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Study Objectives The beneficial of perioperative usage of thoracic epidural anesthesia and analgesia in various thoracic and upper abdominal surgery are well studied. However, intraoperative data are lacking whether combined thoracic epidural and general anesthesia have effect on the median (50%) effective effect-concentration (EC50) of propofol for inducing loss of consciousness (LOC). We performed this study among patients undergoing open gastrectomy in gastric cancer patients. Sixty patients undergoing open gastrectomy were randomly assigned to two groups with thoracic combined general anesthesia (TEA+GA) or general anesthesia (GA) alone. Target-controlled infusion (TCI) of propofol was used for anesthesia induction. The initial propofol concentration of target effect-site (Ceprop) was 3.5 ug/ml and was increased stepwise by 0.5ug/ml at each 4 min intervals by an un-down sequential method to reach LOC. The predicted Ceprop at the time of LOC, intravenous anesthetics, vasopressor requirement, emergency time from anesthesia and postoperative numeric rating scale (NRS) were recorded and analyzed between two groups. Conditions: Gastric Cancer Intervention / Treatment: DRUG: 5-8ml 0.375% ropivacaine, OTHER: 5-8ml normal saline Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: SINGLE_GROUP Masking: DOUBLE

Inclusion Criteria: Gastric cancer patients age between 18-75 yrs; ASA physical state I and II Undergoing open gastrectomy Exclusion Criteria: With contraindications to epidural puncture or catheter placement Chronic or acute (within 48 h) intake of psychotropic drugs, benzodiazepines, anticonvulsants, or opioids; alcoholism Hepatic, renal, neurological or other organ dysfunctiony Younger than >= 18 years than 75 years Allergic to local anesthetic solutions or opioids Received neo-adjuvant chemotherapy Refuse to receive epidural puncture

Study Objectives This study aims to determine Oncostatin M (OSM), Leukemia inhibitory factor (LIF), and Interleukin-11 (IL-11) levels in gingival crevicular fluid (GCF), saliva, and serum in periodontally healthy individuals and those with gingivitis and chronic periodontitis before and after periodontal treatment and to evaluate the relationship between these cytokine levels and clinical periodontal parameters. Conditions: Chronic Periodontitis, Generalized, Gingivitis Intervention / Treatment: PROCEDURE: Initial Periodontal Therapy Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SCREENING Allocation: NON_RANDOMIZED Interventional Model: FACTORIAL Masking: NONE

Inclusion Criteria: * systemically healthy * non-smokers Exclusion Criteria: * smokers * pregnancy or lactation * individuals with any systemic disease * individuals who have had periodontal treatment in the last six months

Study Objectives This study investigates the effect of acupuncture in reducing symptom distress in adults with advanced colon cancer. Conditions: Colorectal Neoplasms Intervention / Treatment: PROCEDURE: Acupuncture Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: SINGLE_GROUP Masking: SINGLE

Inclusion criteria: * Advanced colon cancer that has not responded to two rounds of chemotherapy * Speak, read, write English * Live within a 50 mile radius of Pittsburgh, PA * Not taking any steroid medication * A platelet count of 75,000 or greater * Never had acupuncture before Exclusion Criteria: * Allergy to stainless steal * Implanted pacemaker * Current skin infection * Needle phobia * Metastatic disease to the central nervous system (brain, spinal cord)

Study Objectives The purpose of this study is to examine the efficacy of Bevacizumab in addition to platinum-based chemotherapy for first-line treatment of participants with advanced stage (IIIB/IV) non-small cell lung cancer (NSCLC) other than predominantly squamous cell histology. Conditions: Carcinoma, Non-Small-Cell Lung Intervention / Treatment: DRUG: Bevacizumab Location: Hungary Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: In accordance with the SPC. Most important criteria: * Histology or cytology proven inoperable, locally advanced,metastatic or recurrent (stage IIIB/IV) NSCLC other than predominantly squamous cell histology * First-line treatment is indicated * No previous treatment with Bevacizumab Exclusion Criteria: In accordance with the SPC. Most important criteria: * Hypersensitivity to the active ingredient or to any of the excipients * Hypersensitivity to products derived from Chinese hamster ovary (CHO) cells or to other recombinant human or humanized antibodies * Pregnancy * Bevacizumab is contraindicated in the presence of untreated central nervous system metastases

Study Objectives Ewing Sarcoma Primary objectives: Standard Risk R1: in a randomised trial, to examine whether add-on treatment with zoledronic acid in addition to induction and maintenance chemotherapy improves event-free survival in patients with localised Ewing sarcoma and good histological response or with initial tumour volume \<200 mL compared to no add-on treatment. \*High Risk R2: in a randomised trial, to examine whether high-dose chemotherapy using busulfan-melphalan with autologous stem cell reinfusion, compared with standard chemotherapy, improves event-free survival in patients with localised Ewing sarcoma and poor histological response or tumour volume ≥200 mL (R2loc). In patients with pulmonary metastases high dose busulfan-melphalan chemotherapy with autologous stem cell reinfusion is randomised versus standard chemotherapy plus whole lung irradiation (R2pulm). Very High Risk R3: in a randomised trial, to examine whether the addition of high dose chemotherapy using treosulfan-melphalan followed by autologous stem cell reinfusion to eight cycles of standard adjuvant chemotherapy, compared to eight cycles of standard adjuvant chemotherapy alone, improves event-free survival in patients with primary disseminated disease. \*R2 accrual discontinued on December 1st 2015. Conditions: Ewing's Sarcoma Intervention / Treatment: DRUG: Zoledronic acid, DRUG: Busulfan, DRUG: Treosulfan Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Diagnosis: Histologically confirmed Ewing sarcoma of bone or soft tissue. * Age and sex: Either sex, age >48 months (for GPOH patients) and <50 years at the date of diagnostic biopsy. Younger or elderly patients may be reported to the appropriate office (see section 1.4) but are not included in this study. * Registration: <= 45 days after diagnostic biopsy/surgery. * Start of chemotherapy: <= 45 days after diagnostic biopsy/surgery. * Informed consent: Must be signed prior to study entry. * Performance status: Lansky or Karnofsky score > 50%, may be modified for handicapped patients. * Haematological parameters: * Haemoglobin > 8 g/dl (transfusion allowed), * Platelets > 80.000/µl (transfusion allowed), * WBC > 2000/µl. * Cardiac values: LVEF > 40%, SF > 28%. Exclusion Criteria: * More than one cycle of other chemotherapy prior to registration * Second malignancy * Pregnancy and lactation * Concurrent treatment within any other clinical trial, except trials with different endpoints that due to the nature of their endpoints must run parallel to EWING 2008 e.g. trials on antiemetics, antimycotics, antibiotics, strategies for psychosocial support, etc... * Any other medical, psychiatric, or social condition incompatible with protocol treatment

Study Objectives The purpose of this study is to assess the efficacy and safety of oral propranolol versus nadolol in patients with Infantile Hemangiomas (IH) in a randomized, controlled, double-blinded study. Conditions: Infantile Hemangioma Intervention / Treatment: DRUG: Nadolol, DRUG: Propranolol Location: Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * 1-6 months corrected age * Written parental informed consent * At least one of the following: * Size: hemangioma >1.5 cm on the face or >3 cm on other body parts * Causing or with potential for functional impairment (e.g. amblyogenic IH, ulcerated hemangioma) * Causing or with potential for cosmetic disfigurement (e.g. nasal tip, glabella location) Exclusion Criteria: * Contraindications to beta-blockers * Hypotension * Bradycardia * Hypoglycemia * Cardiac disease associated with decreased ejection fraction and/or > second degree heart block * Bronchospasm (including bronchial asthma) * Allergic rhinitis * Corrected gestational age less than 1 month at screening * Patients with PHACES cerebral arteriopathy at risk of stroke * Patients and/or breastfeeding mothers receiving treatment with anti-arrhythmic agents, calcium channel blockers, ACE inhibitors, inotropic agents, vasodilators, hypoglycemic agents, neuroleptics, antiacids, benzodiazepines, thyroxine, warfarin * Patients treated with an oral beta-blocker or other agent (e.g. systemic steroids, vincristine) within 2 weeks from randomization * Patients treated with topical timolol within 1 week from randomization * Vascular tumors other than infantile hemangioma (e.g. pyogenic granuloma, hemangioendothelioma)

Study Objectives The purpose of this study is to evaluate the tolerability and safety of Daratumumab in Japanese participants with relapsed (the return of a medical problem) or refractory (not responding to treatment) multiple myeloma (cancer of plasma cells in bone marrow, characterized by the presence of abnormal proteins in the blood). Conditions: Multiple Myeloma Intervention / Treatment: DRUG: Daratumumab Location: Japan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Participants proven to have symptomatic (having symptoms) multiple myeloma according the International Myeloma Working Group (IMWG) diagnostic criteria * Participant must have measurable disease defined by either or both the following measurements: a) Serum M-protein greater than or equal to (>=) 1 gram per deciliter (g/dL) (>=10 gram per liter [g/L]) (except for serum immunoglobulin A [IgA] M-protein >= 0.5 g/dL); b) Urine M-protein >=200 milligram per 24 hour (mg/24 h); in case immunoglobulin D [IgD] or immunoglobulin E [IgE] M-protein, quantification should be performed * Participant must have relapsed or refractory multiple myeloma after receiving at least 2 previous therapies, and without further established treatment options * Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 * Participant must have life expectancy greater than (>) 3 months Exclusion Criteria: * Participant has received daratumumab or other anti-cluster of differentiation 38 (anti-CD38) therapies previously * Participant has received anti-myeloma treatment within 2 weeks before administration of the study drug * Participant has previously received an allogenic stem cell transplant; or participant has received autologous stem cell transplantation (ASCT) within 12 weeks before administration of the study drug * Participant has a history of malignancy (other than multiple myeloma) within 5 years before administration of the study drug * Participant is exhibiting clinical signs of meningeal involvement of multiple myeloma

Study Objectives This phase II trial is studying the side effects and how well ixabepilone works in treating patients with persistent or recurrent uterine cancer. Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells of by stopping them from dividing. Conditions: Recurrent Uterine Corpus Sarcoma, Uterine Carcinosarcoma Intervention / Treatment: DRUG: Ixabepilone, 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 histologically confirmed uterine carcinosarcoma which is persistent or recurrent with documented disease progression after appropriate local therapy; acceptable histologic type is defined as carcinosarcoma (malignant mixed muellerian tumor), homologous or heterologous type * All patients must have measurable disease; measurable disease is defined by Response Evaluation Criteria In Solid Tumors (RECIST) (version 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 >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI * Patients must have at least one ?target lesion? to be used to assess response on this protocol as defined by RECIST version 1.1; 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 * Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG Phase III or Rare Tumor protocol for the same patient population * Patients must have a GOG Performance Status of 0, 1, or 2 * Recovery from effects of recent surgery, radiotherapy, or chemotherapy * Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI]) * Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration * Any other prior therapy directed at the malignant tumor, including biological and immunologic agents, must be discontinued at least three weeks prior to registration * Patients must have had one prior chemotherapeutic regimen for management of carcinosarcoma; initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen * Patients who have NOT received prior therapy with a taxane (such as paclitaxel or docetaxel) MUST receive a second regimen that includes a taxane * Patients must have NOT received any additional cytotoxic chemotherapy except as noted above * Patients are allowed to receive, but are not required to receive, one additional non-cytotoxic regimen for management of recurrent or persistent disease according to the following definition: * Non-cytotoxic (biologic or cytostatic) agents include (but are not limited to) monoclonal antibodies, cytokines, and small-molecule inhibitors of signal transduction * Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl * Platelets greater than or equal to 100,000/mcl * Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN) * Bilirubin less than or equal to 1.5 x ULN * Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) less than or equal to 3 x ULN * Alkaline phosphatase less than or equal to 2.5 x ULN * Patients must have signed an approved informed consent and authorization permitting release of personal health information Exclusion Criteria: * Neuropathy (sensory and motor) less than or equal to grade 1 * Patients who have met the pre-entry requirements * Patients of childbearing potential must have a negative serum pregnancy test 72 hours prior to the study entry and be practicing an effective form of contraception * Patients who have received prior therapy with Ixabepilone * Patients with a known history of severe (Common Terminology Criteria for Adverse Events [CTCAE] version [v]4.0) grade 3 or 4 hypersensitivity reaction to agents containing Cremophor? EL or its derivatives (eg, polyoxyethylated castor oil) * Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, and other specific malignancies, are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy * Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of uterine carcinosarcoma within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease * Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of uterine carcinosarcoma within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease * Patients who are pregnant or nursing

