subject with any of the following criteria is not eligible for inclusion in this study: * Medically unstable health status that may interfere with his/her ability to complete the study. * Has one or more of the following medical conditions: Hepatic impairment, severe renal impairment, lymphedema conditions such as Milroy disease, Meige lymphedema, Hennekam syndrome, Njolstad syndrome, Aagenaes syndrome, and Fabry disease, hypotension or at risk for hypotension, seizures or history of seizures, any significant cardiovascular risk factors and any condition which requires participants to use nitric oxide donors or nitrates in any form, underlying anatomic or vascular risk factor for developing non-arteritic anterior ischemic optic neuropathy (NAION) including low ocular cup to disc ratio, diabetes, hypertension, coronary artery disease, or hyperlipidemia Participants with Down syndrome, Turner syndrome and Noonan syndrome will be considered on a case-by-case basis. * Has received at least one of the following medications contraindicated in association with sildenafil within 15 days of inclusion: * Organic nitrates in any form, either regularly or intermittently -- Consistent with its known effects on the nitric oxide/cGMP pathway, sildenafil was shown to potentiate the hypotensive effects of nitrates. * Ritonavir and other Potent CYP3A Inhibitors --- Concomitant use of REVATIO with ritonavir and other potent CYP3A inhibitors is not recommended. * Alpha-blockers --- co-administering alpha-blockers with REVATIO because of additive blood pressure-lowering effects * Amlodipine * Cimetidine * Requires concomitant use of potent cytochrome P450 3A4 inhibitors (such as ketoconazole, itraconazole, erythromycin, saquinavir), or concomitant use of ritonavir. Also excluded are concomitant use of organic nitrates, alpha-blockers, amlodipine, or cimetidine. * Cannot confirm that the lesion is a lymphatic malformation or the lymphatic malformation is less than 3 cm in its greatest diameter during the MRI screening. * Has had extensive prior surgery or sclerotherapy to treat LM such that scarring may interfere with evaluation and treatment effect of sildenafil. * Have had recurrent infection and significant scarring of the lesion secondary to infection to such an extent that the that scarring may interfere with evaluation and treatment effect of sildenafil * Known to have an allergy to sildenafil. * Has ulcerated or currently infected LMs. * Has diagnosis of the soft tissue tumor as LM not clinically certain. * Participating in another clinical study which may interfere. * Has a history of priapism or is diagnosed with sickle cell anemia or any other disorder which may predispose to priapism.

Study Objectives Breast cancer is the most common cancer and the second cause of cancer mortality in women. There are approximately 200,000 new cases of breast cancer a year. Classically, breast cancers are divided into two groups, invasive and non-invasive. A mainstay of the treatment of both of these types is surgical resection not only for therapeutic purposes but also for diagnostic purposes. Breast conserving therapy includes surgical lumpectomy and post-operative radiation. However, despite best surgical practices, when patients undergo BCT anywhere from 20 - 40% of these patients have margins positive for cancer. This leads to increased rates of reoperation which are quoted to be as high as 30% and increased local recurrences. There is an over expression of folate receptors located on the surface of many human carcinoma nodules.Specifically for breast cancer up to 33% of all breast cancers over express the folate receptor. Folate-fluorescein isothiocyanate, or folate-FITC, also identified as EC-17, targets folate receptors over expressed in certain cancers such as breast cancer, and could help in better identifying the margins of the cancer thereby achieving negative margins. Conditions: Resectable Breast Cancer Intervention / Treatment: DRUG: EC17 Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: DIAGNOSTIC Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Adult patients 18 years of age and older * Patients presenting with breast cancer presumed to be resectable by lumpectomy and/or mastectomy on pre-operative assessment * Good operative candidate * Subject capable of giving informed consent and participating in the process of consent. Exclusion Criteria: * Pregnant women as determined by urinary or serum beta hCG within 72 hours of surgery * Patients with a history of anaphylactic reactions to Folate-FITC or insects * At-risk patient populations 1. "People who would be easily lost to follow up (ex: People who are homeless or alcohol dependent) 2. Patients unable to participate in the consent process (children and neonates).

Study Objectives This study will evaluate the pharmacodynamics, pharmacokinetics, safety, and biologic activity of giredestrant in participants with Stage I-III operable estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, untreated breast cancer. Conditions: Breast Cancer Intervention / Treatment: DRUG: Giredestrant, PROCEDURE: Surgery Location: Spain, United Kingdom, United States, Belgium, Australia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: BASIC_SCIENCE Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Ability to comply with the study protocol, in the investigator's judgment * Histologically confirmed invasive breast carcinoma, with all of the following characteristics: Primary tumor greater than or equal to (>=)1.5 centimeters (cm) in largest diameter by ultrasound; Stage I-III operable breast cancer; Documentation confirming the absence of distant metastasis (M0) as determined by institutional practice. * ER-positive tumor and HER2-negative breast cancer as per local laboratory testing * Postmenopausal status * Breast cancer eligible for primary surgery * Submission of a representative tumor tissue specimen * Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to (<=)1 * Adequate organ function Exclusion Criteria: * Diagnosis of inflammatory breast cancer * Diagnosis of bilateral breast cancer * Concurrent use of hormone replacement therapies * Previous systemic or local treatment for the primary breast cancer currently under investigation * Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study entry * Current treatment with any systemic anti-cancer therapies * Major surgery within 4 weeks prior to enrollment * Radiation therapy within 2 weeks prior to enrollment * Diagnosis of any secondary malignancy within 3 years prior to enrollment, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer * Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or upper gastrointestinal surgery including gastric resection * Known HIV infection * Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis, current alcohol abuse, or cirrhosis * Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study * History of allergy to giredestrant or any of its excipients * Any condition requiring anti-coagulants, such as warfarin, heparin, or thrombolytic drugs * History of documented hemorrhagic diathesis or coagulopathy * History or presence of symptomatic bradycardia or sick sinus syndrome * Baseline heart rate <=55 beats per minute (bpm) prior to enrollment * History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third-degree heart block, or evidence of prior myocardial infarction * QT interval corrected through use of Fridericia's formula (QTcF) >470 milliseconds demonstrated by at least two ECGs >30 minutes apart * History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease, coronary heart disease, clinically significant electrolyte abnormalities, or family history of sudden unexplained death or long QT syndrome * Current treatment with medications that are well known to prolong the QT interval * History or presence of uncontrolled hypothyroidism * Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications

Study Objectives The study design is a prospective randomized, double-blind, controlled trial of patients who are due to have elective laparoscopic colorectal surgery in Ramathibodhi Hospital. The primary objective is to measure pain scores (Visual Analog Scale) in the postoperative period. The secondary objective is to compare the VAS scores between the two types of technique used for specimen retrieval incision.After approval by the ethics committee, patients scheduled for elective laparoscopic colorectal surgery under general anesthesia who are eligible for inclusion criteria were recruited for this study after informed consent by surgical residents or surgical staff at the Outpatient Department (OPD). Patients who meet the exclusion criteria will be excluded. Conditions: Laparoscopic Colorectal Surgery, Colorectal Cancer Intervention / Treatment: PROCEDURE: 0.5% Levobupivacaine, OTHER: Control Location: Thailand Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: OTHER Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * Patients scheduled for elective laparoscopic colorectal surgery under general anesthesia. * ASA (American Society of Anesthesiologists) classification 1 and 2 * Laparoscopic colorectal surgery including Laparoscopic segmental colonic resection, laparoscopic anterior resection and laparoscopic low anterior resection Exclusion Criteria: * Conversion to open surgery. * Patients receive epidural anesthesia. * Patients have history allergy to aminoamides.

Study Objectives To study the effect of combined diazoxide-metformin therapy on body weight in youth with hypothalamic obesity following treatment for craniopharyngioma. A secondary objective is to evaluate changes in insulin resistance (IR), beta-cell function, features of the metabolic syndrome, muscle metabolism and intramyocellular lipid. Hypothesis: Treatment with diazoxide and metformin will result in weight loss or slowed weight gain and improved metabolic profile, compared to pretreatment levels. Conditions: Hypothalamic Obesity Intervention / Treatment: DRUG: Diazoxide, DRUG: Metformin Location: Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Craniopharyngioma at least one year following surgery * Evidence of at least one other endocrinopathy of hypothalamic origin * Stable hormone replacement therapy (with one or more of thyroxine hydrocortisone, DDAVP, sex steroids and GH) * Obesity, defined as weight >120% Ideal Body Weight (IBW) or BMI > 27 kg/m2, with normal weight for height before tumour diagnosis and weight gain >2SD above mean for age for 1 year following tumour treatment (41). * Age 9 -22 years * Minimum of 6 months of standard diet and exercise intervention (run-in period). This was chosen to allow a period of prospective measurements to establish individual baseline slope of change in BMI SDS prior to initiation of active treatment with diazoxide and metformin. Exclusion Criteria: * Contraindications for Metformin or Diazoxide use (history or evidence of cardiac, renal, or progressive hepatic disease , diabetes or hypoxic conditions) * Pharmacologic doses of glucocorticoids or use of other medications known to affect glucose metabolism (e.g. beta-blockers, oral hypoglycemics) * Growth hormone (GH) initiation in the preceding 6 months or planned initiation in the next 6 months (to rule out potential confounding effect of GH on weight / body composition and glucose metabolism). * Use of other weight loss medications * Inability of the family and/or patient to comply with study protocol * Non English speaking

Study Objectives This partially randomized phase I/II trial studies the side effects and the best dose of anti-endoglin monoclonal antibody TRC105 when given together with bevacizumab and to see how well they work in treating patients with glioblastoma multiforme that has come back. Monoclonal antibodies, such as anti-endoglin monoclonal antibody TRC105 and bevacizumab, may find tumor cells and help kill them. Giving anti-endoglin monoclonal antibody TRC105 together with bevacizumab may be an effective treatment for glioblastoma multiforme. Conditions: Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma, Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Adult Mixed Glioma, Recurrent Adult Brain Neoplasm Intervention / Treatment: BIOLOGICAL: Anti-Endoglin Chimeric Monoclonal Antibody TRC105, BIOLOGICAL: Bevacizumab, OTHER: Laboratory Biomarker Analysis, OTHER: Pharmacological Study, OTHER: Quality-of-Life Assessment Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histological confirmation of grade 3 or 4 glioma, including astrocytoma, oligodendroglioma, and mixed gliomas, as determined by pre-registration central pathology review (Phase I) * Histological confirmation of glioblastoma multiforme (grade 4 astrocytoma) as determined by pre-registration central pathology review; note: gliosarcomas and other grade 4 astrocytoma variants (e.g., giant cell) are eligible; glioblastoma (GBM) with oligodendroglial features are NOT PERMITTED in this study if they are 1p19q co-deleted; sites submitting GBM with oligodendroglial features will be asked to provide results of 1p/19q co-deletion status (Phase II) * Evidence of tumor progression by MRI or computed tomography (CT) scan following radiation therapy or following the most recent anti-tumor therapy; note: patients who have had surgical treatment at recurrence are eligible if they had a resection with measurable or non-measurable residual disease on postoperative imaging or if there is imaging evidence of disease progression as compared to the first postoperative scan * Measurable or evaluable disease by gadolinium MRI or contrast CT scan; note: patients who have had a gross total resection (GTR) are eligible on the basis of evaluable disease * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 * Absolute neutrophil count (ANC) >= 1,500/mm^3 * Platelet count >= 100,000/mm^3 * White blood cells (WBC) >= 3,000/mL * Hemoglobin >= 10.0 g/dL; note: this level may be reached by transfusion * Total bilirubin =< institutional upper limit of normal (ULN) * Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2 x ULN * Creatinine =< ULN * Life expectancy >= 12 weeks * Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only * Urine protein creatinine (UPC) ratio < 1; note: urine protein must be screened by urine analysis for UPC ratio; for UPC ratio >= 1.0, 24-hour urine protein must be obtained and the level should be < 1,000 mg for registration * Fixed or decreasing dose of corticosteroids (or no corticosteroids) >= 7 days prior to registration * Calculated glomerular filtration rate (GFR) must be >= 60 ml/min; GFR will be calculated as needed per institutional guidelines * Any number of prior chemotherapy regimens for recurrent disease (Phase I); =< 1 chemotherapy or other non-antiangiogenic regimen for recurrent disease (Phase II) * Last dose of bevacizumab >= 2 weeks prior to registration (Phase I); note: for the phase II study only, prior exposure to bevacizumab is not allowed * Surgery >= 4 weeks prior to registration * Completion of radiation therapy >= 12 weeks prior to registration and prior chemotherapy >= 4 weeks prior to registration (>= 6 weeks from nitrosourea-containing regimens) * Small molecular cell cycle inhibitors >= 2 weeks from registration * Ability to provide informed written consent * Ability to complete questionnaire(s) by themselves or with assistance * Willing to return to enrolling institution for follow-up * Willing to discontinue use of medications that inhibit platelet function >= 10 days prior to registration; aspirin at doses greater than 325 mg/day must be discontinued >= 10 days prior to registration and avoided through the study; note: nonsteroidal anti-inflammatory drug (NSAID) medications are recommended in place of aspirin; if NSAIDs or aspirin are used, histamine (H)-2 blockers and proton pump inhibitor (PPI) medications are recommended * Willing to provide mandatory blood and tissue samples for correlative research purposes (Phase I and II) Exclusion Criteria: * Any of the following: * Pregnant women * Nursing women * Men or women of childbearing potential who are unwilling to employ adequate contraception throughout the duration of the study and for at least 6 months after treatment has ended * Prior hypersensitivity to bevacizumab or toxicity requiring discontinuation of bevacizumab (Phase I) * Any prior exposure to any VEGF or VEGF inhibitor including, but not limited to, bevacizumab, cediranib, vandetanib, sunitinib, pazopanib, aflibercept, or sorafenib (Phase II) * Prior hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies (Phase I and II) * Prior hypersensitivity to triptan derivatives (Phase I and II) * Other active malignancy =< 3 years prior to registration; exceptions: non-melanotic skin cancer or carcinoma-in-situ of the cervix; note: if there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer * Uncontrolled infection * Immunocompromised patients or patients known to be human immunodeficiency virus (HIV) positive and currently receiving combination antiretroviral therapy; patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial * Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the prescribed regimens * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements * History of hypertensive crisis or hypertensive encephalopathy * Clinically significant cardiovascular disease defined as follows: * Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] > 160 mm Hg and/or diastolic blood pressure [DBP] > 90 mm Hg despite antihypertensive therapy) * History of cerebrovascular accident (CVA) within 6 months * Myocardial infarction or unstable angina within 6 months * New York Heart Association classification II, III, or IV cardiovascular disease * Serious and inadequately controlled cardiac arrhythmia * Significant vascular disease (i.e., aortic aneurysm, history of aortic dissection) * Clinically significant peripheral vascular disease * Evidence or history of bleeding diathesis (greater than normal risk of bleeding, i.e., hereditary hemorrhagic telangiectasia type I or HHT-1) or coagulopathy in the absence of therapeutic anti-coagulation or any hemorrhage/bleeding event > grade 3 within 4 weeks prior to registration; note: patients with full-dose anticoagulants are eligible provided the patient has been on a stable dose for at least 2 weeks of low molecular weight heparin; therapeutic Coumadin and aspirin doses > 325 mg daily are not allowed * Receiving any other investigational agent that would be considered as a treatment for the primary neoplasm * Prior treatment with TRC105 * Serious or non-healing wound, active ulcer, or untreated bone fracture * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess =< 6 months prior to registration * History of invasive procedures defined as follows: * Major surgical procedure, open biopsy, or significant traumatic injury =< 28 days prior to registration * Anticipation of need for major surgical procedures during the study * Core biopsy =< 7 days prior to registration * History of significant vascular disease (i.e., aortic aneurysm requiring surgical repair, or recent peripheral arterial thrombosis) within 6 months prior to registration

Study Objectives This phase II trial is studying how well ABT-751 works in treating children with neuroblastoma that has relapsed or not responded to previous treatment. Drugs used in chemotherapy, such as ABT-751, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Conditions: Disseminated Neuroblastoma, Recurrent Neuroblastoma Intervention / Treatment: DRUG: ABT-751, PROCEDURE: quality-of-life assessment Location: United States, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed neuroblastoma meeting the following criteria: * Refractory or relapsed disease * No curative treatment option and no additional therapy proven to prolong survival with an acceptable quality of life is available * Evidence of disease progression (enlargement of existing measurable tumors or the appearance of new tumors) during prior treatment OR biopsy-proven viable neuroblastoma if stable disease but refractory to prior treatment * Previously irradiated soft tissue or bony lesion must meet >= 1 of the following criteria: * Viable neuroblastoma determined by biopsy >= 6 weeks after radiation therapy * Growth in the lesion determined by CT scan or MRI * Measurable or evaluable disease * Measurable disease is defined as >= 20 mm in >= 1 dimension by MRI, CT scan, or x-ray OR >= 10 mm in >= 1 dimension by spiral CT scan * Evaluable disease is defined as iodine I 123 metaiodobenzylguanidine (^123I MIBG)-positive lesion at >= 1 site * Must not have measurable disease by CT scan or MRI * No elevated urinary catecholamines and/or bone marrow evidence of tumor, without measurable or evaluable disease by imaging modalities (CT scan, MRI, or ^123I MIBG) * Karnofsky performance status (PS) 50-100% (> 16 years of age) OR Lansky PS 50-100% (<= 16 years of age) * Life expectancy >= 8 weeks * Hemoglobin >= 7.5 g/dL (transfusions allowed) * Absolute neutrophil count > 250/mm³ * Platelet count > 25,000/mm³ (without platelet transfusion support for >= 7 days) * Bilirubin <= 1.5 times upper limit of normal (ULN) * ALT < 5 times ULN * Creatinine normal for age and gender as follows: OR creatinine clearance or radioisotope glomerular filtration rate >= 60 mL/min * No greater than 0.4 mg/dL (<= 5 months) * No greater than 0.5 mg/dL (6 months-11 months) * No greater than 0.6 mg/dL (1 year-23 months) * No greater than 0.8 mg/dL (2 years-5 years) * No greater than 1.0 mg/dL (6 years-9 years) * No greater than 1.2 mg/dL (10 years-12 years) * No greater than 1.4 mg/dL (13 years and over [female]) * No greater than 1.5 mg/dL (13 years to 15 years [male]) * No greater than 1.7 mg/dL (16 years and over [male]) * Shortening fraction >= 27% by echocardiogram * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective double-barrier contraception during and for 90 days after completion of study treatment * Seizure disorder allowed if controlled and receiving anticonvulsants * Neurologic toxicity from prior therapy or tumor involvement <= grade 2 * No evidence of active graft-vs-host disease * No allergy to sulfa-containing medications * No known HIV positivity * No clinically significant unrelated systemic illness (e.g., serious infection) that would limit study compliance * Concurrent filgrastim (G-CSF) allowed if medically indicated * Recovered from all prior therapy * No prior ABT-751 * More than 2 weeks since prior myelosuppressive chemotherapy * More than 7 days since prior anticancer biologic agents (e.g., retinoids) * More than 4 weeks since prior palliative radiation therapy (small port) or therapeutic ^123I MIBG * More than 6 weeks since prior substantial radiation therapy (> 50% pelvis, craniospinal, or total-body radiation) * More than 4 months since prior allogeneic stem cell transplantation (SCT) (2 months for autologous SCT) and recovered * Infusion of autologous peripheral blood mononuclear cells without high-dose chemotherapy or preparative regimen is not considered SCT * More than 30 days since prior investigational drug therapy * More than 30 days since prior immunotherapy (monoclonal antibody therapy or vaccine therapy) * More than 1 week since prior growth factor treatment * No other concurrent anticancer agents, including chemotherapy, immunomodulating agents, or biologic therapy (retinoids) * No concurrent radiation therapy, including palliative radiation therapy * No concurrent treatment for graft-vs-host disease * No concurrent epoetin alfa, sargramostim (GM-CSF), or interleukin-11

Study Objectives Cabergoline prevents ovarian hyperstimulation syndrome in high risk patients by disrupting follicular fluid hormone microenvironmentally altering the follicular fluid levels of insulin like growth hormone -I (IGF-I), antimullerian hormone (AMH), inhibin B and hepatocyte growth factor (HGF) levels in women with PCOS and high risk of ovarian hyperstimulation syndrome (OHSS). Conditions: Polycystic Ovarian Syndrome, Ovarian Hyperstimulation Syndrome Intervention / Treatment: DRUG: Cabergoline Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: BASIC_SCIENCE Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Development of more than 14 leading follicles larger than 10 mm and serum estradiol more than 3000 pg/ml at the end of ovulation induction with long luteal ovulation induction protocol. * Having the criteria of PCOS Exclusion Criteria: * Not having the inclusion criteria.

Study Objectives This phase II trial studies how well lenalidomide and rituximab work in treating patients with previously untreated stage II, stage III, or stage IV follicular non-Hodgkin lymphoma. Biological therapies, such as lenalidomide, may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Giving lenalidomide together with rituximab may kill more cancer cells. Conditions: Ann Arbor Stage II Grade 1 Contiguous Follicular Lymphoma, Ann Arbor Stage II Grade 1 Non-Contiguous Follicular Lymphoma, Ann Arbor Stage II Grade 2 Contiguous Follicular Lymphoma, Ann Arbor Stage II Grade 2 Non-Contiguous Follicular Lymphoma, Ann Arbor Stage II Grade 3 Contiguous Follicular Lymphoma, Ann Arbor Stage II Grade 3 Non-Contiguous Follicular Lymphoma, Ann Arbor Stage III Grade 1 Follicular Lymphoma, Ann Arbor Stage III Grade 2 Follicular Lymphoma, Ann Arbor Stage III Grade 3 Follicular Lymphoma, Ann Arbor Stage IV Grade 1 Follicular Lymphoma, Ann Arbor Stage IV Grade 2 Follicular Lymphoma, Ann Arbor Stage IV Grade 3 Follicular Lymphoma Intervention / Treatment: OTHER: Laboratory Biomarker Analysis, DRUG: Lenalidomide, BIOLOGICAL: Rituximab 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: * Previously untreated, histologically confirmed follicular lymphoma, World Health Organization (WHO) classification grade 1, 2, or 3a (> 15 centroblasts per high power field with centrocytes present) that is stage III, IV, or bulky (i.e., single mass >= 7 cm in any uni-dimensional measurement) stage II * Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies; fine needle aspirates are not acceptable for diagnosis * Failure to submit pathology specimens within 60 days of patient registration will be considered a major protocol violation * Institutional flow cytometry or immunohistochemistry must confirm CD20 antigen expression * Low or intermediate risk by Follicular Lymphoma International Prognostic Index (FLIPI): 0-2 risk factors * No prior systemic therapy for NHL, including chemotherapy or immunotherapy (e.g., monoclonal antibody-based therapy); patients may have received involved-field radiation therapy * No corticosteroids within two weeks prior to study entry, except for maintenance therapy for a non-malignant disease * Eastern Cooperative Oncology Group (ECOG) performance status =< 2 * Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable; any tumor mass > 1 cm is acceptable * Lesions that are considered non-measurable include the following: * Bone lesions (lesions if present should be noted) * Ascites * Pleural/pericardial effusion * Lymphangitis cutis/pulmonis * Bone marrow (involvement by NHL should be noted) * No known central nervous system (CNS) involvement by lymphoma * Patients with human immunodeficiency virus (HIV) infection are eligible, provided they meet the following * No evidence of coinfection with hepatitis B or C * CD4+ cell count >= 400/mm^3 * No evidence of resistant strains of HIV * If not on anti-HIV therapy, HIV viral load < 10,000 copies HIV RNA/mL * If on anti-HIV therapy, HIV viral load < 50 copies HIV RNA/mL * No history of acquired immune deficiency syndrome (AIDS)-defining conditions * No evidence of active hepatitis B or C infection (i.e., no positive serology for anti-hepatitis B core [HBc] or anti-hepatitis C virus [HCV] antibodies); hepatitis B virus (HBV) seropositive patients (hepatitis B surface antigen positive [HBsAg +]) are eligible if they are closely monitored for evidence of active HBV infection by HBV deoxyribonucleic acid (DNA) testing and receive suppressive therapy with lamivudine or other HBV suppressive therapy until 6 months after the last rituximab dose * Patients with a history of erythema multiforme, toxic epidermal necrolysis or Stevens-Johnson syndrome are not eligible * Patients with uncontrolled seizures are not eligible * Patients with an autoimmune disorder requires active immunosuppression are not eligible * Non-pregnant and non-nursing; females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to registration; further, they must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy; a FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure * No known human anti-chimeric antibody (HACA) positivity * Absolute neutrophil count (ANC) >= 1,000/microliter * Platelet count >= 75,000/microliter * Creatinine clearance >= 30 mL/min unless attributable to NHL; to be calculated by method of Cockcroft-Gault, using actual weight; maximum creatinine clearance (CrCl) 125 mL/min * Total bilirubin =< 2 times upper limit of normal (ULN) unless attributable to NHL or Gilbert disease