Study Objectives This is a randomized, international, multicenter, Phase II study designed to explore the efficacy of olaparib or olaparib in combination with durvalumab in platinum-treated mTNBC. The primary objectives are to explore olaparib or olaparib in combination with durvalumab as maintenance therapy following clinical benefit with platinum-based therapy in subjects with mTNBC. Conditions: Triple Negative Breast Cancer Intervention / Treatment: DRUG: Olaparib Oral Product, DRUG: Olaparib Oral Product in combination with Durvalumab Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Age >= 21 years of age * ECOG performance status 0-2 * Inoperable locally advanced or metastatic breast cancer not amenable to resection with curative intent and histologically confirmed to be estrogen receptor (ER) negative, progesterone receptor (PR) negative, and HER2 negative: * ER negative status is defined as < 1% tumor cells positive for ER by immunohistochemistry (IHC), irrespective of staining intensity * PR negative status is defined as < 1% tumor cells positive for PR by IHC, irrespective of staining intensity NOTE: Enrollment is permitted for ER/PR low-expression subjects (defined as <= 10%) who are expected to benefit from this trial at the investigator's discretion. * HER2 negative status is determined by: * IHC 1+, as defined by incomplete membrane staining that is faint/barely perceptible and within > 10% of invasive tumor cells, or * IHC 0, as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within <= 10% of the invasive tumor cells, or * FISH negative based on: * Single-probe average HER2 copy number < 4.0 signals / cell, or * Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number < 4.0 signals / cell * Minimum six 1-weekly doses or three 3-weekly doses of platinum chemotherapy (monotherapy or combination therapy at investigator's discretion) with stable disease (SD), partial response (PR) or complete response (CR) to the platinum therapy as assessed by investigator. * Has received no more than 2 prior chemotherapy regimens for metastatic breast cancer including current platinum based chemotherapy. * Able to provide a representative formalin-fixed, paraffin embedded tumour specimen archival or fresh tissue for correlative studies and biomarker analysis. * Hemoglobin >= 9.0 g/dL and no blood transfusions in the 28 days prior to study entry. Absolute neutrophil count >=1,500/mm3. Platelet count >=100 x 10^9/L. * Total bilirubin <1.5 x the upper limit of normal (ULN) with the following exception: subjects with known Gilbert's disease who have serum bilirubin <3 x ULN may be enrolled. * Aspartate transaminase (AST) and alanine transaminase (ALT) <2.5 x ULN with the following exceptions: subjects with documented liver or bone metastases may have AST and ALT <5 x ULN. * Alkaline phosphatase (ALP) <2 x ULN (<5 x ULN in subjects with known liver involvement and <7 ULN in subjects with known bone involvement). * Serum creatinine <1.5 x ULN or creatinine clearance >51 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance. * For subjects of childbearing potential, agreement (by both subject and partner) to use two effective forms of contraception, including surgical sterilization, reliable barrier method, birth control pills, contraceptive hormone implants, or true abstinence and to continue its use for the duration of the study and for 3 months after last dose of study treatment. * Subjects of childbearing potential should have a negative urine or serum pregnancy test during their screening visit. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. * Subjects willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examination. * For inclusion in genetic research, subjects must provide informed consent for genetic research collection of specimens to be stored at repository for future research. Exclusion Criteria: * Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of first dose of treatment. Subjects who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks since last dose of the previous investigational agent or device. * Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study. * Active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, or similar treatment) is not considered a form of systemic treatment. * Is taking chronic systemic steroids in doses > 10mg of prednisolone or equivalent within 7 days prior to the first dose of trial treatment. * Previous treatment with PARP inhibitors including olaparib. * Patients that have required discontinuation of treatment due to treatment-related toxicities from prior therapy with PD-1, PDL-1 or CTLA-4 inhibitors or previous history of immune-related grade 3 or 4 adverse event. * Known active central nervous system metastasis and / or carcinomatous meningitis. Subjects with previously treated brain metastases may participate, provided they have: 1. Stable brain metastases [without evidence of progression by imaging (confirmed by computerized tomography {CT} scan if CT used at prior imaging) for at least four weeks prior to the first dose of trial treatment**, 2. No evidence of new or enlarging brain metastases; any neurologic symptoms should have returned to baseline, 3. Not used steroids for brain metastases in the 7 days prior to trial initiation. Taking chronic systemic steroids in doses <= 10mg of prednisolone is allowed. * This exception does not include carcinomatous meningitis, as subjects with carcinomatous meningitis are excluded regardless of clinical stability. * History and/or confirmed pneumonitis, or extensive bilateral lung disease on high resolution/spiral CT scan. * Patients with suspected or confirmed myelodysplastic syndrome/acute myeloid leukemia. * History of another primary malignancy except for: 1. Malignancy treated with curative intent and with no known active disease >=5 years before the first dose of study drug and of low potential risk for recurrence. 2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. 3. Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ. * Major surgery within 2 weeks of starting the study, and subjects must have recovered from any effects of any major surgery. * Receipt of radiation therapy within 4 weeks prior to starting study drug(s). Limited field of radiation for palliation within 2 weeks of the first dose of study treatment is allowed provided: 1. The lung is not in the radiation field 2. Irradiated lesion(s) cannot be used as target lesions * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease, active bleeding diatheses including any subjects known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness / social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent. * Subjects unable to swallow orally administered medication, and subjects with gastrointestinal disorders likely to interfere with absorption of the study medication. * Subjects requiring treatment with potent inhibitors or inducers of CYP3A4. * Pregnant or breast-feeding women. If breastfeeding can be stopped prior to study enrollment until 1 month after the last study dose, then the patient could be allowed to enter the study. * Immunodeficient subjects, eg, subjects who are known to be serologically positive for human immunodeficiency virus (HIV). * Received a live vaccine within 30 days of planned start of study therapy. * Subjects with a known hypersensitivity to olaparib or durvalumab, or any of the excipients of the product. * Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis) * History of allogeneic organ transplant * Active bleeding diatheses * Patients with known active hepatic disease (ie, Hepatitis B or C) * Known history of previous clinical diagnosis of tuberculosis.

Study Objectives To study the efficacy of Alimta as a single agent in thymic cancers Conditions: Thymoma, Thymic Carcinoma Intervention / Treatment: DRUG: Premetrexed (Alimta) Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed invasive, recurrent or metastatic thymoma or thymic carcinoma not amenable to potentially curative therapy by surgery. Original biopsy of tumor is sufficient for diagnoses unless otherwise clinically indicated. * Patients must have measurable disease with at least one bidimensional measurable lesion. Any scans or x-rays used to document measurable disease must be obtained with 6 weeks prior to registration. * Patients may have had prior chemotherapy for metastatic disease * Adequate organ function as defined by: bili <=1.5; calc. crt clr of >=45; hematologic-granulocytes >=1500 & plt >=100K. * Patients who are receiving a stable dose of corticosteroids for myasthenia gravis are eligible. * ECOG performance status of 0 or 1 Exclusion Criteria: * Acute intercurrent infection or complications * pregnancy or lactating patients * Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents for a 5-day period (8-day period for long-acting agents. * Presence of clinically relevant third-space fluid collections that cannot be controlled by a procedure

Study Objectives Primary Objective: - To assess the effect of SAR302503 (500 mg) administered as 14-day repeated doses on the QTcF interval compared to 1-day placebo in patients with advanced solid tumors. Secondary Objectives: * To assess the effect of SAR302503 administered as 14-day repeated doses on heart rate (HR), QT, QTcB, and QTcN, PR and QRS compared to placebo. * To assess the clinical and laboratory safety of SAR302503 * To document the plasma concentrations of SAR302503 at the time of ECG investigation. * To explore the Pharmacokinetic/Pharmacodynamic relationship between SAR302503 concentration and QTcF * To explore antitumor activity Conditions: Neoplasm Malignant Intervention / Treatment: DRUG: SAR302503 (TG101348), DRUG: Placebo SAR302503, DRUG: Panolosetron Location: United States, Belgium Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: BASIC_SCIENCE Allocation: NON_RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion criteria : * Histologically or cytologically confirmed advanced solid malignancy that is metastatic or unresectable, and for which standard curative measures do not exist Exclusion criteria: * Prior history of torsades de pointe, or congenital long QT syndrome. * Conditions with screening ECG in which repolarization is difficult to interpret, or showing significant abnormalities. This includes, but is not limited to: High degree atrioventricular (AV) block, pacemaker, atrial fibrillation or flutter * Screening ECG with QTc B or QTc F >=480 msec (within 8 days of Day-1) * Significant hypokalemia at screening (K+ <3.5 mmol/L) (within 8 days of Day-1) * Significant hypomagnesemia at screening and inclusion (Mg++ <0.7 mmol/L) (within 8 days of Day -1) * Patient receives (and cannot discontinue), or is scheduled to receive, a concomitant treatment known to carry a risk of both QT prolongation and torsade de pointe for 2 weeks before Day 1 and for the duration of Segment 1 * Absence of completion of all prior chemotherapy, biological therapy, hormonal therapy, targeted non-cytotoxic therapy >=3 weeks; and radiotherapy >=2 weeks prior to inclusion. * Patients with uncontrolled brain metastases or primary brain tumor. Patients with brain metastasis are considered eligible if the patient has not received radiation therapy for brain metastasis within 2 weeks of enrollment and has been on a stable dose of steroids for >= 2 weeks. * Participation in any study of an investigational agent (drug, biologic, device) within 30 days prior to initiation of study drug, unless during non-treatment phase. * Anticipation of need for a major surgical procedure or radiation therapy during the study treatment. * Concurrent treatment in another clinical trial or with any other cancer therapy including chemotherapy, biological therapy, hormonal therapy, radiotherapy, chemoembolization, cryotherapy, targeted non-cytotoxic therapy or patients planning to receive these treatments during the study. * Inadequate organ function as defined by: * Absolute neutrophil count (ANC) <1.5 X 10^9/L * Platelet count <100 X 10^9/L * Hemoglobin: <9 g/dL * Serum creatinine >1.5 x the upper limit of normal (ULN) * Serum amylase or lipase >1.5 x ULN * Total bilirubin >1.5 x ULN * Aspartate aminotransferase or alanine aminotransferase >=2.5 x ULN * Eastern Cooperative Oncology Group (ECOG) performance status (PS) >2 at study entry. * Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of study drug. * Ongoing or recent history (within 3 months of Day 1 Segment 1) of clinically significant dysrrhythmia. * Patients taking a beta blocker within 7 days to Day 1 Segment 1 and during Segment 1 * Other concurrent serious illness or medical condition, including active infection or HIV disease. * Patients with known active (acute or chronic) Hepatitis A, B, C, and hepatitis B and or C carriers. Prior history of chronic liver disease. * Patients with history of partial or total gastrectomy, or, if in the opinion of the investigator, have any other disorder that would inhibit absorption of oral medications. * Any severe acute or chronic medical, neurological, or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, or may interfere with interpretation of study results and, in the Investigator's opinion, would make the patient inappropriate for entry into this study. * Contra-indications for palonosetron. * Use of drugs or herbal agents known to be at least moderate inhibitors or inducers of CYP3A4, sensitive CYP3A4 substrate, or CYP3A4 substrate with narrow therapeutic index, within 2 weeks of Day 1 and during study. * Concomitant treatment with H2-blockers is not allowed within 7 days prior to Day 1 Segment 1 and during entire study. * Known hypersensitivity to any excipients in IMP formulations. * Pregnant or lactating females * Women of childbearing potential, unless using effective contraception (other than oral contraceptives) while on study drug. Men who partner with a woman of childbearing potential, unless they agree to use effective contraception while on study drug The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Objectives The purpose of this study is to assess the drug-drug interaction (DDI) of either esomeprazole or rifampin on the single-dose PK of alisertib, and to complete an intensive QT study of single and multiple-dose alisertib. Conditions: Solid Tumors, Lymphoma Intervention / Treatment: DRUG: Alisertib, DRUG: Esomeprazole, DRUG: Rifampin Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Male or female participants >= 18 years * Histologically or cytologically confirmed metastatic and/or advanced solid tumors or lymphomas * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Expected survival longer than 3 months from enrollment in the study * Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse * Male participants who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse Exclusion Criteria: * Treatment with any anticancer therapy or any investigational agents within 4 weeks before the first dose of alisertib - Known hypersensitivity or intolerance to rifampin (for participants considered for the rifampin drug-drug interaction [DDI] group) or to esomeprazole (for participants considered for the esomeprazole DDI group) * Recurrent nausea and/or vomiting within 14 days before the first dose of alisertib, and known gastrointestinal (GI) abnormality or GI procedure that could interfere with or modify the oral absorption or tolerance of alisertib * Participants requiring treatment with clinically significant enzyme inducers within 14 days before the first dose of alisertib and/or requiring the use of these medications during the study * A medical condition requiring use of pancreatic enzymes; or daily, chronic, or regular use of proton pump inhibitors (PPI); or histamine (H2) receptor antagonists * Participants requiring systemic anticoagulation (excluding low-dose aspirin, or low-dose anticoagulation to maintain patency of venous access devices). * Any cardiovascular condition * Female participants who are lactating or have a positive serum pregnancy test * Major surgery within the 14 days preceding the first dose of alisertib - Life-threatening or uncontrolled medical illness unrelated to cancer * Newly diagnosed or uncontrolled cancer-related central nervous system (CNS) disease * Autologous stem cell transplant within 3 months * Prior allogeneic bone marrow or other organ transplantation - Other severe acute or chronic medical or psychiatric condition * Known or suspected human immunodeficiency virus (HIV) positive or hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection Please note there are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.

Study Objectives To demonstrate the superiority of paricalcitol treatment at early renal post-transplantation (M6) in the control of iPTH (Intact parathyroid hormone) compared to the use of vitamin D nutritional supplements (calcifediol) in patients with renal transplantation. Conditions: Secondary Hyperparathyroidism Due to Renal Causes Intervention / Treatment: DRUG: Paricalcitol, DRUG: Calcifediol Location: Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patient that have willingly signed and dated the ICD (Informed Consent Document) approved by the EC (Ethics Committee) before any study procedure and after they have been explained the study, they have read the ICD and have had the opportunity to make questions about it. * Patients of both genders and older than 18 years candidates to an immediately renal transplantation from living or deceased donor. * 24 hours previous to the transplantation, patient must have a significant grade of secondary hyperparathyroidism, defined as iPTH (Intact parathyroid hormone) levels between 110 and 600 pg/mL as per central laboratory results. * Patients with a preformed antibody panel <20% 24 hours before the transplantation or that are considered by the investigator of low immunological risk (PRA determination is being done on local laboratory, not central). * Serum calcium (corrected by albumin) < 10 mg/dL 24 hour previous to the transplantation as per central laboratory results. * Patients that are to be treated with immunosuppression based on tacrolimus, mofetil mycofenolate or mycophenolic acid and with steroids and that are not going to be treated with mTOR (mammalian target of rapamycin) inhibitors. Tacrolimus and steroids must not be removed on the 6 month post-transplantation. * Patients that are able to take oral capsules on the first week post-transplantation. Exclusion Criteria: * Third or subsequent renal transplantation. * Positive cross-match assay or ABO (A-B-0) incompatibility * Patients that have been or are going to be recipients of other organs other than the kidney or a double kidney transplantation. * Patients with history of allergic reaction or sensibility to paricalcitol, calcifediol or similar study drugs (related with vitamin D). * Patients with chronic gastrointestinal disease, that, based on investigators criteria, can cause significant gastrointestinal malabsorption. * Patient with hypo or hyperthyroidism not controlled based on investigators criteria. * Patient with uncontrolled hypertension based on investigators criteria. * Patients that, 48 hours previous to transplantation, have been receiving calcimimetics. * Patients with VIH (human immunodeficiency virus)infection of positive serology for HBV (hepatitis B virus) and/or HCV (hepatitis C virus) * Patients on treatment with drugs contraindicated with paricalcitol and calcifediol (based on SMPC) * Patients that are participating on other clinical trial with investigational drugs. * Women of childbearing potential (defined as those whose last menstruation was <2 years ago and that are not surgically sterilized) that are not willing to use correct contraception during study treatment. * Patient with other diseases or conditions that based on investigators criteria are not suitable for the study. * Treatment will not be started if the Calcium-Phosphorus product (CAxP)is >55 mg2/dL2 or in case of hyperphosphatemia considered significant as per investigator criteria