Study Objectives The purpose of this study is to assess the efficacy and safety of navarixin (MK-7123) in combination with pembrolizumab (MK-3475) in adults with one of three types of solid tumors: Programmed Death-Ligand 1 (PD-L1) positive refractory non-small cell lung cancer (NSCLC), castration resistant prostate cancer (CRPC) or microsatellite stable (MSS) colorectal cancer (CRC). Conditions: Solid Tumors, Non-small Cell Lung Cancer, Castration Resistant Prostate Cancer, Microsatellite Stable Colorectal Cancer Intervention / Treatment: DRUG: Navarixin, BIOLOGICAL: Pembrolizumab Location: Israel, Canada, Korea, Republic of, United States, Australia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: All Participants * Has one of the following histologically- or cytologically-confirmed advanced/metastatic solid tumors: NSCLC, CRPC, or MSS CRC, by pathology report and has received, or been intolerant to, or has been ineligible for all treatment known to confer clinical benefit. * Has Stage III or Stage IV disease that is not surgically resectable. * Has measurable disease by RECIST 1.1 criteria as assessed by the local site investigator/radiology. * Has supplied tumor tissue from either a newly obtained biopsy or an archival specimen for biomarker analysis. * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Male participants must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period. * Female participants must agree to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment. * Demonstrates adequate organ function. Non-small Cell Lung Cancer (NSCLC) Participants * Has histologically or cytologically confirmed diagnosis of Stage IV metastatic NSCLC. * Has progressed on treatment with an anti-Programmed Death-Ligand 1 (PD-L1) monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies. PD-L1 treatment progression is defined by meeting all of the following criteria: a) Has received >=2 doses of an approved anti-PD-L1 mAb; b) Has demonstrated disease progression after anti-PD-L1 as defined by RECIST 1.1; c) Progressive disease has been documented within 12 weeks from the last dose of anti-PD-L1 mAb. Castration Resistant Prostate Cancer (CRPC) Participants * Has histologically- or cytologically-confirmed adenocarcinoma of the prostate. Components of small cell prostate cancer are permitted. * Has prostate cancer progression on the most recent treatment, as determined by the investigator, by means of one of the following: a) Prostate-Specific Antigen (PSA) progression using local laboratory values as defined by a minimum of 2 rising PSA levels with an interval of >=1 week between each assessment where the PSA value at screening should be >=2 ng/mL; b) Radiographic disease progression in soft tissue based on RECIST 1.1 criteria with or without PSA progression; c) Radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression. * Has progressed on at least one second generation anti-androgen therapy (e.g., enzalutamide, abiraterone). * Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM). Microsatellite Stable Colorectal Cancer (MSS-CRC) Participants * Has a histologically proven locally advanced unresectable or metastatic (Stage IV) CRC. * Has locally confirmed (MSS) CRC; participants with microsatellite instability-high (MSI-H) or microsatellite unstable CRC are not eligible. * Has been previously treated with standard therapies, which must include fluoropyrimidine, oxaliplatin, and irinotecan. Exclusion Criteria: * Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging, clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. * Has had a severe hypersensitivity reaction to treatment with any mAb or components of the study treatment(s). * Has an active autoimmune disease that has required systemic treatment in the past 2 years except vitiligo or resolved childhood asthma/atopy. Participants who have previously been permanently discontinued from PD-(L)1 therapy due to immune related side effects are not eligible for this study. * Has an active infection requiring systemic therapy. * Has symptomatic ascites or pleural effusion. * Has interstitial lung disease that required oral or intravenous glucocorticoids to assist with management. * Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. * Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. Note: Participants who have had a stem cell transplant >5 years ago are eligible as long as there are no symptoms of graft-versus-host disease (GVHD). * Has a known history of human immunodeficiency virus (HIV) infection. * Has a known history of Hepatitis B or known active Hepatitis C virus infection. * Has a history or current evidence of a gastrointestinal condition (e.g. inflammatory bowel disease, Crohn's disease, ulcerative colitis) or impaired liver function or diseases that in the opinion of the Investigator may significantly alter the absorption or metabolism of oral medications; any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, make administration of the study drugs hazardous, or make it difficult to monitor AEs such that it is not in the best interest of the participant to participate, in the opinion of the treating Investigator. * Is pregnant or expecting to conceive or father children within the projected duration of the study. * Has undergone major surgery and has not recovered adequately from any toxicity and/or complications from the intervention prior to starting study treatment. * Has CRPC or MSS CRC and has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. * Has been treated with an agent directed to another stimulatory or co-inhibitory Tcell receptor (e.g. cytotoxic T-lymphocyte protein 4 [CTLA-4], tumor necrosis factor receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor superfamily member 9 [CD137]). * Has received prior systemic anti-cancer therapy including investigational agents or has used an investigational device within 28 days prior to the first dose of study treatment. * Has received prior radiotherapy (not to target lesions) within 2 weeks of start of study treatment. * Is expected to require any other form of antineoplastic therapy while on study. * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy in excess of replacement doses (prednisone <=10 mg/day is acceptable), or on any other form of immunosuppressive medication. * Has received a live-virus vaccine within 30 days prior to first dose of study treatment. * Has been previously treated with a chemokine receptor 2 (CXCR2) inhibitor (e.g. AZD5069, reparixin, danirixin, LY3041658 Ab, HuMax-IL8, etc.).

Study Objectives Letrozole is a chemical compound, CGS 20267 which is a third-generation, nonsteroidal aromatase inhibitor. Letrozole blocks estrogen synthesis by directly affecting the hypothalamic-pituitary-ovarian axis, subsequently, increases gonadotropins which increase pregnancy rates. Possible positive outcomes of aromatase inhibitors over selective estrogen-receptor modulators include a more physiologic hormonal stimulation of the endometrium which increases receptivity, a lower multiple-pregnancy through single follicle growth, a lesser side-effect especially vasomotor and mood symptoms, and more prompt clearance from blood, hence, reducing the probabilities of periconceptional exposure Conditions: PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries Intervention / Treatment: DRUG: Letrozole tablets Location: Egypt Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * Infertile women with PCOS * Normal hysterosalpingography * Normal semen analysis according to WHO parameters are major prerequisites Exclusion Criteria: * Infertile women with causes other than PCOS, * Ages <18 or >35 years * women taken confounding medications like other infertility drugs * Insulin sensitizers or hormones * Abnormal hysterosalpingography * Subnormal semen analysis

Study Objectives Hypothesis: AR-67 (formerly DB-67) represents a rationally engineered drug that possesses improved stability, toxicity, and efficacy compared to current Food and Drug Administration (FDA)-approved camptothecins, based on the extensive research of prior studies. Therefore, the investigators hypothesize that AR-67 (formerly DB-67) will be well-tolerated and efficacious in phase I clinical trials. This initial phase I trial will establish the maximum tolerated dose in humans, establish the toxicity profile, and define the appropriate dose of AR-67 (formerly DB-67) for future phase II and III clinical trials. Conditions: Tumors Intervention / Treatment: DRUG: AR-67 (formerly DB-67) 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: * >18 year old subjects with solid malignancies that have progressed after at least one prior chemotherapy regimen and have exhausted other therapies * Treated and clinically stable brain metastases * Measurable OR non-measurable disease * Greater than three weeks since surgery * Normal organ and marrow function * ECOG Performance Status of < 2 * No other prior malignancy except for treated basal cell or squamous cell skin cancer, in situ cervical cancer, Stage I or II cancer (patient in complete remission) or other cancer from which the patient has been disease-free for 5 years. * Computed tomography (CT) scan of involved areas within 28 days of registration * Life expectancy of greater than 12 weeks. Exclusion Criteria: * Pregnant or nursing females * Chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) of entering the study. * Patients may not be receiving any other investigational agent. Uncontrolled intercurrent illness including active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Allergic reactions to compounds of similar chemical or biologic composition to DB-67 (i.e. camptothecins such as irinotecan, topotecan, or others of this class of pharmaceuticals). * Subjects with prior anaphylactic injection reaction of > grade 3 to paclitaxel or any other product formulated with cremophor * Subjects with HIV

Study Objectives This study will evaluate the efficacy and safety of 6-mercaptopurine (6MP) in combination with methotrexate (MTX) in patients with breast or ovarian cancer who are known to have a BRCA (breast cancer gene) mutation. Conditions: Breast Cancer, Ovarian Cancer Intervention / Treatment: DRUG: 6-Mercaptopurine, DRUG: Methotrexate Location: United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with proven BRCA1 or BRCA2 mutations and after appropriate exposure to standard treatment, as defined by: Breast Cancer * Patients with initially histologically or cytologically proven locally advanced or metastatic breast cancer who may have received up to 3 previous lines of chemotherapy in the locally advanced or metastatic breast cancer setting. * Patients must have previously had a taxane and an anthracycline in either the adjuvant or metastatic setting, provided that these were not contraindicated. * Patients with hormone responsive disease should have had at least 1 line of hormone therapy for metastatic disease. * Prior treatment with a poly-Adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitor is permissible. OR Ovarian Cancer * Patients with initially histologically or cytologically proven ovarian cancer. * Patients must have disease that is platinum resistant or in whom further platinum based therapy is inappropriate. * Prior treatment with a PARP inhibitor is permissible. * Patients must have measurable disease on computerized tomography (CT) or Magnetic resonance imaging (MRI) scan as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. * Age >=18 years. * Eastern Cooperative Oncology Group (ECOG) performance score of 0-2. * Life expectancy >12 weeks. * Written informed consent. * Patient willing and able to comply with all protocol requirements. * No prior anti-cancer treatment in previous 4 weeks, other than palliative radiotherapy (RT). * Haematological and biochemical indices within the ranges shown below. * Laboratory Test Value required * Haemoglobin (Hb) > 10g/dL * White Blood Count (WBC) > 3x109/L * Platelet count > 100,000/μL * Absolute Neutrophil count > 1.5x109/L; * Serum bilirubin <= 2 x Upper limit normal (ULN) * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) and alanine aminotransferase (ALT) or ALT <= 5 x ULN (liver metastasis) * or <= 3 x ULN (no liver metastasis) * Alkaline phosphatase <= 5 x ULN * Serum creatinine <= 1.5 x ULN * Ascites and pleural effusions must be drained prior to therapy. Exclusion Criteria: * Patients with any of the following contra-indications to thiopurines (6MP or 6TG) or methotrexate: * family history of severe liver failure; * alcoholism; * porphyria; * diffuse infiltrative pulmonary or pericardial disease; * known hypersensitivity to either trial agent. * Patients found to have a Low/Low genotype on thiopurine methyltransferase (TPMT) testing will be excluded. * Pregnant or breast-feeding women or women of childbearing potential unless highly effective methods of contraception are used. * Other active malignancy, with the exception of adequately treated in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. * Patients known or tested to be serologically positive for Hepatitis B, Hepatitis C or human immunodeficiency virus (HIV). * Patients with active central nervous system (CNS) lesions are excluded (i.e., those with radiographically unstable, symptomatic lesions). However, patients treated with stereotactic therapy or surgery and/or whole brain radiotherapy are eligible if the patient remains without evidence of disease progression in brain >= 3 months prior to registration date . They must also be off corticosteroid therapy for >= 3 weeks prior to registration date. * Patients who have received anticancer agent(s) or an investigational agent within 28 days prior to study drug administration. * Subjects who have not recovered to within one grade level (not to exceed grade 2) of their baseline following a significant adverse event or toxicity attributed to previous anticancer treatment are excluded.

Study Objectives The purpose of this study is to determine whether TRC105 in combination with Bevacizumab is effective in the treatment of two patients with metastatic and refractory choriocarcinoma. Conditions: Choriocarcinoma Intervention / Treatment: BIOLOGICAL: TRC105, BIOLOGICAL: 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: * Willingness and ability to consent for self to participate in study * Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures * Measurable disease by RECIST 1.1 and elevated serum β-hCG * Histologically proven choriocarcinoma that has progressed despite all described lines of chemotherapy for this condition Exclusion Criteria: * Prior treatment with TRC105 * Serious dose-limiting toxicity related to prior bevacizumab * Current treatment on another therapeutic clinical trial * Uncontrolled chronic hypertension defined as systolic > 140 or diastolic > 90 despite optimal therapy (initiation or adjustment of BP medication prior to study entry is allowed provided that the average of 3 BP readings at a visit prior to enrollment is < 140/90 mm Hg) * Symptomatic pericardial or pleural effusions * Uncontrolled peritoneal effusions requiring paracentesis more frequently than every 2 weeks * Active bleeding or pathologic condition that carries a high risk of bleeding (i.e. hereditary hemorrhagic telangiectasia) * Thrombolytic or anticoagulant use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy * Cardiac dysrhythmias of NCI CTCAE grade >= 2 within the last 28 days * Known active viral or nonviral hepatitis * Open wounds or unhealed fractures within 28 days of starting study treatment * History of peptic ulcer disease or erosive gastritis within the past 6 months, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD) within 28 days of starting study treatment * Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness * Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for this study

Study Objectives This study has the following objectives: Primary Objective * To evaluate the anti-lymphoma efficacy of daily oral doses of ITF2357 followed by intravenous Mechlorethamine administered to patients with refractory/relapsed Hodgkin's lymphoma. Secondary Objective - To evaluate the safety and tolerability of multiple courses of ITF2357 followed by Mechlorethamine in a population of chemotherapy pretreated patients. Conditions: Hodgkin's Lymphoma Intervention / Treatment: DRUG: ITF2357 Location: Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Written Informed Consent; * Age >=18 years; * Histologically confirmed diagnosis of Hodgkin's lymphoma; * Subjects who have failed second-line or subsequent-line salvage chemo- radiotherapy regimens for whom no other treatment options of proven efficacy can be given; * Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements; * ANC >=1500/µL; Platelet count >=75000/µL; * Hemoglobin >=9 g/dL (may not be transfused or treated with erythropoietin to maintain or exceed this level); * Total bilirubin <=1.6 mg/dL; AST or ALT <=2.5 times the upper limit of normal; * Serum creatinine <=2.0 mg/dL or creatinine clearance >50 mL/min; * Serum Potassium and Magnesium within normal limits; * Subjects with at least one bi-dimensional lesion measurable by CT-scan or MRI, according to the Revised Response Criteria for Malignant Lymphoma of the International Working Group (J Clin Oncol, 25:579-586, 2007); * ECOG performance status of 0 or 1; * Use of an effective means of contraception for women of childbearing potential and men with partners of childbearing potential; * Life expectancy of >3 months; * Subjects receiving intravenous Mechlorethamine (6 mg/sqm) as single agent at least 4 weeks before study entry; * Willingness and capability to comply with the requirements of the study. Exclusion Criteria: * Active bacterial or mycotic infection requiring antimicrobial treatment * Pregnancy or lactation * Anticancer chemotherapy or radiotherapy during the study or within 4 weeks of study entry. * A marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval > 450 ms, according to Bazett's correction formula - see appendix I for the formula) * Use of concomitant medications that prolong the QT/QTc interval (see appendix H for full list) * Clinically significant cardiovascular disease including: * Uncontrolled hypertension, myocardial infarction, unstable angina * New York Heart Association (NYHA) Grade II or greater congestive heart failure * History of any cardiac arrhythmia requiring medication (irrespective of its severity) * A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) * Positive blood test for HIV, HBV and HCV * Identification of viral DNA by quantitative PCR for EBV and JC virus. * History of other diseases, metabolic dysfunctions, physical examination findings, or clinical laboratory findings giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk from treatment complications

Study Objectives Open label study of sorafenib Conditions: Lung Cancer Intervention / Treatment: DRUG: sorafenib 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: * Age > 18 * Life expectancy > 12 weeks * Biopsy-proven BAC or adenocarcinoma * Willing to provide smoking status * Selected IIIB or stage IV cancer that is incompletely resected or unresectable Exclusion Criteria: * O2 saturation < 88% on room air * Pregnant or nursing women * Surgery or radiation therapy within 4 weeks of starting study * Major heart condition within 6 months of starting therapy * Certain concomitant medications prohibited

Study Objectives PARC is an international phase I/II trial evaluating the safety and activity of pegylated recombinant human arginase (BCT-100) in children and young people with relapsed/refractory leukaemia, neuroblastoma, sarcoma and high grade gliomas (brain cancers). Currently the outcomes for these patients are poor and the therapeutic options are limited with a significant toxicity burden. Therefore new treatments which work in different ways to standard chemotherapy are urgently needed. Research has shown that arginine (a nutrient) is important in the survival of cancer cells. BCT-100 is a drug which can deplete arginine levels and starve cancer cells - a completely new approach. BCT-100 has been tested in adults and shown to be active with almost no side-effects. This trial will test whether this dose of BCT-100 is also safe and active in children with relapsed/refractory leukaemia, neuroblastoma, sarcoma and high grade glioma. The trial will also study how BCT-100 is broken down in the body and look for new biological markers of treatment response. Up to 64 children with relapsed cancers will be recruited over 2 years. Conditions: Cancer, Pediatric Solid Tumor, Pediatric AML, Pediatric ALL Intervention / Treatment: DRUG: PEG- BCT-100 Location: Australia, Netherlands, United Kingdom Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Aged 1- <25 years old at the time of study registration * Histologically confirmed disease in one of the following four groups: * Group 1 - Acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) * Group 2 - Neuroblastoma Group 3 - Sarcoma * Group 4 - High grade glioma (as defined by 2016 WHO CNS classification) * Radiological or laboratory evidence of disease progression (during or after completion of first line treatment) or any subsequent recurrence (biopsy at relapse is not mandated). * Measurable bone marrow disease (group 1) or at least one evaluable radiological site of disease (group 2, 3 and 4). * Adequate liver function defined as a total bilirubin <=1.5x the upper limit of normal for age and ALT <= 3x the upper limit of normal for age * Documented negative pregnancy test for female patients of childbearing potential within 7 days of trial entry * Sexually active patients must agree to use adequate and appropriate contraception while on study drug and for 12 months following treatment discontinuation * Written informed consent given by patient and/or parents/legal representative Exclusion Criteria: * Previous treatment with another therapeutic arginine depleting drug (bacterial or human) or arginase inhibitor * Presence of any >= CTCAE grade 3 clinically significant treatment-related toxicity from prior therapies * Pregnant or lactating female * Evidence of uncontrolled infection

Study Objectives The primary purpose of this study is to determine the safety and feasibility of delivering HDMTX in an outpatient setting. Conditions: Osteosarcoma Intervention / Treatment: DRUG: High Dose Methotrexate Location: Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * >= 6 years of age; * Localized or metastatic osteosarcoma; * Adequate renal function (GFR > 70 ml/1.73m2) prior to each cycle; * No grade III/IV renal toxicity, mucositis or vomiting with most recent prior inpatient MTX cycle; * Parent and/or patient must be able to provide written consent, and complete Patient Flow Sheets in English. Exclusion Criteria: * Patients, in the opinion of the primary healthcare team, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal. * Pregnant females * Breastfeeding females

Study Objectives To explore the intervention effect of auricular point sticking on chemotherapy-induced taste alterations in cancer patients, and analyze its relationship with quality of life, nutritional status and psychology of patients. Conditions: Dysgeusia, Acupressure, Chemotherapy Effect Intervention / Treatment: BEHAVIORAL: auricular point sticking Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Patients with malignant tumors diagnosed by histopathology or pathology; * Age >=18 years old; * Patients who received platinum-based chemotherapy and completed at least one cycle of chemotherapy; * According to the chemotherapy-induced taste Changes Scale (CiTAS), the score of patients was >=6; * Patients voluntarily participated in the treatment with good compliance and adherence. Exclusion Criteria: * Patients with treatment plan adjustment or concurrent radiotherapy; * Patients with abnormal taste and malnutrition caused by various reasons before chemotherapy; * Patients with inflammation of the external ear or eczema, ulcers, chilblain in the pressing area; * Allergic or intolerant to adhesive stickers; * Those who were lost to follow-up or withdrew voluntarily; * Patients enrolled in other studies at the same time.

Study Objectives This randomized phase II trial is studying how well giving pazopanib with or without bicalutamide works in treating patients with prostate cancer that did not respond to hormone therapy. Pazopanib 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. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, may lessen the amount of androgens made by the body. Giving pazopanib hydrochloride together with bicalutamide may be an effective treatment for prostate cancer. Conditions: Hormone-Resistant Prostate Cancer, Recurrent Prostate Carcinoma Intervention / Treatment: DRUG: Bicalutamide, OTHER: Laboratory Biomarker Analysis, DRUG: Pazopanib Hydrochloride, OTHER: Pharmacological Study Location: Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed prostate cancer * Must have received prior hormonal therapy, including either medical (luteinizing hormone-releasing hormone [LHRH] agonist) or surgical (orchiectomy) castration * Castrate level of testosterone (< 50 ng/dL) * Patients treated with LHRH agonists must continue or restart this therapy * Must have radiological documentation of either measurable or non-measurable disease * Must show documented progression of prostate cancer while on hormonal therapy as indicated by PSA increase * Rising PSA is defined as <= 2 consecutive rises in PSA taken >= 1 week and <= 2 months apart * PSA >= 5 ng/mL * No known brain metastases * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS 60-100% * Life expectancy > 3 months * White blood cell (WBC) >= 3,000/mm^3 * Absolute neutrophil count (ANC) >= 1,500/mm^3 * Platelet count >= 100,000/mm^3 * International normalized ratio (INR) =< 1.2 * Activated partial thromboplastin time (PTT) =< 1.2 times upper limit of normal (ULN) * Bilirubin normal * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 1.5 times ULN * Creatinine normal OR creatinine clearance >= 60 mL/min * Fertile patients must use effective contraception * No history of allergic reactions attributed to compounds of similar chemical or biological composition to pazopanib hydrochloride or bicalutamide * Proteinuria =< 1+ on 2 consecutive dipsticks taken >= 1 week apart * QTc < 480 msec * No significant electrocardiogram (ECG) abnormalities * No poorly controlled hypertension (systolic blood pressure [BP] > 150 mm Hg or diastolic BP > 90 mm Hg) * No condition (e.g., gastrointestinal [GI] tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation; prior surgical procedures affecting absorption; or active peptic ulcer disease) that impairs the ability to swallow and retain pazopanib hydrochloride tablets * No serious or nonhealing wound, ulcer, or bone fracture * No abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within the past 28 days * No cerebrovascular accident within the past 6 months * No myocardial infarction, cardiac arrhythmia, admission for unstable angina, cardiac angioplasty, or stenting within the past 12 weeks * No venous thrombosis within the past 12 weeks * No New York Heart Association (NYHA) class III-IV heart failure * Patients with a history of NYHA class II heart failure who are asymptomatic on treatment are eligible * No concurrent uncontrolled illness, including, but not limited to, ongoing or active infection * No psychiatric illness or social situation that would preclude study compliance * Recovered from all prior therapy * Prior neoadjuvant or adjuvant chemotherapy allowed * More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy * At least 4 weeks since prior antiandrogens * At least 4 weeks since prior surgery * No prior bicalutamide therapy lasting > 3 months in duration * Concurrent steroids allowed if no change in steroid dosage within the past 4 weeks * No other concurrent investigational agents * No concurrent therapeutic warfarin * Concurrent low molecular weight heparin or prophylactic low-dose warfarin allowed * No concurrent combination antiretroviral therapy for human immunodeficiency virus (HIV)-positive patients