Study Objectives No clinical trials with PBF-509 in humans have been performed to date. Only preclinical studies have been done to assess the pharmacology and pharmacokinetics, the safety and the toxicological profile of the PBF-509. An initial testing of PBF-509 in humans is planned, starting with the first-into-man clinical trial where a single oral, dose-escalating, and placebo-controlled design will be implemented. Conditions: Parkinson Disease Intervention / Treatment: DRUG: PBF-509, DRUG: Placebo Location: Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Each subject must meet all of the following inclusion criteria at the pre-study screening visit (within 4 weeks prior to dosing) in order to participate in this study. * Healthy male subjects, 18-45 years of age. * Clinically acceptable blood pressure and pulse rate in supine and standing position. Blood pressure and pulse will be measured after a minimum of 3 minutes of resting. * Body weight within normal range (Quetelet's index between 19 and 26) expressed as weight (kg) / height (m2).. * Non-smokers (refrained from any tobacco usage, including smokeless tobacco, nicotine patches, etc., for 6 months prior to the administration of the study medication). * Able to understand the nature of the study and comply with all their requirements. * Free acceptance to participate in the study by obtains signed informed consent form approved by the Ethics Committee of the Hospital (CEIC). Exclusion Criteria: * History of serious adverse reactions or hypersensitivity to any drug. * Presence or history of allergies requiring acute or chronic treatment (except seasonal allergic rhinitis). * Background or clinical evidence of chronic diseases. * Acute illness two weeks before drug administration. * Having undergone major surgery during the previous 6 months. * History of alcohol or drug abuse in the last 5 years. * Abnormal physical findings of clinical significance at the screening examination or baseline which would interfere with the objectives of the study. * Need of any prescription medication within 14 days prior to the administration of the drug and non prescription medication or herbal medicines within 7 days prior to the administration of the drug. * Participation in other clinical trials during the previous 90 days in which an investigational drug or a commercially available drug was tested. * Not having donated blood during 3 month period before inclusion in the study. * Existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the drug, i.e. impaired renal or hepatic function, diabetes mellitus, cardiovascular abnormalities, chronic symptoms of pronounced constipation or diarrhea or conditions associated with total or partial obstruction of the urinary tract. * 12 lead ECG obtained at screening with PR > 220 msec, QRS>120 msec and QTc >440 msec, bradycardia (<50 bpm) or clinically significant minor ST wave changes or any other abnormal changes on the screening ECG. * Symptoms of a significant somatic or mental illness in the four week period preceding drug administration. * History of hepatitis B and / or C and / or positive serology results which indicate the presence of hepatitis B and / or C. * Positive results from the HIV serology. * Clinically significant abnormal laboratory values (as determined by the Principal Investigator) at the screening evaluation. * Positive results of the drug screening the day before starting treatment period. * Known hypersensitivity to the study drug or the composition of the galenical form * History of psychiatric diseases or epileptic seizures

Study Objectives The purpose of this study is to determine the effectiveness and side effects of a new combination and schedule of chemotherapy drugs in the treatment of head and neck cancer. Patients with advanced or recurrent head and neck cancer, which is untreatable by surgery or radiation therapy are eligible for this study. Standard treatment for advanced or recurrent head and neck cancer involves the use of chemotherapy. Conditions: Head and Neck Cancer Intervention / Treatment: DRUG: Docetaxel, DRUG: Capecitabine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must have documented advanced, locally recurrent, or metastatic head and neck carcinoma, which is untreatable by surgical resection or radiation therapy. * Prior chemotherapy for advanced/metastatic disease is allowed (1 regimen only). * Patients must be taxane-naïve (no prior docetaxel or paclitaxel). * Patients who have received chemoradiation as a primary therapy for advanced head and neck cancer are eligible. * Patients must have measurable or evaluable disease. Pre-study imaging for disease assessment must be done within 28 days of registration. * Patients with brain metastases are eligible if they have been stable for at least six weeks post-radiation therapy. * Aged >= 18 years * Performance status of 0-2 by Zubrod criteria. * Life expectancy of at least 12 weeks. * Hematologic: absolute neutrophil count (ANC) equal to or > 1,500/mm3; hemoglobin equal to or > 8.0 g/dl; platelets equal to or > 100,000/mm3. * Total bilirubin must be within normal institutional limits (WNL). * Transaminases (AST/SGOT and ALT/SGPT) may be up to 2.5 X the institutional upper limit of normal (ULN) if alkaline phosphatase is less than ULN, or alkaline phosphatase may be up to 4 X ULN if transaminases are less than ULN. * A calculated creatinine clearance of > 50 ml/min * Women of childbearing potential must have a negative pregnancy test at baseline, prior to receiving any study drug. (Pregnant or lactating patients are excluded.) * Patients of reproductive potential must practice effective contraception while on study and for at least six months after receiving the last dose of study drug. * All patients must sign an informed consent prior to enrollment. * No prior history of malignancy, except for adequately treated skin cancer or in situ cervical carcinoma or any other cancer in complete remission for at least two years. Exclusion Criteria: * Patients with congestive heart failure, second or third degree heart block or recent myocardial infarction within 12 months from registration are not eligible. * Peripheral neuropathy equal to or greater than grade 2. * Patients with a history of severe hypersensitivity reaction to drugs formulated with polysorbate 80. * Use of standard chemotherapy or investigational agents for treatment of head and neck cancer within 28 days of 1st dose of study drug. * Any medical or psychiatric illness which, in the opinion of the principal investigator, would compromise the patient's ability to tolerate this treatment regimen. * Prior unanticipated severe reaction to fluoropyrimidine therapy or known hypersensitivity to 5-fluorouracil. * Pregnant or lactating women, women of childbearing potential with either a positive pregnancy test (PPT) at baseline, or sexually active females not using a reliable contraceptive method while on study and for at least six months after chemotherapy. (Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.) * Sexually active patients not using a reliable contraceptive method while on study and for at least six months after chemotherapy. * Patients with malabsorption syndromes will be excluded. Administration of capecitabine through feeding tubes is permitted. * Serious concurrent infections. * Any other serious uncontrolled medical or surgical conditions that the investigator feels might compromise study participation.

Study Objectives The purpose of our study was to conduct a placebo controlled, double-blind randomized trial in chronic oligoovulatory or anovulatory , hyperandrogenic, infertility patients comparing the effects of adjuvant metformin plus clomiphene citrate to clomiphene citrate plus placebo on pregnancy rates and ovulation rates. We hypothesized that combining metformin with clomiphene citrate would result in higher ovulation and pregnancy rates in hyperandrogenic women who have chronic oligoovulation or anovulation as the sole etiology for their infertility and who have unknown responsiveness to clomiphene citrate. Conditions: Polycystic Ovary Syndrome, Anovulation, Oligoovulation, Infertility, Hyperandrogenism Intervention / Treatment: DRUG: Metformin, DRUG: Clomiphene citrate, DRUG: Placebo Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Married * Hyperandrogenic women 18-40 years old who desired fertility and who demonstrated chronic anovulation or oligoovulation * Had patent fallopian tubes and whose partners had normal semen analyses were eligible for enrollment in the study. Exclusion Criteria: * Androgen secreting tumours * Diabetes mellitus * Thyroid abnormalities * Hyperprolactinemia * Adult onset congenital adrenal hyperplasia * Diminished ovarian reserve * Subjects who used hormonal medications two months prior to the start of the trial.

Study Objectives The purpose of this study is to find out what effects, good and/or bad STA-9090 has on colorectal cancer. This is a phase II trial which tests both how well the drug works in fighting your cancer as well as any possible side effects it will have on the patient. Cancer is a disease of uncontrolled growth. This growth is controlled in part by a series of proteins that are part of a growth pathway. Some of these proteins are destroyed by a protein called HSP90 and STA-9090 is a test drug which blocks one of the proteins that helps cancer grow. This study will also look at molecular markers that may affect how the cancer grows, and how it responds to treatment. Conditions: Colon Cancer, Rectal Cancer Intervention / Treatment: DRUG: STA-9090 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: * The patient has histologically or cytologically-confirmed colorectal cancer with metastatic disease documented on diagnostic imaging studies. * The patient has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded), measuring >=20 mm on conventional measurement techniques or >=10 mm on spiral computed tomography (CT) scan. * The patient has received at least one prior standard and/or investigational regimen for metastatic disease. * The patient is age >=18 years. * The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 (Karnofsky>= 80%). * The patient has adequate hematologic function as defined by an absolute neutrophil count >=1500/μL, hemoglobin >=9/μdL, and a platelet count >=100,000/μL. * The patient has adequate hepatic function as defined by a total bilirubin <= 2.5x the upper limit of normal (ULN), and aspartate transaminase (AST) and alanine transaminase (ALT)<=3 x the ULN (or <=5 x the ULN in the presence of known liver metastases). * The patient, if not on anticoagulation, has adequate coagulation function as defined by international normalized ratio (INR) <=1.5 ULN and partial thromboplastin time (PTT) <=1.5x the ULN. Patients on full-dose anticoagulation must be on a stable dose of oral anticoagulation or low molecular weight heparin, must have an INR value within acceptable range for treatment and have no active bleeding or pathological condition that, in the opinion of the investigator, carries a high risk of bleeding. * The patient has adequate renal function as defined by serum creatinine <=1.5 x the institutional ULN or creatinine clearance >=60 mL/min for patients with creatinine levels above 1.5, as well as urine protein <=1+ on routine analysis (if routine UA indicates >=2+ protein, a 24-hour urine collection for protein must demonstrate < 1000mg of protein in 24 hours to allow participation in the study). * The patient has a life expectancy of > 3 months. * Because the teratogenicity of STA-9090 is not known, men and women of childbearing potential must agree to use adequate contraception (hormonal or barrier birth control; abstinence) prior to study entry and for the duration of study participation. * The patient has the ability to read and willingness to sign informed consent. * For stage I of the protocol (the first 15 patients) the tumor must be amenable to biopsy and the patient must be willing to undergo pre and post treatment biopsies. * The patient must have a normal QTc interval on baseline ECG , (<470 milliseconds, males and females). Exclusion Criteria: * Patient may not have received chemotherapy within 4 weeks prior to entering the study, and must have recovered (to grade 1 or less) from adverse events due to agents administered. * Primary brain tumors or active brain metastases. However, patients with a history of CNS metastases will be eligible if they have been treated and are stable for 4 weeks after completion of treatment, with image documentation required, and must be either off steroids or on a stable dose of steroids for a minimum of 2 weeks prior to enrollment. * History of stroke within 6 months of treatment or other significant neurological limitations. * Major surgery within 4 weeks prior to entering the study. * Poor venous access for study drug administration or would require a peripheral or central indwelling catheter for study drug administration. Study drug administration via indwelling catheters is prohibited at this time. * Use of any investigational agents within 4 weeks prior to entering the study. * History of severe allergic reactions to excipients (e.g., Polyethylene glycol 300 and Polysorbate 80), including severe hypersensitivity reactions defined as >= Grade 3 based on NCI CTCAE version 3. * Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation or systemic steroids for treatment of autoimmune disease). However, patients may receive steroids for stable CNS metastases as described in exclusion criterion 2. * Uncontrolled intercurrent illness including, but not limited to, human immunodeficiency virus (HIV)-positive patients receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug 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. * Ventricular ejection fraction (Ef) <= 45%. * Inaccessible tissue for biopsy (first 15 patients only) * History of or current coronary artery disease, myocardial infarction, angina pectoris, angioplasty or coronary bypass surgery * History of or current uncontrolled dysrhythmias, or requirement for antiarrhythmic medications, or Grade 2 or greater left bundle branch block * New York Heart Association class II/III/IV congestive heart failure with a history of dyspnea, orthopnea or edema that requires current treatment with angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers or diuretics * Current or prior radiation therapy to the left hemithorax

Study Objectives This study evaluates PGE2 production, COX-2 enzyme activity and PCNA expression in Barrett's metaplastic tissue. All patients will have a baseline endoscopy with multiple biopsies. The patients will then be receive four dosing regimens (esomeprazole, esomeprazole and aspirin, esomeprazole and rofecoxib, or rofecoxib alone) consecutively each for a 10 day dosing period, whilst undergoing further follow up endoscopies and multiple biopsies. Conditions: Barrett's Esophagus Intervention / Treatment: DRUG: Esomeprazole, DRUG: Aspirin, DRUG: Rofecoxib Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: NONE

Inclusion Criteria: * A biopsy-proven diagnosis of Barrett's esophagus segment length greater than 2cm with no dysplasia or adenocarcinoma. * Clinically normal laboratory results and physical findings at screening. Exclusion Criteria: * A history of esophageal, gastric or duodenal surgery, including antireflux surgery or endoscopic antireflux procedures, except for simple closure of an ulcer. * Evidence of the following diseases or conditions: * Barrett's esophagus less than or greater than 2cm that is positive for high grade dysplasia or adenocarcinoma * Signs and symptoms of gastric outlet obstruction * Active peptic ulcer disease * severe liver disease * Pancreatitis * Malabsorption * Active inflammatory bowel disease * Severe pulmonary, cardiovascular or renal disease * Impaired renal function or abnormal urine sediment on repeated examinations * esophageal stricture or active, severe esophagitis.