Study Objectives The purpose of this study is to determine the tolerability of ME-344, find the maximum tolerated dose, and the safety profile in patients with refractory solid tumors. Conditions: Solid Tumors Intervention / Treatment: DRUG: ME-344 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: * Provision of informed consent * Male or female >= 18 years of age * Histologic or cytologic confirmed locally advanced or metastatic cancer that has no standard therapeutic alternatives. * ECOG Performance status 0-1 (Appendix A) * A minimum life expectancy of 12 weeks * Adequate bone marrow, hepatic and renal function as evidenced by: * Absolute neutrophil count (ANC) > 1.5 x 109/L * Platelet count > 100 x 109/L * Hemoglobin > 9.0 g/dL * Serum bilirubin < 1.5 x ULN * AST/ALT (SGOT/SGPT) < 2.5 x ULN for the reference laboratory or < 5 x ULN in the presence of liver metastases * Serum creatinine < 1.5 x ULN * Adequate cardiac function as evidenced by: * CK-MB within normal levels at baseline * Troponin T within normal levels at baseline * The average QTc from triplicate screening ECGs (every 5 minutes over a total of 15 minutes) must be < 470 msec to be eligible for the study. (If a patient has an average QTc interval >470 msec at screening, the screening ECG may be repeated twice (at least 24 hours apart). * LV Ejection Fraction > lower limit of institutional normal level * All potentially fertile patients will agree to use an effective form of contraception during the study and for 30 days following the last dose of ME-344 (an effective form of contraception is defined as an oral contraceptive or a double barrier method). * At least 4 weeks must have elapsed prior to Day 1 Cycle 1 since prior chemotherapy (6 weeks for nitrosourea or mitomycin C), investigational drug or biologic therapy and any toxicity associated with these treatments has recovered to <= NCI-CTCAE Grade 1. * At least 21 days must have elapsed prior to Day 1 Cycle 1, radiotherapy, immunotherapy or following major surgery and any surgical incision should be completely healed. At least 14 days must have elapsed prior to Day 1 Cycle 1 for "limited palliative radiotherapy", defined as a course of therapy encompassing <25% total bone marrow volume and not exceeding 30 Gy. Exclusion Criteria: * Patients who are pregnant or breastfeeding * Tumor involvement of the Central Nervous System (CNS): * Patients with treated and stable CNS metastases may be eligible to participate after discussion and approval from the Medical Monitor * Uncontrolled infection or systemic disease. * Clinically significant cardiac disease not well controlled with medication (e.g., congestive heart failure, symptomatic coronary artery disease e.g. angina, and cardiac arrhythmias) or myocardial infarction within the last 12 months. * Any major surgery, radiotherapy, or immunotherapy within the last 21 days. Limited palliative radiation, defined as encompassing <25% of total bone marrow volume and not exceeding a total dose of 30 Gy, within the last 14 days. * Chemotherapy regimens with delayed toxicity within the last 4 weeks (or within 6 weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens given continuously or on a weekly basis with limited potential or delayed toxicity within the last 2 weeks. * No concurrent systemic chemotherapy or biologic therapy is allowed. * Known hypersensitivity to any components of ME-344 study drug product. * Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both). * History of solid organ transplantation. * Psychiatric disorder or social or geographic situation that would preclude study participation.

Study Objectives The purpose of this research study is to evaluate safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of the investigational drug PLX2853 in subjects with advanced malignancies. Conditions: Small Cell Lung Cancer, Uveal Melanoma, Ovarian Clear Cell Carcinoma, Non-Hodgkin Lymphoma, Advanced Malignancies, Solid Tumor, Diffuse Large B Cell Lymphoma, Follicular Lymphoma Intervention / Treatment: DRUG: PLX2853 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: * Confirmed diagnosis of one of the following: * Phase 1b: * Histologically confirmed advanced refractory solid tumor that is measurable or evaluable per RECIST 1.1 criteria. * Histologically confirmed NHL: diffuse large B-cell lymphoma and follicular lymphoma (Grade 1-3A) which is measurable or evaluable per Lugano criteria, has progressed following at least 1 line of prior anticancer therapy. * Phase 2a: Patients with various solid tumors or NHL who have received prior therapy. * Age >=18 years * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 * Adequate organ function as appropriate for the disease under study. All screening laboratory tests should be performed within 10 days of treatment initiation. * Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test at Screening (<=7 days prior to 1st study drug dose) and must agree to use an effective form of contraception from the time of the negative pregnancy test up to 90 days after the last dose of study drug. Effective forms of contraception include abstinence, hormonal contraceptive in conjunction with a barrier method, or a double barrier method. Women of non-child-bearing potential may be included if they are either surgically sterile or have been postmenopausal for >=1 year. * Fertile men must agree to use an effective method of birth control during the study and for up to 90 days after the last dose of study drug. * All associated clinically significant drug-related toxicity from previous cancer therapy must be resolved prior to study treatment administration (alopecia, erectile impotence, hot flashes, decreased libido, and neuropathy is allowed). * Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements Exclusion Criteria: * Prior exposure to a bromodomain inhibitor, such as OTX-015 or CPI-0610 * Known uncontrolled fungal, bacterial, and/or viral infection >=Grade 2 * Autoimmune hemolytic anemia or autoimmune thrombocytopenia * Presence of symptomatic or uncontrolled central nervous system or leptomeningeal metastases * Known or suspected allergy to the investigational agent or any agent given in association with this trial * Clinically significant cardiac disease such as cardiac arrhythmias including bradyarrhythmias and/or subjects who require anti-arrhythmic therapy (excluding beta blockers or digoxin), including uncontrolled hypertension or arterial or venous thrombotic events. Subjects with controlled atrial fibrillation are not excluded. * Inability to take oral medication or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the Investigator, would preclude adequate absorption * Non-healing wound, ulcer, or bone fracture * Subject has known human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection or is known to be a carrier of hepatitis B or C. Subjects who are positive for hepatitis C virus (HCV) antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible. Subjects with occult or prior hepatitis B virus (HBV) infection (defined as positive total hepatitis B core antibody (HBcAb) and negative hepatitis B surface antigen (HBsAg) may be included if HBV DNA is undetectable. These subjects must be willing to undergo additional testing per local standard of care. * Active second malignancy with the exception of any of the following: * Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer; * Adequately treated Stage I cancer from which the subject is currently in remission and has been in remission for >=2 years; * Low-risk prostate cancer with Gleason score <7 and prostate-specific antigen <10 ng/mL; or * Any other cancer from which the patient has been disease-free for >=3 years. * Subjects with documented hepatic metastases involving >50% of the hepatic parenchyma, or any individual liver metastasis >5 cm, as assessed by the investigator. * Major surgery or significant traumatic injury within 14 days prior to Cycle 1 Day 1 * Receipt of anti-cancer therapy with insufficient washout prior to Cycle 1 Day 1: No chemotherapy, radiation therapy, or small molecule tyrosine kinase inhibitors (TKI) for the treatment of cancer within 14 days or 5 half-lives (whichever is shorter) of Cycle 1 Day 1. Certain standard of care hormonal anticancer therapies, such as agents targeted to GnRH for the treatment of prostate cancer or aromatase inhibitors for the treatment of breast cancer, may be permitted after consultation with the medical monitor. No immune therapy or other biologic therapy (other monoclonal antibodies or antibody-drug conjugates [ADCs]) for the treatment of cancer within 28 days of Cycle 1 Day 1. * Subject is receiving systemic steroids at doses greater than the equivalent of prednisone 10 mg daily, with the exception of intermittent use for the treatment of emesis * Subject is participating in any other therapeutic clinical study (observational or registry trials are allowed) * Female subjects who are pregnant or breast-feeding * Presence of any other medical, psychological, familial, sociological, or geographic condition potentially hampering compliance with the study protocol or would interfere with the study endpoints or the subject's ability to participate in the study in the judgement of the investigator

Study Objectives This is a 2-part prospective trial examining the ability of Stereotactic Body Radiation Therapy (SBRT) to induce a response to MK-3475, a humanized antibody to PD-1, in patients who progress on this antibody. Patients with metastatic melanoma will be enrolled after they have progressed on anti-PD-1 therapy. Patients with metastatic NSCLC (previously untreated with anti-PD-1 or anti-PD-L1 therapy) will be enrolled and treated with MK-3475 until they exhibit progression of disease. At this point (when patients have demonstrated progression of disease) a single target lesion will be selected and treated with SBRT, and then MK-3475 will be restarted and continued until there is further progression of disease. The first phase of the study is a radiation dose escalation with a constant dose of MK-3475. The second part of the study includes expansion cohorts of NSCLC and melanoma patients. Conditions: Melanoma, Lung Cancer Intervention / Treatment: DRUG: MK-3475, RADIATION: Stereotactic Body Radiation Therapy (SBRT) Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Be willing and able to provide written informed consent/assent for the trial. * Have metastatic melanoma or NSCLC, or locally advanced NSCLC not suitable for curative-intent local therapy. * For melanoma patients and NSCLC patients treated with prior anti-PD-1 therapy, patients must have received prior PD-1 therapy and have progressed (irPD) by irRC. * Have 2 or more measurable sites of disease as defined by either RECIST 1.1, or cutaneous lesions at least 1 cm in greatest dimension * Have at least one site of disease that is considered potentially suitable for treatment with SBRT * Have provided tissue from an archival or newly obtained tissue sample of a tumor lesion, sufficient for analysis of PD-L1 and other biomarkers. Patients who have had PD-L1 analysis previously performed at Merck can substitute earlier analysis results and are not required to submit additional tissue for PD-L1 testing. Expression of PD-L1 is NOT required for study entry. * Have a performance status of 0, 1 or 2 on the ECOG Performance Scale. * Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 28 days of protocol treatment. Table 1. Adequate Organ Function Laboratory Values (System/Laboratory Value) Hematological * Absolute neutrophil count (ANC) >=1,500 /mcL * Platelets >=100,000 / mcL * Hemoglobin >=9 g/dL Renal * Measured or calculated creatinine** clearance <=1.5 X upper limit of normal (ULN) * (GFR can also be used in place of creatinine or CrCl) >=60 mL/min for subject with creatinine levels > 1.5 X institutional ULN Hepatic * Serum total bilirubin <= 1.5 X ULN OR * Direct bilirubin Direct bilirubin <= ULN for subjects with total bilirubin levels > 1.5 ULN * AST (SGOT) and ALT (SGPT) <= 2.5 X ULN OR <= 5 X ULN for subjects with liver metastases **(Creatinine clearance should be calculated per institutional standard. ) * Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. * Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. * Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy Exclusion Criteria: * Has had radiation therapy within 2 weeks of the first protocol treatment. * Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 2 weeks of the first protocol treatment. * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks of the first protocol treatment. The use of low-dose steroids for management of chronic conditions is allowed. * Non-small cell lung cancer patients enrolling to MK-3475 as first protocol therapy (no prior anti-PD-1 therapy): Has had a prior monoclonal antibody within 4 weeks prior to first protocol treatment or who has not recovered (i.e., <= Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. * Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks of the first protocol treatment or who has not recovered (i.e., <= Grade 1 or at baseline) from adverse events due to a previously administered agent. * Note: Subjects with <= Grade 2 neuropathy are an exception to this criterion and may qualify for the study. * Note: Patients who have had prior treatments with Tyrosine Kinase Inhibitors (e.g. Tarceva) require only a 72-hour washout period prior to starting protocol treatment. * Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. * Has known active and untreated brain (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate. * Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an example of an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Those with a history of hypothyroidism who are now stable on hormone replacement will not be excluded. Those with Sjorgen's syndrome will not be excluded from the study. * Has a history of (non-infectious) pneumonitis that required steroids, current pneumonitis or evidence of interstitial lung disease. * 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. * 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. * Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). * Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). * Has received a live vaccine within 30 days prior to the first protocol treatment.

Study Objectives The purpose of this open label, two stage, phase II study is to evaluate the efficacy and tolerability of ZD6474 in patients with locally advanced or metastatic hereditary medullary thyroid carcinoma. Conditions: Thyroid Cancer Intervention / Treatment: DRUG: ZD6474 (vandetanib) Location: United States, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Locally advanced or hereditary medullary thyroid cancer * Signed informed consent * One or more measurable lesions Exclusion Criteria: * Brain metastases or spinal cord compression * Specific laboratory ranges * Specific heart problems * Prior chemotherapy and/or radiation therapy * Participation in other trials within 30 days

Study Objectives This double-blind, placebo-controlled study will evaluate the benefit of first-line maintenance erlotinib (Tarceva) versus erlotinib at the time of disease progression in participants with advanced NSCLC who have not progressed following 4 cycles of platinum based-chemotherapy and whose tumor does not harbor an epidermal growth factor receptor (EGFR)-activating mutation. Participants will be randomized to receive either erlotinib 150 milligrams (mg) orally (PO) once daily or placebo. Participants who progress on placebo will receive erlotinib 150 mg PO once daily as second-line therapy, and those who progress on erlotinib may switch to a non-investigational, second-line chemotherapy. Treatments will continue until disease progression, death, or unacceptable toxicity. Participants may also be entered into a final Survival Follow-Up (SFU) period upon treatment discontinuation. Conditions: Non-Squamous Non-Small Cell Lung Cancer Intervention / Treatment: DRUG: Placebo, DRUG: Erlotinib, DRUG: Second-Line Chemotherapy Location: Hungary, Canada, Lithuania, United States, Taiwan, France, Poland, Thailand, Italy, Netherlands, Ukraine, South Africa, Bulgaria, Brazil, China, Latvia, Czech Republic, Korea, Republic of, Romania, Slovakia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Adults greater than or equal to (>=) 18 years of age, or legal age of consent if greater than 18 * Advanced or recurrent (Stage IIIB) or metastatic (Stage IV) NSCLC * Completion of 4 cycles of platinum-based chemotherapy without progression (end of last chemotherapy cycle less than or equal to [<=] 28 days prior to randomization) * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Exclusion Criteria: * Prior exposure to agents directed at human epidermal growth factor receptor (HER) axis (e.g. erlotinib, gefitinib, cetuximab) * Participants whose tumors harbor an EGFR-activating mutation * Prior chemotherapy or therapy with systemic anti-neoplastic therapy for advanced disease before Screening * Use of pemetrexed in maintenance setting (pemetrexed allowed during the chemotherapy run-in) * Participants who have undergone complete tumor resection after responding to the platinum-based chemotherapy during the Screening phase * Any other malignancies within 5 years, except for curatively resected carcinoma in situ of the cervix, basal or squamous cell skin cancer, ductal carcinoma in situ, or organ-confined prostate cancer * Central nervous system (CNS) metastases or spinal cord compression that has not been definitely treated with surgery and/or radiation, or treated CNS metastases or spinal cord compression without stable disease for >=2 months * Human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection * Any inflammatory changes of the surface of the eye

Study Objectives That panitumumab in combination with Epirubicin, Cisplatin and Capecitabine (ECX) will safely decrease the frequency of pT3/T4 below that of ECX alone in subjects with locally advanced adenocarcinoma of the stomach and gastroesophageal junction. Conditions: Stomach Neoplasms, Gastroesophageal Junction Neoplasms Intervention / Treatment: DRUG: Epirubicin, Cisplatin, Capecitabine, Panitumumab, DRUG: Epirubicin, Cisplatin, Capecitabine Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Competent to comprehend, sign, and date an IEC-approved informed consent form, written informed consent. * Of either gender and aged 18 years or more. * Diagnosed with histologically confirmed adenocarcinoma of the stomach or the gastroesophageal junction of Type I/II/III according to the classification of Siewert et al, 1996. * Stage uT/3 or 4 N0/+ and M0 disease evaluated by endoscopic ultrasound, spiral computed tomography of the chest, abdomen and pelvis and by laparoscopy in uT3/T4 tumors. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Leucocyte count > 3,000/mm3. * Platelet count >=100,000/mm3. * Haemoglobin >=10 g/dl. * Serum creatinine <= 1.5x of upper limit of normal (ULN). * Creatinine clearance > 60 ml/kg/min measured either by 24-h urine sampling or calculated by using the Cockcroft-Gault formula . * Aspartate aminotransferase (AST) <=3 x ULN. * Alanine aminotransferase (ALT) <=3 x ULN. * Bilirubin <= 1.5 x ULN. * Magnesium >= lower limit of normal. * Calcium >= lower limit of normal. * Subject is deemed a good candidate for surgery. Exclusion Criteria: * Any metastatic disease. * Other malignant tumours less than five years old. Exceptions include basocellular carcinoma, in situ cancer of the cervix of the uterus, or any curatively-treated other malignancies without evidence of disease for more than five years. * Significant ascites or pleural effusion. * Prior anti-EGFr antibody therapy (e.g. cetuximab) or treatment with small molecule EGFr tyrosine kinase inhibitors (e.g. erlotinib). * Prior chemotherapy, radiotherapy or antibody therapy for gastric cancer or cancer of the gastro-oesophageal junction. * Concomitant therapy with sorivudine or analogue compounds. * Known previous or ongoing abuse of narcotic drug, other medication or alcohol. * Significant cardiovascular disease including New York Heart Association (NYHA) grade II or greater congestive heart failure, peripheral arterial occlusive disease stage II or greater, symptomatic coronary heart disease, insufficiently treated arterial hypertension, unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia. * History or evidence upon physical examination of CNS disease unless adequately treated, seizure not controlled with standard medical therapy, or history of stroke. * History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest CT scan. * Pre-existing polyneuropathy grade >1 according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), except for loss of tendon reflex as the only symptom. * Treatment for systemic infection within 14 days before initiating study treatment. * Active inflammatory bowel disease, serious gastric ulceration or other bowel disease causing chronic diarrhoea (defined as > 4 loose stools per day). * Suspected or known dihydropyrimidine dehydrogenase deficiency (DPD). * Thrombosis or severe bleeding within six months prior to entry into the study (except for bleeding of the tumour before its surgical resection), evidence of bleeding diathesis or coagulopathy, or current or recent (within 10 days prior to initiation of study treatment) use of full-dose oral or parenteral anticoagulants for therapeutic purposes. * History of any medical condition that may increase the risks associated with study participation or may interfere with the interpretation of the study results. * Known positive test for human immunodeficiency virus infection, hepatitis C virus or chronic active hepatitis B infection. * Known allergy to the investigational product, to any of its excipients, to monoclonal antibodies, or to any of the components of the chemotherapy regimen. * Any co-morbid disease that would increase risk of toxicity. * Any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures. * Any investigational agent or participation in another clinical trial within 30 days prior to randomisation. * Must not have had a major surgical procedure within 28 days of randomisation. * Subject who is pregnant or breast feeding. * Woman or man of childbearing potential not consenting to use adequate contraceptive precautions (intrauterine contraceptive device, contraceptive implants, injectables (hormonal depot), transdermal hormonal contraception (contraceptive patch), sexual abstinence or vasectomised partner) during the course of the study and for six months after the last study drug administration for women and men. Post-menopausal women must have been amenorrheic for at least 12 months to be considered of non-child-bearing potential. * Subject unwilling or unable to comply with study requirements. * Hearing impairment

Study Objectives The purpose of this research study is to determine the highest dose of a drug called bortezomib that can be given with a drug called G-CSF before stem cell collection to help in the mobilization of stem cells. Conditions: Multiple Myeloma Intervention / Treatment: BIOLOGICAL: Bortezomib, DRUG: G-CSF 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: * Histologically confirmed diagnosis of multiple myeloma. * Eligible for autologous transplantation. * Received at least two cycles of any regimen as initial systemic therapy for multiple myeloma and are within 2-12 months of the first dose of initial therapy. * At least 18 years of age. * ECOG performance status <= 2 * Normal bone marrow and organ function as defined below: * Platelets >= 50,000/mm3 * Hemoglobin >= 8.0 g/dL * Absolute neutrophil count >=1,000/mm3 * AST(SGOT)/ALT(SGPT) <= 3.0 x IULN * Total bilirubin <= 1.5 x IULN * Measured or calculated creatinine clearance >= 30 mL/min * Female patients who: * are postmenopausal for at least 1 year before the screening visit OR * are surgically sterile OR * Women of childbearing potential and men must agree to practice 2 effective methods of contraception prior to study entry, for the duration of study participation, and for 30 days after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. * Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable). Exclusion Criteria: * Previous stem cell collection or transplantation (autologous or allogeneic). * Evidence of multiple myeloma disease progression (as defined by IMWG) any time prior to auto-HSCT. * Diagnosis of plasma cell leukemia. * Concurrent hematologic or non-hematologic malignancy requiring treatment (other than multiple myeloma or secondary amyloidosis). * Radiation therapy within 3 weeks prior to enrollment. * Grade 2 or higher peripheral neuropathy. * Known hypersensitivity to any of the following: bortezomib, boron, mannitol. * Myocardial infarction within 6 months prior to enrollment or 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 * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, or serious medical or psychiatric illness/social situations that would limit compliance with study requirements. * Female patients who are pregnant and/or breastfeeding. Patient must have a negative serum pregnancy test within 14 days of study entry. * Known HIV-positivity. These patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients with HIV-positivity when indicated. * Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of the trial and throughout the duration of the trial

Study Objectives Primary Objectives: 1. To determine the efficacy of in vivo purging achieved by rituximab in the two groups. 2. To determine the number of apheresis procedures, total stem cell yield/kg patient body weight and the toxicity profile in the two groups. Secondary Objectives: 1. To determine the degree of expression of various adhesion molecules in the 2 groups and correlate with time to engraftment of neutrophils, platelets, and red blood cells, efficacy of stem cell mobilization and purging. 2. To determine the incidence of disease progression/relapse at 12 months in the two groups. Conditions: Lymphoma Intervention / Treatment: DRUG: Etoposide, DRUG: G-CSF, DRUG: GM-CSF, DRUG: Isophosphamide, DRUG: Rituximab, PROCEDURE: Apheresis Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patients with histologically confirmed CD20 positive B-cell non-Hodgkin's lymphoma who are candidates for autologous stem cell transplantation. * Age up to 70 years * Platelet count > 100,000 mm3, independent of transfusion support * Absolute neutrophil count (ANC) > 1500/mm3 * Zubrod performance status of 2 or less. * Negative pregnancy test in women * Less than 10% marrow involvement with lymphoma within 4 weeks of study enrollment as defined by bilateral bone marrow aspirations and biopsies. * Should be seronegative for HIV, HTLV, hepatitis B surface antigen, hepatitis C antibody. Exclusion Criteria: * Clinical or radiographic evidence of active CNS disease * Severe concomitant medical or psychiatric illness * Lactating or breast feeding females * Less than 3 weeks from the first day of last chemotherapy * Prior myeloablative therapy with autologous bone marrow or stem cell rescue * Serum bilirubin > 1.5 X ULN, Serum transaminases > 2XULN. * Serum creatinine >1.6 mg/dl * History of pelvic radiation * Patients should not have received more than 3 prior chemotherapy regimens (excluding radiation) * Patients should not have received more than 6 cycles of fludarabine therapy