Study Objectives The study evaluated the safety of Lenalidomide monotherapy in participants with advanced multiple myeloma who had discontinued treatment with combination thalidomide plus high-dose dexamethasone or high-dose dexamethasone alone in studies Thal-MM-003, CC-5013-MM-009 and CC-5013-MM-010 due to the development of documented disease progression or the inability to tolerate the lowest dosing regimen per previous protocol of thalidomide and/or high-dose dexamethasone without grade 3 or 4 toxicity. Conditions: Multiple Myeloma Intervention / Treatment: DRUG: CC-5013, DRUG: Lenalidomide Location: Ukraine, Russian Federation Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Understand and voluntarily sign an informed consent form. * Age >= 18 years at time of signing the informed consent form. * Able to adhere to the study visit schedule and other protocol requirements * Participants with multiple myeloma and were enrolled in either THAL-MM-003, CC-5013-MM-009, or CC-5013-MM-010 and discontinued study therapy with thalidomide and high-dose dexamethasone or high-dose dexamethasone alone due to: documented disease progression OR inability to tolerate the lowest dosing regimen allowed on previous protocol without a grade 3 or 4 toxicity. * Eastern Cooperative Oncology Group (ECOG) performance status score 0,1,2 * Recovery from thalidomide or dexamethasone-related toxicity to <= grade 2 (NCI CTC) * Females of child-bearing potential (FCBP) must agree to using two methods of contraception Exclusion Criteria: * Prior development of a >= grade 2 allergic reaction/hypersensitivity or prior development of a grade >= 3 rash or desquamation while taking thalidomide National Cancer Institute Common toxicity Criteria (NCI CTC) * Use of any standard/experimental anti-myeloma therapy within 28 days of randomization or use of any experimental non-drug therapy within 56 days of initiation of drug treatment * Any serious medical condition, laboratory abnormality, or psychiatric illness that will prevent the participant from signing the informed consent form or that will place the participant at an unacceptable risk for toxicity if he/she participates in the study. * Pregnant or lactating females. * Prior therapy with CC-5013; prior history of malignancies, other than multiple myeloma (except basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast), unless subject has been free of disease for >= 5 years * More than 4 months has elapsed since the last dose of study drug was administered on study Tal MM-003, CC-5013-MM-009, CC-5013-MM-010 * Absolute neutrophil count (ANC) <1,000cells/mm^3 (1.0 X 10^9/L) * Platelet count <75,000/mm^3 (30 X 10^9/L) for those with <50% if the bone marrow nucleated cells re plasma cells; Platelet count <30,000/mm^3 (30 X 10^9/L) for those with <50% if the bone marrow nucleated cells re plasma cells * Serum creatinine >2.5mg/dL; serum SGOT/AST or SGPT/ALT x upper limits of normal (ULN) * Serum total bilirubin >2.0mg/d/L

Study Objectives LEP-ETU is a novel, proprietary delivery system of paclitaxel developed by NeoPharm, Inc. Paclitaxel (currently marketed as Taxol) is an anti-microtubular network agent and is active in a broad spectrum of malignancies. Paclitaxel has poor solubility. In order to enhance the solubility, this drug is formulated with polyoxyethylated castor oil, which leading to infusion-related hypersensitivity reactions. The NeoPharm LEP-ETU is formulated with a mixture of well characterized, synthetic phospholipids and cholesterol. This design eliminates the need for the oil. The LEP-ETU formulation has improved safety profile that is necessary for administering higher doses than would commonly be used with Taxol. The clinical evidence obtained from the NeoPharm Phase I study shows LEP-ETU is better tolerated than Taxol, as indicated by a higher maximum-tolerated dose (MTD). The current Phase II study is designed to accomplish the following objectives: 1. Assess the Overall Response Rate (ORR) of patients with metastatic breast cancer after administered over 90 minutes at the dose of 275 mg/m2 LEP-ETU 2. To evaluate the Progression-Free Survival (PFS) 3. To evaluate the safety of LEP-ETU at 275 mg/m2 level, in particular peripheral neuropathy 4. To evaluate the Overall Survival (OS) Conditions: Breast Cancer Intervention / Treatment: DRUG: LEP-ETU Location: India Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Be >= 18 years and female. * Have histologically or cytologically confirmed diagnosis of invasive adenocarcinoma originating in the breast. * Have at least one target lesion per RECIST criteria * If the patient has received adjuvant or neoadjuvant taxane therapy, the patient must not have relapsed with breast cancer within one year of completing this therapy. * Have received prior chemotherapy in the adjuvant or metastatic setting with an anthracycline unless contraindicated. * Have no other malignancy within the past five years, except non-melanoma skin cancer, cervical intraepithelial neoplasia (CIN), or in-situ cervical cancer (CIS). * Have the following hematology levels at Baseline: * ANC greater than or equal to 1,500 x 106 cells/L; * Platelets greater than or equal to 100 x 109 cells/L; * Hgb greater than or equal to 90 g/L. * Have the following chemistry levels at Baseline: * AST (SGOT), ALT (SGPT) less than or equal to 2.5 x ULN if no evidence of liver metastases; * AST (SGOT), ALT (SGPT) less than or equal to 5 x ULN if liver metastases are present; * Total bilirubin less than or equal to 26 micromol/L (1.5 mg/dL); * Creatinine less than or equal to 177 micromol/L (2 mg/dL); or 24-hour * Alkaline phosphatase less than or equal to 5 x ULN (unless bone metastasis is present in the absence of liver metastasis). * Have a life expectancy of greater than or equal to 12 weeks. * Have an ECOG Performance status of 0-2. * Patients of child-bearing potential must agree to use acceptable contraceptive methods (e.g., double barrier) during treatment. * Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee -approved written informed consent form prior to receiving any study related procedure. Exclusion Criteria: * Patient has radiographic evidence of active (symptomatic, untreated) intraparenchymal brain metastases; any leptomeningeal metastases; or asymptomatic untreated intraparenchymal brain metastases requiring treatment. * Patient has received more than 1 prior treatment with a non-taxane agent in the metastatic setting. * The only evidence of metastasis is lytic or blastic bone metastases or pleural effusion or ascites. * Patient has a known infection with human immunodeficiency virus or active viral hepatitis. * Patient has active heart disease including myocardial infarction or congestive heart failure within the previous 6 months, symptomatic coronary artery disease, or uncontrolled arrhythmias. * Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug (e.g., uncontrolled bleeding or bleeding diathesis). * Any active infection requiring parenteral or oral antibiotics. * The patient receives treatment with any: * Hormonal or other non-investigational agent therapy within 2 weeks prior to first dose of study drug; * Herceptin, mitomycin, or nitrosoureas therapy within 6 weeks prior to first dose; * Chemotherapy (except for palliative bisphosphonate therapy for bone pain which can be administered as clinically indicated) within 4 weeks prior to first dose study drug; * Investigational drug or immunotherapy within 4 weeks prior to first dose study drug; * Concurrent radiation therapy (except for palliative radiotherapy for * Radiation therapy within 4 weeks prior to first dose of study drug. * Patient has pre-existing peripheral neuropathy of NCI-CTCAE Grade >1. * Patient has received paclitaxel, docetaxel, or Abraxane because of metastatic carcinoma. * Known hypersensitivity to paclitaxel, Cremophor EL, or liposomes. * Pregnant or nursing female patients. * Unwilling or unable to follow protocol requirements.

Study Objectives The purpose of this study is to evaluate the efficacy and safety of the combination of study drugs encorafenib, binimetinib and cetuximab in patients who have BRAF V600 mutant metastatic colorectal cancer and have not received any prior treatment for their metastatic disease. Conditions: BRAF V600E-mutant Metastatic Colorectal Cancer Intervention / Treatment: DRUG: encorafenib, DRUG: Binimetinib, DRUG: Cetuximab Location: Japan, Italy, Netherlands, Spain, United Kingdom, United States, Belgium, Austria, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Male or female >= 18 years of age * Histologically or cytologically confirmed CRC that is metastatic * Presence of BRAF V600E in tumor tissue determined by local assay at any time prior to screening * Evidence of measurable disease as per RECIST, v1.1 * Subject able to receive cetuximab as per approved label with regards to RAS status * Eastern Cooperative Oncology Group Status (ECOG) 0 or 1 * Adequate renal, hepatic, cardiac and bone marrow functions and adequate electrolytes as per protocol * Subject able to take oral medications Exclusion Criteria: * Prior systemic therapy for metastatic disease * Prior treatment with any RAF inhibitor, MEK inhibitor, cetuximab or other anti-EGFR inhibitors * Symptomatic brain metastasis or Leptomeningeal disease * History or current evidence of Retinal Vein Occlusion (RVO) or current risk factors for RVO * History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) <= 12 months prior to first dose. * Impaired cardiovascular function or clinically significant cardiovascular diseases: history of myocardial infarction or coronary disorders within 6 months prior to start of study treatment, symptomatic congestive heart failure (grade 2 or higher), past or current clinically significant arrhythmia and/or conduction disorder within 6 months prior to study treatment start * History of thromboembolic or cerebrovascular events within 6 months prior to start of study treatment * Concurrent neuromuscular disorder that is associated with potential elevation of Creatine Kinase * Known contraindication to cetuximab administration as per SPC/approved label

Study Objectives Longer first line chemotherapy duration has recently been associated with a modest, but significant improvement in overall survival and a clinically meaningful and statistically significant improvement in progression-free survival, in metastatic breast cancer patients. Prolonging chemotherapy until disease progression, however, must be weighed against the detrimental effects of continuous chemotherapy delivery. The SNAP trial seeks to improve the tolerability of prolonged chemotherapy administration strategy by studying alternative treatment schedules, while preserving and possibly improving treatment efficacy in this disease setting. The availability of a new nanoparticle albumin-bound taxane, nab-Paclitaxel (Abraxane®), represents an opportunity to test this hypothesis. Nab-Paclitaxel has been developed in an attempt to reduce the toxicity associated with standard taxane administration (caused by the use of chemical solvents) while increasing antitumor efficacy. The SNAP randomized phase II trial evaluates three schedules of nab-Paclitaxel as prolonged chemotherapy administration strategy. Each of three arms will be compared to a historical reference of seven-month median progression-free survival (PFS) based on the most recent trial with docetaxel as control arm to determine whether any of the three arms are worthy of further investigation. Conditions: Metastatic Breastcancer Intervention / Treatment: DRUG: nab-Paclitaxel Location: Spain, Italy, Switzerland, Belgium, Slovenia, Ireland 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 HER2-negative metastatic (stage IV) breast cancer. * Measurable or non-measurable, but radiologically evaluable, disease according to RECIST 1.1 criteria. * Female aged >= 18 years. * Life expectancy > 3 months. * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. * Either ER-positive or ER-negative disease. Patients with ER-positive disease must be endocrine resistant, defined as having failed at least one prior endocrine therapy for breast cancer, or must be candidates for first-line chemotherapy. * If previously treated with a taxane or anthracycline in the neoadjuvant or adjuvant setting, the period from end of treatment to disease recurrence must have been > 12 months (> 365 days). * Radiation therapy, if given and regardless of site, must be completed at least 2 weeks prior to randomization. * Normal hematologic status. * Normal renal function. * Normal liver function. * Normal cardiac function. * Women of childbearing potential: documented negative pregnancy test within 2 weeks prior to randomization, and acceptable birth control during the duration of the trial therapy and for a period of 6 months following the last administration of study drug. * Written Informed Consent (IC) must be signed and dated by the patient and the Investigator prior to randomization. * Completed baseline Quality of Life Form. * The patient has been informed of and agrees to data transfer and handling, in accordance with national data protection guidelines. * Availability of an formalin fixed paraffin embedded (FFPE) block from the primary tumor (breast lesion) for submission to central pathology review and for translational research. * Written consent to pathology material submission, signed and dated by the patient and the Investigator prior to randomization. Exclusion Criteria: * Any prior chemotherapy for metastatic breast cancer. * Presence of central nervous system (CNS) metastasis. * Peripheral neuropathy grade 2 or higher (CTCAE version 4). * Significant uncontrolled cardiac disease (i.e. unstable angina, recent myocardial infarction within prior 6 months), patients classified as having a New York Heart Association (NYHA) class III or IV congestive heart failure. * Pregnant or lactating. * Prior history of non-breast malignancy (except for adequately controlled basal cell carcinoma of the skin, carcinoma in situ of the cervix, in situ carcinoma of the bladder). * Any concurrent condition which in the Investigator's opinion makes it inappropriate for the patient to participate in the trial or which would jeopardize compliance with the protocol. * Contraindications or known hypersensitivity to the study medication or excipients. * The use of any anti-cancer investigational agents within 30 days prior to expected start of trial treatment. * Inability or unwillingness to abide by the study protocol or cooperate fully with the Investigator.

Study Objectives This is a prospective, randomized, controlled, unblinded, parallel, multicenter, and non-inferiority study to demonstrate the safety and efficacy of a Food for Special Medical Purpose product (FSMP) in participants with digestive tract tumor undergoing surgical resection during the perioperative period. Conditions: Gastrointestinal Cancer Intervention / Treatment: OTHER: Experimental Product, OTHER: Control Product Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: OTHER Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Participant is male or female, between 18 and 75 years old, female participant is non-pregnant or non- lactating, at least 6 weeks postpartum * Participants with digestive tract tumors diagnosed by histological method or radiological diagnosis and scheduled to undergo surgical resection * Participant with NRS-2002 score >=3 * Participant is willing to comply with the study protocol, able and willing to consume study product according to the protocol * Participants with Body Mass Index 18.5 - 30 kg/m2 * Participant has voluntarily signed and dated an informed consent form (ICF), approved by an Institutional Review Board (IRB) / Independent Ethics Committee (IEC) prior to any participation in the study Exclusion Criteria: * Participant has an expected life expectancy < 3 months * Participant has contraindications to enteral nutrition (such as active gastrointestinal hemorrhage, bowel obstruction, decompensated short bowel syndrome, high flow intestinal fistula, severe intraperitoneal infection, severe gastrointestinal emptying disorder, unstable vital signs, dyscoagulation, severe nausea, vomiting and/or uncontrolled diarrhea/steatorrhoea) that in the opinion of the study physician cannot be corrected * Participant used parenteral nutrition or had plasma infused, RBC infused, albumin infused, amino acid infused or undergone radiotherapy and/or chemotherapy within 1 week before screening * Participant with serum Albumin <2.5g/dl at the time of the screening * Participant has moderate to severe anemia, i.e. Hgb < 90g / L * Patients who plan to receive endoscopic tumor resection or / and palliative surgery * Participant has renal dysfunction (serum creatinine > 2 times the upper limit of normal (ULN)) * Participant has liver insufficiency [serum alanine transaminase (ALT) and/or aspartate transaminase (AST) > 2 times the ULN or severe cholestasis (conjugated bilirubin > 2 times the ULN)] * Participant has severe cardiac insufficiency (e.g., Severe arrhythmia or atrial fibrillation; myocardial ischemia or stent surgery with unstable cardiac function within 3 months prior to screening visit ) * Participant states that he/she has had a significant cardiovascular and cerebrovascular event (e.g., myocardial infarction, stroke) within six months prior to screening visit; or stated history of congestive heart failure * Participant with type I diabetes, or type II diabetes with fasting blood glucose >=8mmol/L * Participant has history of significant neurological or psychiatric disorder * Participant has history of alcoholism, drug abuse or other conditions that may interfere with study product consumption or compliance with study protocol procedures * Participant has a known history of allergy or intolerance to any ingredient in the investigational products * Participant is currently undergoing tumor immunotherapy taking medications/substances that could profoundly modulate appetite, metabolism or inflammatory level 1. Appetite enhancers, pregnancy promoters, steroids (nasal inhalation, topical and optical steroids are acceptable); 2. Anti-inflammatory fat emulsions or other oral nutritional supplementations/drugs containing Omega-3 fatty acids, protein, glutamine, or arginine. 3. Dexamethasone, growth hormone or other drugs affecting metabolism; * Participant is currently undergoing tumor immunotherapy or taking medications/substances that could profoundly modulate immune function, such as PD1 or PDL1 inhibitors; CTLA-4 inhibitor; Thymosin; Azathioprine; Cyclosporine; Tacrolimus; Tumor necrosis factor antagonist; Lentinan; immune-modulating Chinese medicine * Participant with active tuberculosis and HIV infection * Participant participated in any clinical trial within four weeks prior to the screening visit.

Study Objectives Paclitaxel covered metal biliary stent extents their patency rate comparing to the Common Covered Metallic Biliary Stent. Conditions: Biliary Stricture, Malignant Neoplasms Intervention / Treatment: DEVICE: Biliary stent Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * Patient who is inoperable and/or unresectable cases of pancreatic cancer and/or biliary cancer with mid or distal CBD invasion * Among patient of a.,Patient who previously had surgical biliary drainage of plastic stent have eligibility Exclusion Criteria: * Patient who have life expectancy under 3 months * Patient who have severe metastasis of Liver or whole body * Patient who previously had surgical biliary drainage

Study Objectives To determine the safety and feasibility of 89Zr-Df-IAB22M2C as an immunoPET tracer; determine the best time window and protein dose for imaging; determine the pharmacokinetic (PK) and biodistribution of the probe; and to determine imaging parameters for optimal lymphoid and tumor visualization. Conditions: Positron-Emission Tomography, Immunomodulation, Metastatic Solid Malignancies, Hodgkin Lymphoma Intervention / Treatment: DRUG: ⁸⁹Zr-Df-IAB22M2C Infusion 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: * Patients with selected solid malignancies (NSCLC, SCLC, SqCCHN, melanoma, merkel cell tumor, renal, bladder, hepatocellular, triple negative breast, or gastroesophageal cancer) or Hodgkin's lymphoma * At least 1 measurable lesion documented on CT/MRI (RECIST criteria 1.1) * Eastern Cooperative Oncology Group (ECOG) performance status <= 2 (Appendix B: ECOG Scoring) * Age >= 18 years * Ability to understand the purposes and risks of the trial and has signed a IRB-approved informed consent form * Willingness and ability to comply with all protocol required procedures * For men and women of child-bearing potential, use of effective contraceptive methods during the study Exclusion Criteria: Patients meeting any of the following criteria will not be eligible for study entry: * Known infection with human immunodeficiency virus (HIV) * Serious nonmalignant disease or conditions that in the opinion of the investigator and/or ImaginAb could compromise protocol objectives * Patients who have had splenectomy. * Patients who have any splenic disorders that in the opinion of the investigator and/or ImaginAb could compromise protocol objectives. * Patients who are currently receiving any other investigational agent * Pregnant women or nursing mothers * Hepatic laboratory values: 1. Bilirubin > 1.5 x ULN (institutional upper limits of normal) 2. Albumin < 2 g/dL 3. Other local safety laboratory test results (clinical chemistry and hematology) are determined to be exclusionary by the Investigator. * Known sensitivity to glutamic acid or glutamate.

Study Objectives Berberine hydrochloride is a conventional component in Chinese medicine. In recent years, anticancer activity of berberine hydrochloride have been explored. The aim of this study is to investigate the effect of berberine hydrochloride on the recurrence of colorectal adenomas. Conditions: Colorectal Adenoma Intervention / Treatment: DRUG: Berberine hydrochloride, DRUG: placebo Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2, PHASE3 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion criteria * Individuals aged 18-75 years * Individuals who had at least one and no more than 6 histologically confirmed CRAs removed within 6 months before recruitment * Individuals who are able to swallow pills * Individuals who voluntarily sign the consent form after being fully informed and understanding the purpose and procedure of this study, characters of the disease, effect of medication, methods of related examinations, and potential risk/benefits of the study 4.2 Exclusion criteria * Individuals whose adenoma was not completely removed during previous colonoscopy * Individuals with a history of familial adenomatous polyposis (FAP) or hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome) * Individuals who are taking regularly aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclo-oxygenase 2 (COX2) inhibitors, calcium or vitamin D * Individuals with a history of subtotal/total gastrectomy or partial bowel resection * Individuals who are intolerant to another colonoscopy examination * Individuals who are hypersensitive or intolerant to the drugs * Individuals with severe heart, liver or kidney disease, or any cancer history * Individuals presenting severe constipation * Pregnant women, women during breast-feeding period, or women with expect pregnancy * Individuals with mental diseases who are not able to cooperate * Individuals who are involved in designing, planning or performing this trial

Study Objectives The purpose for this study is to see if the study drug, LY3484356, is safe and to determine what effects it has on breast cancer in participants with Estrogen Receptor Positive (ER+), HER2 Negative (HER2-) early stage (stage I-III) breast cancer, when given prior to surgery. Participation in this study could last up to 2.5 months. Conditions: Breast Cancer Intervention / Treatment: DRUG: LY3484356 Location: Germany, Spain, United Kingdom, United States, Belgium, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: BASIC_SCIENCE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Have histologically confirmed invasive ER+, HER2- breast carcinoma * Be willing and able to provide pre- and on-treatment tumor samples * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale * Have adequate organ function * Be able to swallow capsules * Be a postmenopausal woman Exclusion Criteria: * Have bilateral invasive breast cancer * Have metastatic breast cancer * Plan to receive concurrent neoadjuvant therapy with any other non-protocol anti-cancer therapy * Have had prior therapy (of any kind) for an invasive or non-invasive breast cancer * Have had prior radiotherapy to the ipsilateral chest wall for any malignancy * Have had prior anti-estrogen therapy with raloxifene, tamoxifen, aromatase inhibitor, or other selective estrogen receptor modulator (SERM), either for osteoporosis or prevention of breast cancer * Have had prior hormone-replacement therapy within 4 weeks of the start of study treatment * Have had major surgery within 28 days prior to randomization to allow for post-operative healing of the surgical wound and site(s) * Have certain infections such as hepatitis or tuberculosis or HIV that are not well controlled * Have another serious medical condition * Have a history of any other cancer (except nonmelanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years

Study Objectives This randomized phase II trial studies how well docetaxel, oxaliplatin, capecitabine, fluorouracil, and radiation therapy works compared with fluorouracil when given together with oxaliplatin and radiation therapy in treating patients with cancer of the esophagus or gastroesophageal junction that has spread from where it started to nearby tissue or lymph nodes. Drugs used in chemotherapy, such as docetaxel, oxaliplatin, capecitabine, and fluorouracil, 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 dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving more than one drug (combination chemotherapy) together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Conditions: Adenocarcinoma of the Gastroesophageal Junction, Esophageal Cancer, Gastric Cancer Intervention / Treatment: DRUG: capecitabine, DRUG: docetaxel, DRUG: fluorouracil, DRUG: oxaliplatin, RADIATION: radiation therapy, PROCEDURE: therapeutic conventional surgery Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria * Histological confirmation of adenocarcinoma of the esophagus, gastroesophageal (GE) junction, or gastric cardia * Tumor must be considered surgically resectable; Note: patients with T4N0M0 tumors that are potentially resectable are also eligible * Nodal involvement: patients with involvement of celiac nodes, (stations 15-20) are eligible if the primary lesion is mid-thoracic, distal esophagus or GE junction; patients with supraclavicular node involvement are eligible with upper thoracic esophagus primary lesions * Capable of swallowing pills * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 * Absolute neutrophil count (ANC) >= 1500 * Peripheral platelet count >= 100,000 * Hemoglobin >= 9.0 g/dL * Total bilirubin =< 1.5 x upper normal limit (UNL) * Serum glutamic oxaloacetic transaminase (SGOT) (alanine aminotransferase [AST]) =< 3 x UNL * Creatinine =< 1.5 x UNL * Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only * Provide informed written consent * Willingness to return to NCCTG enrolling institution for follow-up * Patient willing to provide mandatory tissue and blood samples for research purposes * Patient willing to allow use of FDG PET/CT scans for mandatory research purposes Exclusion Criteria * Evidence of distant metastases * Palpable supraclavicular nodes, biopsy-proven involvement of supraclavicular nodes, or radiographically involved supraclavicular nodes (> 1.5 cm in greatest dimension) for lesions in mid-thoracic, distal thoracic or GE junction * T1N0M0 or T2N0M0 tumor stage * Any of the following * Pregnant women * Nursing women * Men or women of childbearing potential who are unwilling to employ adequate contraception * Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens * Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive * 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 * Uncontrolled diabetes (i.e., will interfere with the performance of the FDG PET/CT scans) * Receiving current treatment or prior treatment for this malignancy * Other active malignancy 5 years prior to registration, except non-melanotic skin cancer or carcinoma-in-situ of the cervix; if there is a history of prior malignancy, patient must not be receiving other specific treatment (other than hormonal therapy) for cancer * Prior radiation to > 30% of the marrow cavity

Study Objectives The aim of this study is to explore whether FOLFOX6 as treatment could improve the time to progression (TTP) and overall survival (OS) of the patient with recurrent or metastatic esophagus. Conditions: Esophageal Squamous Cell Carcinoma Intervention / Treatment: DRUG: FOLFOX6 Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: SINGLE

Inclusion Criteria: * Histologically proven primary thoracic esophageal squamous cell carcinoma * Without chemotherapy or neo-adjuvant chemotherapy in 6 weeks ,radiotherapy has end at least 1 month,target lesion was not in an irradiated area. * Presence of at least one index lesion measurable by CT scan or MRI * 18~75 years * kps >= 70 * Life expectancy of >= 3 months * ANC >= 2×109/L，PLT >= 100×109/L，Hb >= 90g/L * Cr <= 1.0×UNL * TB <= 1.25×UNL； ALT/AST <= 2.5×UNL，THE patient with liver metastasis ALT/AST <= 5.0×UNL；AKP <= 2.5×UNL * Signed written informed consent Exclusion Criteria: * Previous exposure to oxa therapy in one year * diameter of tumor abdominal >= 10cm, Total volumes of liver lesions >= 50%,lung metastasis >= 25% total lung * chronic diarrhea,enteritis,intestine obstruction which are not under control * Psychiatric or addictive disorders that preclude obtaining informed consent or adherence to protocol. * peripheral neuropathy >= CTCAE 1 * Other serious disease * Previous or concomitant malignancies except non-melanoma skin cancer, carcinoma in situ of the cervix, and invasive carcinoma of the colon, thyroid, cervix, or endometrium treated five years prior to study entry. * USE OTHER ANTITUMOR THERAPY * Breast-feeding or pregnant women, no effective contraception if risk of conception exists

Study Objectives The purpose of this study is to evaluate the addition of Sirolimus (rapamycin) to standard chemotherapy for the treatment of patients with high risk acute myelogenous leukemia (AML). Cancer cells taken from the patients will be studied in the laboratory to see if rapamycin is affecting the mTOR pathway in the cells and if this effect is correlated with how well patients respond to the therapy. Conditions: AML Intervention / Treatment: DRUG: Sirolimus, DRUG: Mitoxantrone, DRUG: Etoposide, DRUG: Cytarabine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must have histologic evidence of high risk acute myeloid leukemia defined as one of the following: 1. Primary refractory non-M3 AML (i) Residual leukemia after a minimum of 2 prior courses of chemotherapy (Same or different) (ii) Evidence of leukemia after a nadir bone marrow biopsy demonstrates no evidence of residual leukemia. 2. Relapsed non-M3 AML 3. Any non-M3 AML age >60 with no evidence of favorable karyotype (stratum 2 ONLY), defined by presence of t(8;21)(q22;q22) [AML1-ETO], inv16(p13;q22), or t(16;16)(p13;q22) [CBF;MYH11] by cytogenetics, FISH, or RT-PCR 4. Secondary AML (from antecedent hematologic malignancy or following therapy with radiation or chemotherapy for another disease) with no evidence of favorable karyotype (stratum 2 ONLY), defined by presence of t(8;21)(q22;q22) [AML1-ETO], inv16(p13;q22), or t(16;16)(p13;q22) [CBF;MYH11] by cytogenetics, FISH, or RT-PCR * Age > or = 18 * ECOG = 0 or 1 Exclusion Criteria: * Subjects with FAB M3 (t(15;17)(q22;q21)[PML-RAR]) are not eligible * Subjects taking the following are not eligible: * Carbamazepine (e.g., Tegretol) * Rifabutin (e.g., Mycobutin) or * Rifampin (e.g., Rifadin) * Rifapentine (e.g., Priftin) * St. John's wort * Clarithromycin (e.g., Biaxin) * Cyclosporine (e.g. Neoral or Sandimmune) * Diltiazem (e.g., Cardizem) * Erythromycin (e.g., Akne-Mycin, Ery-Tab) * Itraconazole (e.g., Sporanox) * Ketoconazole (e.g., Nizoral) * Telithromycin (e.g., Ketek) * Verapamil (e.g., Calan SR, Isoptin, Verelan) * Voriconazole (e.g., VFEND) * Tacrolimus (e.g. Prograf) * Subjects taking fluconazole, voriconazole, itraconazole, posaconazole, and ketoconazole within 72 hours of study entry are not eligible. Reinstitution of fluconazole, voriconazole, itraconazole, posaconazole, ketoconazole and diltiazem is permissible 72 hours after the last dose of sirolimus. * Subjects must not be receiving any chemotherapy agents (except Hydroxyurea). Intrathecal methotrexate and cytarabine are permissible * Subjects must not be receiving growth factors, except for erythropoietin