Study Objectives This is a randomized, open-label, 2-arm, controlled, phase 2, multi-center, estimation clinical trial of docetaxel and cisplatin combination chemotherapy with and without panitumumab in the first-line treatment of subjects with metastatic or recurrent head and neck cancer, as well as a cross-over second-line panitumumab monotherapy of subjects who fail the chemotherapy only arm. This study will be conducted in the United States. Approximately 150 subjects with histologically or cytologically confirmed metastatic and/or recurrent SCCHN. Conditions: Metastatic or Recurrent Squamous Cell Carcinoma of Head and Neck Intervention / Treatment: DRUG: Cisplatin, DRUG: Panitumumab, DRUG: Docetaxel, DRUG: Cisplatin, DRUG: Docetaxel Location: Lithuania, Spain, United States, Belgium, Puerto Rico, Slovakia, Austria, Czechia, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed metastatic and/or recurrent Squamous Cell Carcinoma of Head and Neck (SCCHN) determined to be incurable by surgery and/or radiation therapy. * Measurable disease by CT scan * Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 * Age: >= 18 years * Adequate hematologic, renal, metabolic, hepatic & thyroid function Exclusion Criteria: * Prior systemic treatment for metastatic and/or recurrent SCCHN * CNS metastases, or nasopharyngeal carcinoma * History of interstitial lung disease * History of another primary cancer * Any co-morbid disease that would increase risk of toxicity * Active infection requiring systemic treatment * Prior anti-Epidermal Growth Factor receptor (anti-EGFr) antibody therapy

Study Objectives This phase II trial is studying how well sorafenib works in treating patients with unresectable or metastatic gallbladder cancer or cholangiocarcinoma. Sorafenib 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: Adenocarcinoma of the Extrahepatic Bile Duct, Adenocarcinoma of the Gallbladder, Adenocarcinoma With Squamous Metaplasia of the Gallbladder, Cholangiocarcinoma of the Extrahepatic Bile Duct, Cholangiocarcinoma of the Gallbladder, Recurrent Extrahepatic Bile Duct Cancer, Recurrent Gallbladder Cancer, Squamous Cell Carcinoma of the Gallbladder, Unresectable Extrahepatic Bile Duct Cancer, Unresectable Gallbladder Cancer Intervention / Treatment: DRUG: sorafenib tosylate, OTHER: laboratory biomarker analysis Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must have a cytologically or pathologically confirmed diagnosis of cholangiocarcinoma or gallbladder carcinoma * The pathologic confirmation of gallbladder or cholangiocarcinoma may be made from the primary or metastatic site; biopsy of the gallbladder or bile duct mass is not necessary; patients with pathologic confirmation of adenocarcinoma of a metastatic site, along with clinical documentation of gallbladder or bile duct involvement and no evidence of another primary are also eligible; if clinical documentation of gallbladder or bile duct involvement is not possible because of removal of the organ, a clinically and/or radiographically consistent picture plus pathologic findings from the metastatic site that are determined to be consistent with cholangiocarcinoma are acceptable * Eligible pathologic type: Patient must have one of the following subtypes: adenocarcinoma NOS, papillary carcinoma, adenocarcinoma, intestinal type, clear cell adenocarcinoma, mucinous adenocarcinoma, signet ring cell carcinoma, squamous cell carcinoma, adenosquamous carcinoma, small cell carcinoma, undifferentiated carcinoma, carcinoma NOS; patient must not have carcinoid tumors or sarcomas * Patient must have locally advanced or distant metastatic disease that is not surgically curable * Patient must have measurable disease; x-rays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration; x-rays, scans or other tests for assessment of non-measurable disease must have been performed within 42 days prior to registration; all disease must be assessed * Institutions are required to submit paraffin-embedded specimens * Institutions are required to seek additional patient consent for submission of blood * Patient may have had prior surgery, including surgery for their gallbladder or cholangiocarcinoma; patients must be at least 14 days beyond any major surgery, and recovered from all effects of surgery * Patient must not have received prior therapy for unresectable or metastatic disease; patient may have received prior chemotherapy, hormonal therapy, immunotherapy, radiation therapy (to less than 25% of bone marrow only) or chemoradiotherapy as neoadjuvant or adjuvant treatment; this must have been completed at least 12 months prior to documented recurrence or metastatic disease; patient must have recovered from all radiation induced toxicities * Prior radiation therapy to metastatic sites, such as bone, is allowed as long as the patient has measurable lesion(s) that were not treated with radiation therapy; at least 28 days must have elapsed since completion of radiation therapy, and patient must have recovered from all effects * Patient must not have received prior BAY 43-9006 or any inhibitor of VEGFR or the MAPK pathway * Patient must have Zubrod performance status of 0-1 * Total serum bilirubin =< 3 x the institutional upper limit of normal (IULN) * Serum transaminase (SGOT or SGPT) =< 2.5 x IULN; if liver metastasis is present, SGOT or SGPT must be =< 5 x IULN * Patients with biliary obstruction must have decompressions of the biliary tree by ERCP and stenting or percutaneous drainage * Serum creatinine =< 1.5 x IULN OR measured creatinine clearance >= 60 mL/min OR estimated creatinine clearance >= 60 mL/min * Leukocyte count >= 3,000/mcL * ANC >= 1,000/mcL * Platelets >= 100,000/mcL * PT, INR and PTT =< IULN * Patients must not be taking the cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, and Phenobarbital), rifampin, or St. Johns Wort * Patient must not be on therapeutic anticoagulation; prophylactic anticoagulation (i.e., low dose warfarin) of venous or arterial access devices is allowed provided that the requirements for PT, INR and PTT are met * Patient must not have any evidence of bleeding diathesis * Patients must not have clinically significant cardiac disease that is not well controlled by medication (e.g., congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias) or myocardial infarction within 12 months prior to registration * Patient must not have uncontrolled hypertension * Patient must not have known brain metastases because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events * Patient must either be able to swallow and/or receive enteral medications via gastrostomy feeding tube; tablets must not be crushed; patient must have the ability to absorb medication (i.e., no malabsorption syndrome); patient must not have intractable nausea or vomiting * Patient must have no plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy or any other type of therapy for treatment of cancer while on this protocol; radiation for palliation to metastatic sites is allowed as long gas the target lesions are not irradiated * Women/men of reproductive potential must agree to use an adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of protocol treatment; post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential; pregnant or nursing women are not eligible for this protocol; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; breastfeeding must be discontinued if the mother is treated with BAY 43-9006 * HIV-positive patients must have a CD4 count > 500 and must have no active opportunistic infection; in addition, patient must not be receiving combination anti-retroviral therapy * No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years * If day 14, 28 or 42 falls on a weekend or holiday, the limit may be extended to the next working day * In calculating days of tests and measurements, the day a test or measurement is done is considered day 0; therefore, if a test is done on a Monday, the Monday two weeks later would be considered day 14; this allows for efficient patient scheduling without exceeding the guidelines * All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines * At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base

Study Objectives This proposed study will examine feasibility and implement therapeutic bright light that is tailored to the individual's circadian typology to estimate its therapeutic effects on sleep/wake patterns and fatigue in breast cancer patients undergoing chemotherapy. Conditions: Breast Neoplasms, Breast Cancer, Cancer of Breast, Cancer of the Breast Intervention / Treatment: OTHER: Bright blue-green light using light visor cap, OTHER: Dim red light using light visor cap, OTHER: European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire, OTHER: Epworth Sleepiness Scale, OTHER: Pittsburgh Sleep Quality Index, OTHER: Patient-Reported Outcomes Measurement Information System (PROMIS)-Sleep Disturbance, OTHER: Patient-Reported Outcomes Measurement Information System (PROMIS)-Cancer-Fatigue, DIAGNOSTIC_TEST: Digital foot candle datalogging light meter (Extech Instrument, Model SDL400), DIAGNOSTIC_TEST: Polysomnography (Easy Ambulatory 2 Cadwell, Kennewick, WA), OTHER: Horne-Ostberg Morningness-Eveningness Questionnaire, OTHER: Daily Fatigue and Sleep Log Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * 21 years of age or older * Newly diagnosed with stage I-III breast cancer * Scheduled to receive 21-day cycles of intravenous chemotherapy * Experiencing disrupted sleep (determined by Pittsburgh Sleep Quality Index) * Morning or evening types (determined by Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ) * Sighted * Mentally competent to consent * Able to under English Exclusion Criteria: * Concurrent malignancy * Undergoing other cancer treatments * Engage in shift work or travel across more than 3 time zones within 2 weeks prior to study * Known history of seasonal affective disorder or substance abuse * Current diagnosis of major Axis I psychiatric disorders, neurological impairments, or muscular dystrophies * Regularly use steroid or other immunosuppressive medications * Take prescribed sedative hypnotics or sleep medications because these conditions may affect fatigue and/or sleep/wake patterns. * Have eye conditions (glaucoma or retinal disease), problems triggered by bright light (e.g. migraine), or take photosensitizing medications (e.g. some porphyrin drugs, antipsychotics, antiarrhythmic agents)

Study Objectives The primary objective of this study is to demonstrate an improvement in Progression-Free Survival (PFS) for the combination of vandetanib plus gemcitabine compared with gemcitabine plus placebo in chemonaïve (not including an adjuvant regimen) patients aged ≥ 70 years with advanced NSCLC. Conditions: Non Small Cell Lung Cancer Intervention / Treatment: DRUG: ZD6474, Vandetanib, DRUG: Placebo to Match ZD6474, Vandetanib, DRUG: Gemcitabine Location: Italy Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * Histologic or cytologic confirmation of advanced NSCLC (stage IIIB with supraclavicular lymph node metastases or pleural effusion or stage IV) on entry into study * One or more measurable lesions at least 10 mm in the longest diameter (LD) by spiral CT scan or 20 mm with conventional techniques according to RECIST criteria * Chemotherapy-naïve (prior chemotherapy in the adjuvant setting completed more than 3 months before the trial entry is accepted). * Female or male aged 70 years or above Exclusion Criteria: * Patients must not have received prior anti-cancer therapy except in the adjuvant setting * Inadequate end-organ function or Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the trial * Significant cardiovascular event (e.g. myocardial infarction, superior vena cava [SVC] syndrome, New York Heart Association [NYHA] classification of heart disease ³2) within 3 months before entry, or presence of cardiac disease that in the opinion of * History of arrhythmia or QTc with Bazett's correction unmeasurable or >= 480 msec on screening ECG