Study Objectives This study will investigate the efficacy and safety of intrathecal morphine for the patients undergoing robot-assisted prostatectomy Conditions: Prostatic Neoplasms Intervention / Treatment: DRUG: The intravenous patient-controlled analgesia, DRUG: The intrathecal morphine injection 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 for the open nephrectomy Exclusion Criteria: * Patients with renal insufficiency * Patients with coagulopathy * History of any neurologic disorder * History of recent infection in 2 weeks * History of drug abuse * Patients who cannot understand the usage of th intravenous patient-controlled analgesia * Patients using opioids due to the chronic pain

Study Objectives The purpose of this study is to determine if the new ingenol derivative gels are as safe as and as well tolerated as ingenol mebutate gel when applied to AK lesions on the forearm for two consecutive days. Conditions: Actinic Keratosis Intervention / Treatment: DRUG: Ingenol once daily for two consecutive days Location: Australia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: SINGLE_GROUP Masking: SINGLE

Inclusion Criteria: * Must be male or female and at least 18 years of age. * Female patients must be of non-childbearing potential or if of childbearing potential then negative serum and urine pregnancy test and using effective contraception * Ability to provide informed consent Exclusion Criteria: * location of the selected treatment area within 5cm of an incompletely healed wound or within 5cm of a suspected basal cell carcinoma or squamous cell carcinoma * undergone Cosmetic or therapeutic procedures within 2cm of the selected treatment area in the 2 weeks prior to Visit 2 * use of acid-containing therapeutic products within 2cm of the selected treatment area in the 2 weeks prior to Visit 2 * use of topical moisturisers/creams/lotions, artificial tanners or topical steroids within 2cm of the selected treatment areas in the 2 weeks prior to visit 2 Treatment with immunomodulators, or interferon/interferon inducers or systemic medications that suppress the immune system within 4 weeks of Visit 2 * Treatment with 5-FU, imiquimod, diclofenac, or photodynamic therapy within 2 cm of the treatment area in the 8 weeks prior to visit 2 * use of systemic retinoids * those who are currently participating in any other clinical trial * females who are pregnant or are breastfeeding * those known or suspected of not being able to comply with the requirements of the protocol or provide consent

Study Objectives This open-label, multi-center study will evaluate the safety, tolerability, and pharmacokinetics of RO5212054 \[PLX3603\] in participants with BRAF V600-mutated advanced solid tumors. Cohorts of participants will receive escalating oral doses of RO5212054. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs. Conditions: Neoplasms Intervention / Treatment: DRUG: RO5212054 Location: Denmark, Australia, Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Advanced solid tumor * Dose-escalation phase: Histologically confirmed, newly diagnosed or relapsed/ refractory unresectable American Joint Committee on Cancer (AJCC) Stage IIIC or IV disease * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Adequate liver, renal and bone marrow function Exclusion Criteria: * Participants for whom standard therapy exists and is considered appropriate by the investigator * Prior treatment with an inhibitor of BRAF (sorafenib allowed) * Active Central nervous system (CNS) lesions, or history of or known carcinomatous meningitis * Treatment with any chemotherapy, radiotherapy, immunotherapy or investigational agent within 28 days prior to first dose of study drug * Anticipated or ongoing anti-cancer therapies other than those administered in this study * Serious cardiovascular illness within the 6 months prior to study drug administration

Study Objectives Diarrhea is a relatively common complication in patients with cancer. At its inception, several mechanisms participated; malabsorption on the basis of mucositis induced by chemotherapy, dysbiosis induced by broad-spectrum antibiotics and predisposition to infectious diarrhea in immunocompromised patients. Some cytostatics and their metabolites can also induce diarrhea directly due to effect on the intestinal mucosa. Use of probiotics in prevention and treatment of diarrhea relies on both the theoretical assumptions and the results of several clinical trials. Lactic acid bacteria involved in the treatment of dysbiosis, compete for substrate with pathogenic bacteria, produce bacterio-cins, increase transepithelial resistance. Their enzymatic activity affects activation or deactivation of metabolites which cause diarrhea. Production of short chain fatty acids, which are important for the maintenance of intestinal mucosal cells also contributes to their antidiarrhoeal effect. This randomized, double-blind, placebo controlled, multicentre trial was designed to evaluate potential of probiotics to prevent grade 3-4 diarrhea in patients treated by irinotecan based chemotherapy during first 6 weeks of irinotecan based chemotherapy Conditions: Diarrhea, Cancer Intervention / Treatment: DRUG: Probio-Tec® BG-VCap-6.5, DRUG: Placebo Location: Slovakia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * signed written informed consent * age > 18 years * histologically proven colorectal cancer patients starting new line of chemotherapy based on irinotecan * ECOG PS 0 - 1 at study entry * life expectancy more than 3 months * absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; Exclusion Criteria: * impossibility to take oral medication * active infection treated by antibiotic therapy * ileostoma * hypersensitivity to study drug * any concurrent malignancy other than non-melanoma skin cancer, no other cancer in past 5 years. * serious concomitant systemic disorders or diseases incompatible with the study (at the discretion of investigator )

Study Objectives Effects of BAY1002670 on bleeding pattern: non-bleeding rate; on endometrium; on ovarian function; return of menstrual bleeding after treatment; safety and tolerability; PK/PD (pharmacokinetic/pharmacodynamic) relationship Conditions: Leiomyoma Intervention / Treatment: DRUG: BAY1002670, DRUG: Placebo Location: Belgium, United Kingdom, Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Healthy female subjects * Sterilized by tubal ligation * Age 18-45 years * Body mass index (BMI) at screening: >= 18 and <= 32 kg/m² * At least 3 consecutive regular menstrual cycles with a cycle length of 24 - 35 days before first screening examination according to the subject's history * Absence of clinically relevant abnormal findings in the pre-treatment endometrial biopsy Exclusion Criteria: * Regular use of medicines (incl. anabolics) * Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal * Amenorrhea for more than 3 months within the last 6 months before the first screening examination * Lacking suitability for frequent transvaginal ultrasonography (TVU) examinations * Clinically relevant findings (e.g. blood pressure, electrocardiogram [ECG], physical and gynecological examination, laboratory examination)

Study Objectives The Efficacy and safety of Non-anesthesiologist administered propofol (NAAP) for gastrointestinal endoscopy have been widely documented although there is not information which has evaluated the outcomes of colonoscopy it self when the endoscopist has to fulfill the additional task of supervising the sedation. Objective: To determine the equivalence of adenoma detection rate (ADR) in colorectal cancer (CRC) screening colonoscopies performed with NAAP and performed with monitored anesthesia care (MAC). Method: Single blind non-randomized controlled equivalence trial. Patients: Adults between 50 - 69 years old from National CRC screening program (CRCSP). Intervention: The patients are blindly assigned to undergo either colonoscopy with NAAP or MAC according to the arrival of fecal occult blood test, patient's suitability for colonoscopy date and availability of places at endoscopy schedule (with NAAP or MAC). Conditions: Colo-rectal Cancer, Colon Adenoma, ADR Intervention / Treatment: PROCEDURE: Sedation directed by an endoscopist, PROCEDURE: Sedation directed by an anesthesiologist Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: SCREENING Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: Healthy patients - Exclusion Criteria: Patients with familial colorectal cancer history *

Study Objectives Objectives The primary objective is to demonstrate that in patients undergoing major urologic surgery, Patient Controlled Analgesia (PCA) opioid consumption in the first 24 hours after surgery will be significantly less in patients who have had a single shot rectus sheath block pre-operatively in addition to a post-operative rectus sheath continuous block via surgically placed catheter versus those who only have post-operative rectus sheath continuous block. Secondary outcomes will be opioid requirement intra-operatively, Numerical Rating Scale (NRS) pain scores including maximum pain score in Post Anesthesia Care Unit (PACU) and score at 24 and 48 hours, incidence and severity of nausea, number of vomiting episodes, sedation score, time to first bowel movement, time to first mobilization and duration of hospital stay. Conditions: Bladder Neoplasm, Prostate Neoplasm, Pelvic Neoplasm, Urologic Neoplasms, Opioid Use, Anesthesia, Local, Pain, Postoperative Intervention / Treatment: PROCEDURE: Rectus sheath block, PROCEDURE: Bilateral rectus sheath catheter, DRUG: Patient controlled opioid analgesia (PCA), PROCEDURE: Subcutaneous injection saline placebo Location: Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * Adult patients over 18 years * Undergoing major urological surgery * Consent to a rectus sheath blockade as part of their postoperative management Exclusion Criteria: * Patients under 18 years * Local or systemic infection * Patients who refuse consent * Opioid tolerance * History of chronic pain * Psychiatric illness * Allergy to local anesthetic.

Study Objectives This study has been designed to evaluate the efficacy and safety of a 20-mg dose of tadalafil administered "on demand" to patients with erectile dysfunction (ED) after external-beam radiotherapy (EBRT) of prostate cancer. Conditions: Prostate Cancer, Erectile Dysfunction Intervention / Treatment: DRUG: tadalafil Location: Netherlands Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: CROSSOVER Masking: DOUBLE

Inclusion Criteria: * Heterosexual men, at least 18 years of age at Visit 1 and willing to participate in the study. If a qualifying participant has more than one female sexual partner during the study, the participant will not be excluded from the trial. However, the participant will be required to respond to the questionnaires based on the participant's sexual interactions with only one of these partners. * Patients with histologically proven prostate cancer. * Provide signed informed consent. * Developed ED (defined as a consistent change in the quality of erection that adversely affects the patient's satisfaction with sexual intercourse) subsequent to EBRT for prostate cancer. * Patients willing to make on average 1 sexual intercourse attempt every week during the study (including the 4-week run-in period without medication). * Agree not to use any other ED treatment for at least 4 weeks before receiving the initial dose of study drug (ie, during the run-in period and during the treatment phase of the study). * Have been treated by EBRT at least 12 months before screening and were documented to be potent before undergoing EBRT. Exclusion Criteria: * Patients will not be randomized if they did not make at least 1 sexual intercourse attempt during the run-in period. Also patients who are unable to appropriately complete the questionnaires will not be randomized. * ED caused by other primary sexual disorders including premature ejaculation or ED caused by untreated endocrine disease (eg, hypopituitarism, hypothyroidism, or hypogonadism). * History of pelvic surgery (including radical prostatectomy) * Treatment with cancer chemotherapy or anti-androgens. * Have a raising prostate specific antigen level or metastases at Visit 1. * History of penile implant. * The presence of clinically significant penile deformity in the opinion of the investigator. * Evidence of clinically significant renal insufficiency within the last 6 months before Visit 1. * Active symptomatic hepatobiliary disease, including patients with evidence of jaundice at Visit 1. * Patients with chronic stable angina treated with long-acting nitrates, or patients with chronic stable angina who have required short-acting nitrates in the last 90 days, or angina occurring during sexual intercourse in the last 6 months. * Patients having met the criteria for unstable angina (Braunwald, 1989) within 6 months before Visit 1, history of myocardial infarction or coronary artery bypass graft surgery within 90 days before Visit 1, or percutaneous coronary intervention (eg, angioplasty or stent placement) within 90 days before Visit 1. * Any supraventricular arrhythmia with an uncontrolled ventricular response (mean heart rate >100 bpm) at rest despite medical or device therapy, or any history of spontaneous or induced sustained ventricular tachycardia (heart rate >100 bpm for >= 30 sec) despite medical or device therapy, or the presence of an automatic internal cardioverter-defibrillator. * A history of sudden cardiac arrest despite medical or device therapy. * Any evidence of congestive heart failure class 2 or above within 6 months before Visit 1 (Criteria Committee, New York Heart Association, Inc., 1964). * A new, significant conduction defect within 90 days before Visit 1. * Systolic blood pressure >170 or <90 mm Hg or diastolic blood pressure >100 or <50 mm Hg, or patients with a history of malignant hypertension. * History of significant central nervous system injuries (including stroke and spinal cord injury) within the 6 months before Visit 1. * History of HIV infection. * Any condition that would interfere with the patient's ability to provide informed consent or comply with study instructions, would place patient at increased risk, or might confound the interpretation of the study results. * History of drug, alcohol, or substance abuse within the 6 months before Visit 1. * Treatment within the 30 days before Visit 1 with a drug or device that has not received regulatory approval. * Have any condition, limitation, or disease that could, in the judgment of the investigator, preclude evaluation of response to tadalafil.

Study Objectives The purpose of this study is to test the safety and effectiveness of Avastin introduced into the inside of the eyeball in causing shrinkage of the uveal melanoma (tumor of the eye). Avastin is an anti-cancer drug specially designed to shrink blood vessels within tumors. Conditions: Uveal Melanoma Intervention / Treatment: DRUG: AVASTIN Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients diagnosed with large uveal melanomas who elect to undergo enucleation. * Patients diagnosed with uveal melanomas with tumor thickness > 10 mm or basal diameter > 16 mm, as measured by ultrasound examination, funduscopic examination, or transillumination. Exclusion Criteria: * Cases that do not meet the above criteria for tumor size will be ineligible to participate in the study. * Patients with history of metastatic cancer (other than melanoma). * Patients not able to provide consent for the study. * Patients with clinical or radiographic evidence of extraocular extension of the tumor. * Patients with a previous history of an adverse reaction to intravitreal injection. * Patients with a poor view of the fundus due to cataract or vitreous hemorrhage. * Patients with intravitreal silicone oil or gas tamponade. * Patients < 18 years of age. * Women known to be pregnant.