Study Objectives The purpose of this study is to test the safety of RAD001 (everolimus) tablets at different dose levels, when added to docetaxel and cisplatin. The investigators want to find out what effects, good and/or bad, that everolimus has when added to docetaxel and cisplatin as treatment for head and neck cancer. Conditions: HEAD & NECK Cancer Intervention / Treatment: DRUG: RAD001 + docetaxel + cisplatin 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: * Stage III-IVB head and neck squamous cell carcinoma (HNSCC) or nasopharyngeal cancer (WHO type I, II or III),, previously untreated. Patients with stage II hypopharynx HNSCC will also be eligible. Pathology must be confirmed at MSKCC * Age >= 18 years * Karnofsky performance status >= 70% * Adequate bone marrow function: Absolute neutrophil count >= 1.5 X 109/L, Platelets >= 100 x 109/L, Hemoglobin > 10 g/dL. * Adequate liver function Serum bilirubin must be within the upper limit of normal. (ULN). AST and ALT and Alkaline Phosphatase must be within the range allowing for eligibility * Adequate renal function: serum creatinine within institutional normal limits, or calculated creatinine clearance (by Cockcroft and Gault method) >= 55 mL/min for patients with creatinine limits above institutional normal * INR < 1.5 or aPTT < 1.5 X upper limits of normal * Negative urine or serum pregnancy test within 14 days prior to administration of RAD001 * Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter. * Patients must have ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * Any prior treatment with RAD001, or other agents specifically targeting mTOR * Any prior radiation therapy for head and neck cancer. Any prior radiation therapy to >25% of the bone marrow. Any prior radiation to whole pelvis and/or brain * Therapeutic anticoagulation with coumadin (warfarin) * Hypertriglyceridemia >= grade 2 (CTCAE version 3.0) * Patients who require chronic treatment with steroids ( > prednisone 5 mg/day) or other immunosuppressive agents are excluded. Both cisplatin and RAD001 are immunosuppressive, and chronic steroid use (> prednisone 5 mg/day) or use of other immunosuppressive agents might increase the risk of lethal infection in this setting. Patients on low- dose steroid replacement regimens (<= prednisone 5 mg/day) are not excluded, because low dose steroids should not be immunosuppressive * Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) * Active infection or serious underlying medical condition that would impair the patient's ability to receive protocol treatment. Other concurrent severe and/or uncontrolled medical disease which would compromise participation in the study in the opinion of the investigator (e.g., uncontrolled diabetes, unstable angina, or congestive heart failure - New York Heart Association Class III or IV) * HIV-positive patients. These patients are at increased risk of lethal infections when treated with marrow suppressive therapy. Additionally, pharmacokinetic interactions between antiretroviral therapy and the study regimen may be problematic for these patients * Women who are pregnant or lactating * Other active malignancy, other than indolent malignancies which the investigator determines are unlikely to interfere with treatment and safety analysis. For example, patients with non-melanoma skin cancer, in situ carcinoma of the cervix, or prostate cancer with no current biochemical (PSA) or radiologic evidence of disease may enroll * Patients with hearing loss requiring hearing aid or intervention (i.e. interfering in a clinical significant way with activities of daily living). * Patients with multifocal peripheral sensory alterations or paresthesias (including tingling) interfering with function, per patient report (example: activities of daily living) * Impaired lung function: O2 saturation 88% or less at rest on room air by Pulse Oximetry. If O2 saturation is <= 88% at rest, further pulmonary function tests (PFTs) should be ordered to confirm normal pulmonary function and eligibility * Patients should not receive immunization with attenuated live vaccines within one week of study entry or during the study period. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines * Liver disease such as cirrhosis or severe hepatic impairment (Childs-Pugh class C)

Study Objectives This randomized phase II trial is studying three different schedules of gemcitabine hydrochloride and tanespimycin to see how well they work in treating patients with stage IV pancreatic cancer. Drugs used in chemotherapy, such as gemcitabine hydrochloride and tanespimycin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells Conditions: Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage IV Pancreatic Cancer Intervention / Treatment: DRUG: gemcitabine hydrochloride, DRUG: tanespimycin Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed pancreatic adenocarcinoma * Clinical stage IV disease * No known brain metastases * ECOG performance status 0-2 * Life expectancy >= 12 weeks * Absolute Neutrophil Count (ANC) >= 1,500/mm³ * Platelet count >= 100,000/mm³ * Total bilirubin normal * Aspartate aminotransferase (AST) <= 2.5 times upper limit of normal (ULN) * Alkaline phosphatase <= 2 times ULN (5 times ULN if liver metastases are present) * Creatinine normal * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Ejection fraction > 40% by echocardiogram * Patients who received prior anthracyclines must have a normal ejection fraction by echocardiogram * Corrected QT interval (QTc) < 500 msec * Pulse oximetry > 88% on room air at rest and after gentle exercise (according to Group Medicare Guidelines) * No history of allergic reactions attributed to compounds of similar chemical or biologic composition to tanespimycin (17-AAG) or gemcitabine hydrochloride * No known allergy to eggs * No concurrent uncontrolled illness including, but not limited to, any of the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness/social situations that would limit compliance with study requirements * No active ischemic heart disease within the past 12 months * No history of uncontrolled dysrhythmias * No congenital long QT syndrome * No left bundle branch block * No other significant cardiac disease, including any of the following: * New York Heart Association class III or IV heart failure * Myocardial infarction within the past year * Poorly controlled angina * Uncontrolled dysrhythmias * History of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation >= 3 beats in a row) * No clinically significant interstitial lung disease * No symptomatic pulmonary disease requiring medication, including any of the following: * Dyspnea * Dyspnea on exertion * Paroxysmal nocturnal dyspnea * Significant pulmonary disease requiring oxygen*, including chronic obstructive/restrictive pulmonary disease * No pulmonary or cardiac symptoms >= grade 2 * No history of cardiac or pulmonary toxicity after receiving anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or vincristine) * No prior chemotherapy for metastatic disease * No prior radiotherapy to the chest * No prior radiotherapy that potentially included the heart in the field (e.g.,mantle radiotherapy) * More than 3 months since prior adjuvant chemotherapy or chemotherapy for locally advanced disease * More than 3 weeks since prior radiotherapy * No concurrent medications that prolong or may prolong QTc * No concurrent antiarrhythmic drugs * No concurrent prophylactic colony-stimulating factors * No other concurrent investigational agents * No other concurrent anticancer therapy

Study Objectives The purpose of this study is to evaluate the safety and tolerability of romiplostim in thrombocytopenic patients with low or Intermediate-1 risk MDS. In addition, the study will evaluate the platelet response to romiplostim. Conditions: Thrombocytopenia, MDS, Myelodysplastic Syndromes, Refractory Cytopenias Intervention / Treatment: DRUG: Romiplostim Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Diagnosis of MDS using the World Health Organization classification * Low or Intermediate-1 risk MDS using the International Prognostic Scoring System (IPSS) * The mean of two platelet counts taken during the screening period must be <= 50 x 10^9/L, with no individual count > 55 x 10^9/L (The mean platelet counts of 5 subjects enrolled at the maximum tolerated dose (MTD) must be <= 20 x 10^9/L). Standard of care platelet assessments taken prior to Informed Consent may be used as 1 of the 2 counts taken within 3 weeks prior to study day 1. * Must be >= 18 years of age at the time of obtaining informed consent * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of screening * Adequate Liver Function, as evidenced by a serum bilirubin <= 1.5 times the laboratory normal range (except for patients with a confirmed diagnosis of Gilbert's Disease), alanine aminotransferase (ALT) <= 3 times the laboratory normal range, and aspartate aminotransferase (AST) <= 3 times the laboratory normal range * A serum creatinine concentration <= 2 mg/dL (<= 176.6 µmol/L) * Before any study-specific procedure, the appropriate written informed consent must be obtained (see Section 12.1) Exclusion Criteria: * Currently receiving any treatment for MDS other than transfusions and erythropoietic growth factors. If granulocyte growth factors are currently being received, they cannot be used on or after study day 1 * Clinically significant bleeding within 2 weeks prior to screening (eg, gastrointestinal (GI) bleeds, intracranial hemorrhage) * Prior malignancy (other than controlled prostate cancer, in situ cervical cancer or basal cell cancer of the skin) unless treated with curative intent and without evidence of disease for >= 3 years before screening * Prior history of bone marrow transplantation * Persistent peripheral blood monocytosis (>= 3 months with an absolute monocyte count > 1,000/µL) * Unstable angina, congestive heart failure (New York Heart Association [NYHA] > class II), uncontrolled hypertension (diastolic > 100 mmHg), uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction * Received Anti-Thymocyte Globuline (ATG) within 6 months of screening * Received hypomethylating agents, immunomodulating agents, histone deacetylase inhibitors, cyclosporine or mycophenolate within 6 weeks of screening * Received interleukin (IL)-11 (oprelvekin) within 4 weeks before screening * Concurrent use of granulocyte growth factors (i.e. granulocyte-colony stimulating factor [G-CSF; Neupogen, Granocyte], pegfilgrastim [Neulasta], granulocyte macrophage-colony stimulating factor [GM-CSF; Leukine, Prokine, Sargramostim]) * Have ever previously received recombinant thrombopoietin (rTPO), pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), eltrombopag, or romiplostim * Less than 4 weeks since receipt of any therapeutic drug or device that is not Food and Drug Administration (FDA) approved for any indication * Other investigational procedures are excluded * History of arterial thrombosis (eg, stroke or transient ischemic attack) in the past year * History of venous thrombosis that currently requires anti-coagulation therapy * Untreated B12 or folate deficiency * Subject is evidently pregnant (eg, positive human chorionic gonadotropin [HCG] test) or is breast feeding * Subject is not using adequate contraceptive precautions * Subject has known hypersensitivity to any recombinant E coli-derived product * Subject previously has enrolled in this study * Subject will not be available for follow-up assessment * Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures

Study Objectives The goal of this clinical research study is to learn if giving busulfan in a dose based on blood levels, along with a fixed (unchanging) dose of fludarabine, is more effective and causes fewer side effects for AML or myelodysplastic syndrome patients than the standard method of giving a fixed busulfan dose based on body size, along with a fixed dose of fludarabine. The safety of dosing based on blood levels will also be studied. Conditions: Myelodysplastic Syndrome, Leukemia, Acute Myeloid Leukemia Intervention / Treatment: DRUG: Busulfan, DRUG: Fludarabine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Acute myeloid leukemia past first remission, in first or subsequent relapse, in first remission (cytogenetics other than t(8;21, inv 16, t(15;17)) or induction failures. Only myeloid leukemia but not biphenotypic leukemia is allowed on this study. * Myelodysplastic syndromes with intermediate or high risk International Prognostic Scoring System score * Patient has not been administered any other systemic chemotherapeutic drug (including Mylotarg) within 21 days prior to trial enrollment (BMT Day -7 or day -9 for the test-dose arm of the study). Hydroxyurea is permitted if indicated to control induction refractory disease, and IT chemotherapy is allowed if indicated as maintenance treatment for previously diagnosed leptomeningeal disease, that has been in remission for at least 3 months prior to enrollment on this study). * No active infection. Protocol PI will be final arbiter if there is uncertainty regarding whether a previous infection is resolved. * age <=65 * Patients must have a matched related or unrelated donor willing to donate. A donor who is HLA identical or mismatched in 1 locus on Class I [HLA, A or B], or molecularly mismatched in 1 locus on Class II [HLA, DR or DQ] is also acceptable. * ZUBROD performance status <2 * Life expectancy is not severely limited by concomitant illness and expected to be >12 weeks. * Left ventricular ejection fraction >45% No uncontrolled arrhythmias or symptomatic cardiac disease. * No symptomatic pulmonary disease. Forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusion capacity of lung for carbon monoxide (DLCO) >= 50% of expected corrected for hemoglobin. In patients <= 7 years pulmonary function will be assessed per pediatric BMT routine * Serum creatinine <= 1.5 mg%. * Serum glutamate pyruvate transaminase (SGPT) <= 200 IU/ml, serum bilirubin and alkaline phosphatase within accepted laboratory standard normal limits or considered not clinically significant. No evidence of chronic active hepatitis or cirrhosis. If positive hepatitis serology, discuss with Study Chairman and consider liver biopsy. * No effusion or ascites >1L prior to drainage. * HIV-negative. * Female patient is not pregnant (negative B-human chorionic gonadotropin (HCG) pregnancy test in all women of child-bearing-potential in accordance with departmental routine). * Patient or patient's legal representative, parent(s) or guardian able to sign informed consent. * No prior autologous stem cell transplants Exclusion Criteria: 1) None.