Study Objectives The primary objectives of this study are to determine the acceptance and potential for the effective use of HPV vaccine in the standard and a modified schedule in female sex workers. Secondary objectives include ascertaining the prevalence of HPV types among female sex workers by age and sexual experience. Conditions: Human Papillomavirus Infection Intervention / Treatment: BIOLOGICAL: Gardasil Location: Peru Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Between the age of 18 and 26 years * Registered female sex worker living in Lima * Healthy with no known immune deficiency * Willing to participate in a study of HPV vaccine including a Pap smear, three pregnancy tests, blood draws, and three vaccine administrations over 7 months * Willing to provide informed consent Exclusion Criteria: * Currently pregnant or planning to get pregnant in the next six months * Known immune deficiency disorder * Current receipt of immunosuppressive drugs * Allergy to yeast or known contraindication to HPV vaccine * Women who have had their cervix removed * Previous HPV vaccination * Current fever over 100 degrees Fahrenheit

Study Objectives The purpose of this study is to determine the safety and efficacy of DFP-10917 given via continuous 7 or 14 day infusion to patients with acute leukemias (AML or ALL). Conditions: Acute Myeloid Leukemia, Acute Lymphocytic Leukemia Intervention / Treatment: DRUG: DFP-10917 Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients must have pathologically-confirmed acute leukemia, refractory or relapsed after standard therapy for the disease or for which conventional systemic chemotherapy is not reliably effective or no effective therapy is available Phase II Only: Patient must have histologically or pathologically confirmed diagnosis of AML based on WHO classification that is refractory after standard therapy, or for which conventional systemic chemotherapy is not reliably effective, or no effective therapy is available. Patients aged >= 60 years with newly diagnosed AML who are not eligible for, or who refuse, standard care are also eligible. * Aged >= 18 years. * ECOG Performance Status of 0, 1 or 2. * Adequate clinical laboratory values (i.e., plasma creatinine <= 1.5 x upper limit of normal (ULN) for the institution, bilirubin <=1.5 x ULN, alanine transaminase (ALT) and aspartate transaminase (AST) <= 2.5 x ULN). * Absence of CNS involvement by leukemia. * Absence of uncontrolled intercurrent illnesses, including uncontrolled infections, cardiac conditions, or other organ dysfunctions. * Signed informed consent prior to the start of any study specific procedures. * Women of child-bearing potential must have a negative serum or urine pregnancy test. Male and female patients must agree to use acceptable contraceptive methods for the duration of the study and for at least one month after the last drug administration. Exclusion Criteria: * The interval from prior treatment to time of study drug administration is < 2 weeks for cytotoxic agents or < 5 half-lives for noncytotoxic agents. Exceptions: Use of hydroxyurea is allowed before the start of study and may be administered up to day 5 of the first cycle. * Any >grade 1 persistent clinically significant toxicities from prior chemotherapy. * Extensive prior radiotherapy to more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation. * Any concomitant condition that in the opinion of the investigator could compromise the objectives of this study and the patient's compliance. * A pregnant or lactating woman. * Current malignancies of another type. Exceptions: Patients may participate if they have previously treated and currently controlled prostate cancer, adequately treated in situ cervical cancer and basal cell skin cancer or other malignancies with no evidence of disease for 2 years or more. * Patient has acute promyelocytic leukemia (APL). * Patients with known HIV, HBV or HCV infection (note: testing for these infections is not required). * Documented or known clinically significant bleeding disorder.

Study Objectives The primary objectives are to determine the progression-free survival (PFS) and to evaluate safety of the trastuzumab, bevacizumab and docetaxel regimen. Conditions: Breast Cancer Intervention / Treatment: DRUG: Trastuzumab, DRUG: Bevacizumab, DRUG: Docetaxel Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed breast cancer with evidence of metastatic disease * HER2 3+ or FISH (fluorescent in situ hybridization)+ * Age >= 18 years * No prior trastuzumab, except as given in the adjuvant or neoadjuvant setting. * No prior chemotherapy in the metastatic setting. Exclusion Criteria: * CNS (central nervous system) metastases * Prior radiation therapy within the last 4 weeks * Pregnant (positive pregnancy test) or lactating women * Major surgical procedure, open biopsy, non-healing wounds, or significant traumatic injury within 28 days prior to starting study or anticipation of need for major surgical procedure during the study * Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to start of study.

Study Objectives This multi-center, open-label study will evaluate the safety, pharmacokinetics, pharmacodynamics and efficacy of RO5429083 alone and in combination with cytarabine in patients with acute myelogenous leukemia. In Part A, patients will receive multiple escalating doses of RO5429083 intravenously. In Part B, patients will receive RO5429083 plus up to 4 cycles of cytarabine (1000 mg/m2 iv daily for 5 consecutive days). Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs. Conditions: Myelogenous Leukemia, Acute Intervention / Treatment: DRUG: RO5429083, DRUG: cytarabine Location: Italy, France, Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Adult patients, >= 18 years of age * Histologically or cytologically confirmed, acute myelogenous leukemia (all subtypes except acute promyelotic leukemia) according to WHO criteria * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 * All non-hematological adverse events of any prior chemotherapy, surgery, or radiotherapy must have resolved to NCI-CTC AE Grade < 2, except alopecia * Adequate hepatic and renal function * Patient must be willing to submit blood and bone marrow samples for PK and PD analyses and exploratory biomarkers Exclusion Criteria: * Patients receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy within 14 days of first receipt of study drug, with the exception of hydroxyurea * History of allergic reactions attributed to components of cytarabine and/or the formulated product * Current evidence of CNS leukemia * Increased QTc interval (QTc > 470 ms), baseline resting bradycardia < 45 beats per minute, or baseline resting tachycardia < 100 beats per minute * Family history of long QT syndrome or other risk factors for torsades de pointes, and/or the use of concomitant medications that prolong QT/QTc interval * Uncontrollable intercurrent illness * Pregnant or breast-feeding women * HIV-positive patients receiving anti-retroviral therapy * Patients who refuse to potentially receive blood products and/or have a hypersensitivity to blood products

Study Objectives The study will evaluate how safe and effective abemaciclib is when given to participants whose metastatic prostate cancer progresses after they had received several previous treatments. Conditions: Metastatic Castration-Resistant Prostate Cancer Intervention / Treatment: DRUG: Abemaciclib Location: United States, Spain, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Participant must have metastatic prostate cancer for which castration (medical or surgical) is no longer effective (castration-resistant). * Participant must have disease spread to soft tissue that is measurable. * Participant must have documented evidence of progressive disease by PSA test or imaging. * Participant must have previously received at least one of the following treatment: abiraterone acetate, apalutamide, darolutamide or enzalutamide. * Participant must have previously received chemotherapy with docetaxel and cabazitaxel. * Participant must be willing and amenable to undergo a biopsy of tumor tissue (or able to provide adequate archived tumor tissue sample) and to provide blood for research. * Participant must have good physical functioning ability and adequate organ function. Exclusion Criteria: * Participant must not have received more than 3 therapy regimens for metastatic castration-resistant prostate cancer (NOTE: GnRHa, first-generation antiandrogens (flutamide, nilutamide, or bicalutamide), diethylstilbestrol (DES) (or other estrogens), corticosteroids, ketoconazole, and bone loss-prevention will not count as systemic therapy regimens. * Participants must not have previously received abemaciclib or any cyclin-dependent kinase (CDK)4 and/or CDK6 inhibitors. * Participants must not have serious and/or uncontrolled preexisting medical condition(s) including but not limited to severe renal impairment, severe hepatic impairment, interstitial lung disease (ILD)/pneumonitis, severe dyspnea at rest or requiring oxygen therapy or other serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study. * Participants must not have, or suspected to have, brain metastasis. * Participants must not have untreated spinal cord compression, evidence of spinal metastases with risk of spinal compression or structurally unstable bone lesions suggesting impending fracture.

Study Objectives This study is open to patients with primary HCC who cannot be treated by potentially curative treatment modalities, such as surgical resection, liver transplantation or percutaneous ablation. Patients that satisfy the study eligibility criteria will be randomised in a 1: 1 ratio to receive either Radioembolisation with SIR-Spheres Microspheres or the standardised Transarterial Chemoembolisation procedure. Study Objectives This study will evaluate and compare quality of life as well as safety and efficacy of RE or TACE in patients with unresectable HCC. Patients will be followed for a minimum of 12 months or until death wherever possible in the evaluation of the primary and secondary objectives of this study. Conditions: Hepatocellular Carcinoma Intervention / Treatment: DEVICE: Radioembolisation (SIR-Spheres® microspheres), DRUG: Transarterial Chemoembolisation Location: Spain, Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Male or female patients, aged >= 18 years * Unequivocal diagnosis of primary HCC (confirmed by biopsy/histology or EASL criteria) * Tumour characteristics as follows: * Not more than 5 lesions * If single, maximal diameter <= 10 cm * If multiple, sum of maximal diameters <= 15 cm * Lesions satellite to primary tumour of less than 1 cm in maximal diameter are not included * At least one quantifiable lesion on hepatic MRI * Preserved liver function, corresponding to Child-Pugh class <= B-7 * ECOG performance status <= 2 * Life expectancy >= 12 weeks * Female patients of childbearing potential must have a negative pregnancy test prior to inclusion in the trial and male and female patients must agree to use an effective contraceptive method for the duration of the trial. * Willing and able to provide written informed consent Exclusion Criteria: * Patients expected to undergo surgery (resection or transplantation) within the 24-week period after randomisation. * Ascites, which is detectable on physical examination or clinically symptomatic (but patients having ascites discovered by imaging only should not be excluded). * Serum transaminases > 5 x ULN * Lung shunt > 20% * Extrahepatic disease * Moderate to severe portal hypertension, as evidenced by any of the following criteria (occurring in spite of using common criteria for prophylactic treatment and therapy): * History of variceal haemorrhage in past 2 years * History of hepatic encephalopathy * Platelets < 50.000 /ml * WBC < 3.000 / ml * Previous TIPSS procedure * Portal vein occlusion or hepatofugal flow. * Impaired liver function * Total serum bilirubin > 2.0 mg / dL * Serum albumin < 3.0 g /dl * creatinine > 2 mg / dL * Chemotherapy or other experimental therapy within preceding 4 weeks * Previous TAE / TACE * Previous radiation therapy to liver or lungs * Contraindications for angiography (severe peripheral vascular disease or uncorrectable bleeding diathesis) * Anatomical variants apparent on 99mTc-MAA scan precluding safe administration of RE * Any decompensated concomitant disease * Female patients who are pregnant, breast-feeding, or pre-menopausal and not practising efficient contraceptive method (hormonal contraceptive, intra-uterine device)

Study Objectives * To evaluate the effect of BAY73-4506 on the pharmacokinetics of probe substrates of CYP 2C9 (warfarin), 2C19 (omeprazole) and 3A4 (midazolam) administered in a cocktail approach and on the pharmacokinetics of a probe substrate of CYP 2C8 (rosiglitazone) * To evaluate safety, anti-tumor activity, pharmacokinetics, and pharmacodynamics of BAY73-4506 in patients with advanced solid tumors Conditions: Neoplasms Intervention / Treatment: DRUG: Regorafenib (Stivarga, BAY73-4506), DRUG: Warfarin, DRUG: Omeprazole, DRUG: Midazolam, DRUG: Rosiglitazone Location: Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Female and male subjects must be >= 18 years at the first screening examination / visit * ECOG Performance Status of <= 2 * Histological or cytological documentation of confirmed advanced solid tumors. Subjects should have measurable or non-measurable disease according to RECIST * Life Expectancy of at least 3 months * Adequate bone marrow, liver, and renal functions as assessed by the following laboratory requirements conducted within 14 days prior to the first study treatment: * Hemoglobin >= 9.0 g/dL * Absolute neutrophil count (ANC) >=1,500/mm3 * Platelet count >= 100,000/ mm3 * Total bilirubin <= 1.5 times the upper limit of normal (ULN) * Alkaline phosphatase <= 2 times ULN * ALT and AST <= 2.5 x ULN (<= 5.0 x ULN for subjects with cancer involving the liver) * Serum creatinine <= 1.5 times ULN and glomerular filtration rate (GFR)>= 30 ml/min/1.73 m2, according to the MDRD (Modified Diet in Renal Disease) abbreviated formula * Lipase <= 1.5 ULN * INR and PTT <= 1.5 ULN * Subjects who are therapeutically treated with warfarin, heparin or other anticoagulants are not eligible for study participation in Group A. Subjects who are therapeutically treated with warfarin, heparin or other anticoagulants, will be allowed to participate in Group B of the study provided they meet all eligibility criteria. Close monitoring of at least weekly evaluations will be performed until INR or PTT are stable by the local standard of care. * Recovery from previous drug/procedure-related toxicities to CTC Grade 0 or 1 levels (except for alopecia), or to baseline preceding the prior treatment. Preexisting chemotherapy induced sensory neuropathy of CTC Grade <=2 is not an exclusion criteria. * Negative serum pregnancy test must be obtained within 7 days prior to the start of treatment in women of childbearing potential. Negative results must be available prior to study treatment. * Subjects enrolled in this study must use adequate barrier birth control measures prior to, during the course of the study, and 3 months after the last administration of regorafenib. * An adequate contraception includes the use of condoms or a vasectomy, hormonal contraception with implants or combined PO contraceptives, certain intrauterine devices, bilateral tubal ligation, or hysterectomy. In addition, adequate birth control measures for the subject's partner is required, such as a hormonal contraception with implants or combined PO contraceptives, certain intrauterine devices, bilateral tubal ligation, or hysterectomy, use of condoms or a vasectomy. Exclusion Criteria: * History of cardiac disease: Congestive heart failure (New York Heart Association, NYHA, Class III or IV) or active coronary artery disease (unstable angina [angina symptoms at rest] or new-onset angina [began within the last 3 months] or myocardial infarction within the past 6 months). Treatment with Type 1A or 3 anti-arrhythmics, such as Quinidine, Procainamide, Amiodarone, or Sotalol are not permitted. β-Blockers and digoxin are permitted. * Left ventricular ejection fraction (LVEF) < 50% or below the LLN for the institution (whichever is higher). * Subjects with pheochromocytoma * Dehydration NCI-CTCAE, version 4, Grade > 1 * Uncontrolled hypertension (failure of diastolic blood pressure to fall to or below 90 mmHg or systolic blood pressure to fall to or below 140 mmHg with or without the use of antihypertensive drugs). At screening, subjects with history of hypertension should be on a stable anti-hypertensive treatment for at least 7 days prior to the first dose of study drug. * Patients with known allergy to any of the study drug(s) to be administered, including known severe allergies, non-allergic drug reactions, or multiple drug allergies to any of the study drug(s) to be administered. This is also includes hypersensitivity to any of the compounds or excipients that will be administered to the study subject, specifically regorafenib, and warfarin, omeprazole and midazolam for subjects in Group A, or rosiglitazone for subjects in Group B. * Subjects with arterial or venous thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, or pulmonary embolism within 6 months before the start of study medication.

Study Objectives A Phase 1-2 study of MM-121 in combination with standard therapy for non-small cell lung cancer (NSCLC). Conditions: Carcinoma, Non-Small-Cell Lung Intervention / Treatment: DRUG: MM-121, DRUG: Erlotinib Location: Germany, Canada, Korea, Republic of, Spain, United States, Taiwan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Patients with locally advanced or metastatic non-small cell lung cancer. * Patients must be >= 18 years of age. * Patients must have adequate Performance Status (PS) as measured by ECOG and adequate end organ function. Exclusion Criteria: * Patients with a recent history (within 5 years) of another malignancy. * Patients who are pregnant or nursing. * Patients with clinically significant heart failure. * Patients with clinically significant eye or gastrointestinal abnormalities.

Study Objectives Cervical cancer is one of the leading malignancies affecting women, with 311,000 deaths in 2018, most of them seen in underdeveloped countries. This neoplasm has a pre-invasive state, such as cervical intraepithelial neoplasia (CIN), which is caused by HPV (Human Papillomavirus) infection. The female organism most often is able to eliminate the virus, especially in young patients. However, when the infection becomes persistent, especially for subtypes 16 and 18, the risk of CIN developing an increased. Cytological screening programs can efficiently and wirelessly do this. As high-grade intraepithelial lesions (CIN 2/3) are as demonstrated by worse regression rate, only 13.3% at one year, and higher risk for progression to invasive cancer. As CIN 2/3 need treatment, and as more therapies as they are excisional, which theoretically are better, however, they may compromise the reproductive future of women who are unthreatened, increasing the risk of preterm labor, premature rupture of amniotic membranes, low weight Birth and perinatal mortality. This relationship aroused interest in seeking alternative therapies. Decrease antiviral activity directed against HPV, associated with a higher rate of elimination of the infection. Immediate, an agent that stimulates like dendritic cells to producer cytokines and activates epithelial T cells. Imiquimode, when used in vulvar neoplasias, has been shown to be effective, presenting satisfactory results without treatment of CIN 2/3 of the uterine cervix, requiring a better scientific compilation. Based on these data, this study aims to evaluate the efficacy of topical immunomodulatory treatment for high-grade cervical intraepithelial lesions. Conditions: High Grade Intraepithelial Neoplasia, Cervix Cancer Intervention / Treatment: PROCEDURE: Control, DRUG: Imiquimod Location: Brazil Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * Women between the ages of 25 and 50 with histological diagnosis of CIN 2/3; * Living 300 km or less from the city of Barretos-São Paulo / Brazil. Exclusion Criteria: * Suspected adenocarcinoma (in situ or invasive) or invading squamous cell carcinoma by colposcopy and/or citology; * Being pregnant or breastfeeding; * Women with some immunodeficiency or transplanted; * Previous treatment history for CIN 2/3.

Study Objectives To see if it is possible to use short-duration tacrolimus after a peripheral blood stem cell transplant in certain malignancies that are considered difficult to engraft. Conditions: Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, Small Lymphocytic Lymphoma, Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Chronic Myeloid Leukemia, Chronic Myeloproliferative Disorders, Multiple Myeloma, Plasma Cell Neoplasm, Plasma Cell Dyscrasia, Myelofibrosis, Polycythemia Vera, Essential Thrombocythemia, Plasma Cell Leukemia Intervention / Treatment: DRUG: Fludarabine, DRUG: Cyclophosphamide, RADIATION: Total body irradiation, DRUG: Tacrolimus, DRUG: Mycophenolate mofetil Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Presence of a suitable related HLA-haploidentical or -matched stem cell donor, or a 10/10 matched unrelated donor * Eligible diagnoses: myelodysplastic syndrome (MDS) with at least 1 poor-risk feature; small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL) with 17p deletion or with progression < 6 months after a second or greater treatment regimen; T-cell prolymphocytic leukemia (PLL) in partial response or better; interferon- or tyrosine-kinase-refractory chronic myeloid leukemia (CML), or CML in second or subsequent chronic phase; Philadelphia chromosome negative (Ph-) myeloproliferative disease, including myelofibrosis; Multiple myeloma or plasma cell leukemia in partial response or better; Hematologic malignancy in complete remission with minimal residual disease (MRD) detectable by conventional cytogenetics, FISH, flow cytometry, or molecular testing * Any previous autologous transplant must have occurred > 3 months ago * Left ventricular ejection fraction (LVEF) >= 35%, or shortening fraction > 25% * Bilirubin <= 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis) * AST and ALT <= 5 x institutional upper limit of normal * FEV1 and FVC >= 40% of predicted; if unable to perform pulmonary function testing, oxygen saturation > 92% on room air * ECOG performance status <= 2, or Karnofsky/Lansky status >= 60 Exclusion Criteria: * Pregnancy or active breastfeeding * Uncontrolled active infection * Previous allogeneic transplant * Active extramedullary leukemia or active central nervous system (CNS) malignant disease

Study Objectives Nab-paclitaxel (interchangeable with ABRAXANE and ABI-007) is a unique protein formulation of a noncrystalline, amorphous form of paclitaxel in an insoluble particle state. Nab-paclitaxel was designed to improve the chemotherapeutic effects of paclitaxel by exploiting endogenous transport pathways to deliver higher doses of paclitaxel to the tumor and to reduce the solvent-related hypersensitivity and other toxicities associated with Taxol® (paclitaxel) injections, the solvent Cremophor EL, and ethanol vehicle. Nab-paclitaxel provides more rapid tissue distribution and increased tumor accumulation compared to cremophor-EL paclitaxel. Mechanistically, albumin receptor-mediated transport across the endothelium, binding to interstitial proteins, and macropinocytic or receptor-mediated uptake into tumor cells as well as sequestration of paclitaxel by cremophor-EL may contribute to the observed differences. Furthermore, nab-paclitaxel synergizes with gemcitabine in preclinical models. The Cremophor EL-free medium enables nab-paclitaxel to be given at a higher dose and in a shorter duration without the need for premedication to prevent solvent-related hypersensitivity reactions. As of March 2014, nab-paclitaxel is approved under the trade name of ABRAXANE in over 45 countries/regions, including the US, Canada, India, European Union/European Economic Area, South Korea, China, Australia, Bhutan, United Arab Emirates, Nepal, New Zealand, Japan, Russia, Sri Lanka, Argentina, Hong Kong, and Lebanon for the treatment of patients with metastatic breast cancer. ABRAXANE is also approved for the first-line treatment of locally advanced or metastatic non small cell lung cancer (NSCLC) in the US, Japan, Argentina, Australia, and New Zealand, for treatment of advanced gastric cancer in Japan, and for first-line treatment of metastatic adenocarcinoma of the pancreas in the US, EU/EEA, Australia, New Zealand and Argentina. Conditions: Pancreatic Ductal Adenocarcinoma Intervention / Treatment: DRUG: nab-paclitaxel, DRUG: gemcitabine Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma (Islet cell neoplasms or neuroendocrine carcinomas are excluded) * >= 18 years of age at the time of signing the informed consent document * ECOG 0-1 * At least one measurable lesion according to recist v1.1 * No prior palliative chemotherapy for the treatment of metastatic pancreatic cancer (Prior treatment with 5-FU or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed if the treatment had been received at least 6 months before enroll). * Adequate BM function: ANC >=1.5 × 109/L; Platelet count >=100,000/mm2 (100 × 109/L); Hb (Hb) >=9 g/dL. * Adequate liver and renal function (obtained <=14 days prior to enroll): AST (SGOT), ALT (SGPT) <=2.5 × upper limit of normal range (ULN), unless liver metastases are clearly present, then <=5 × ULN is allowed; Total bilirubin 1.5 <= ULN; Serum creatinine within normal limits or calculated clearance >= 60 mL/min/1.73 m2 * Albumin level >= 3 g/dl * Subjects should be asymptomatic for jaundice prior to Cycle 1 Day 1 * Subject with signed the Informed Consent Form (ICF) prior to participation in any study-related activities. * Female of childbearing potential (FCBP) (defined as a sexually mature woman who (1) has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or (2) has not been naturally postmenopausal for at least 24 consecutive months [ie, has had menses at any time during the preceding 24 consecutive months]) must: * Either commit to true abstinence or agree to the use of 2 physician-approved contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on IP; and for 3 months following the last dose of IP; and * Has a negative serum pregnancy test (β-hCG) result at screening * Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for 6 months following IP discontinuation, even if he has undergone a successful vasectomy * Subject able to adhere to the study visit schedule and other protocol requirements. Exclusion Criteria: * Subject has known symptomatic brain metastases. * History of malignancy in the last 5 years. * Breast-feeding or pregnant female * Patients with plastic biliary stent (Metal biliary stents are allowed.) * Subject has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy. * Subject has known historical or active infection with HIV, hepatitis B, or hepatitis C. * Subject has undergone major surgery within 4 weeks prior to Cycle 1 Day 1 of treatment in this study. * Subject who experienced a recent myocardial infarction, including severe/unstable angina pectoris, coronary/peripheral artery bypass graft, uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG) abnormality, significant or uncontrolled cardiovascular disease CHF, and cerebrovascular accident or transient ischemic attack, or seizure disorder in the past year. * Subject has a history of allergy or hypersensitivity to any of the study drugs * Subjects with history of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa). * Subjects with a history of interstitial lung disease * Any other malignancy within 5 years prior to enrollment, with the exception of adequately treated in-situ carcinoma of the prostate (Gleason score <= 7), cervix, uteri, or nonmelanomatous skin cancer (all treatment of which should have been completed 6 months prior to enrollment). * Patients has > Grade 1 pre-existing peripheral neuropathy (per CTCAE) * Subject has serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, which could compromise the subject's safety or the study data integrity. * Subject is enrolled in any other clinical protocol or investigational trial with an interventional agent or assessments that may interfere with study procedures. * Subject is unwilling or unable to comply with study procedures * Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.

Study Objectives Malignant ascites represents a severe clinical problem for physicians and patients being confronted with this common symptom of advanced-stage gastrointestinal cancer. Unfortunately, there is no standardized and evidence-based treatment for malignant ascites and therapies which are commonly being used are only temporarily effective. Newer modes of therapy, such as the application of the tri-functional antibody catumaxomab, are associated with significant side effects and are limited to patients in stages of good overall performance. Therefore, there is still an urgent need for more effective, longer-lasting, and less toxic modes of treatment for peritoneal effusions caused by gastrointestinal cancers. Preclinical data strongly suggest that bevacizumab might be a very effective agent for the treatment of malignant ascites, which is in large part caused by the hyperpermeability-promoting factor VEGF. Emerging clinical results from cancer patients with malignant ascites treated with bevacizumab add further support to this idea. Bevacizumab has been tested in a variety of large clinical trials, has a good toxicity profile, and is effective in a number of human cancers underlying malignant ascites. In the present study, Bevacizumab will be administered as an intraperitoneal infusion at an absolute standardized dosage of 400 mg. This dosage was chosen because it is comparable to the approved standard dosage for intravenous administration which was also used in both studies reporting the successful and safe intraperitoneal administration of Bevacizumab to patients with malignant ascites. Finally, a standardized dosage seems more practical in the particular patient population treated in this study. Conditions: Malignant Ascites, Gastrointestinal Cancers Intervention / Treatment: DRUG: Bevacizumab, OTHER: Placebo Location: Germany Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * Age >= 18 years * Written informed consent has been obtained prior to inclu¬sion into the study * Patient is capable and willing to comply with the study * Histologically confirmed esophageal, gastric, pancreatic, cholangiocellular, hepatocellular, or colorectal carcinoma * Cytologically confirmed ascites OR diagnosis of an exsudate (total protein in ascites > 30 g/l) clinically suggestive for malignant ascites OR morphological diagnosis of peritoneal carcinosis by CT , MRT or ultrasound * Ascites clinically judged as not responsive to conventional systemic therapies for primary malignancy * Ascites clinically judged as not responsive to diuretics * At the time of inclusion paracentesis required at least twice within past 4 weeks. * Before inclusion of the patient into the study, a 4-week screening period will allow for a stringent evaluation of the patient regarding fulfillment of inclusion and exclusion criteria. Importantly, no treatments for malignant ascites other than paracentesis and diuretics are allowed during the 4-week screening period. * ECOG performance score 0-3 * Life expectancy > 12 weeks * Laboratory parameters: Hematology * Neutrophils > 1,500/µl * Platelets > 100,000/µl * Hemoglobin >= 9 g/dl or 5.59 mmol/l Hemastasiology * INR <= 1.5 x ULN and aPTT <= 1.5 x ULN within past 7 dClinical chemistry * Creatinine clearance > 30 ml/min, serum creatinine < 2.5 x ULN * Serum bilirubin < 3.0 x ULN * Alkaline phosphatase and transaminases < 3.0 x ULN (in case of liver metastases < 7 x ULN) Urinalysis: * Patients with < 2+ proteinuria on dipstick urinalysis. * Patients with >= 2+ proteinuria on dipstick urinalysis, who demonstrate < 2.0 g of protein/24 h on 24-h urine collection Exclusion Criteria: * Concomitant malignancies other than gastrointestinal cancers (Patients with curatively treated basal and squamous cell carcino¬ma of the skin and / or in-situ carci¬noma of the cervix are eli¬gible). * Bacterial peritonitis as indicated by laboratory results (neutrophil count > 250 / µl ascites) or clinical suspicion * Hemorrhagic ascites (ascites hematocrit > 2%) * Transudative ascites (total protein in ascites < 30 g/l) * Parallel treatment with anti-tumor agents other than the study medication from inclusion into the study until safety follow-up. Chemotherapy may be continued if started before screening phase (- 4 weeks before inclusion). Parallel Treatment with Bevacizumab i.v. is not allowed. * Therapy naïve patients * Parallel treatment of ascites with measures other than para¬centesis, diuretics, and the study drugs from 4 weeks before inclusion into the study until safety follow-up. * Patients with extensive metastases of the liver making up > 70% of the total liver mass * Child C cirrhosis of the liver * Occlusion or thrombosis of the portal vein. * Evidence of current and symptomatic central nervous system (CNS) metas¬ta¬ses or spinal cord compression. * Clinically significant cardiovascular diseases, e.g., un¬con¬trolled hypertension, uncontrolled arrhythmia, hemoptoe, cardiovascular accident within the last 6 months before treatment start, unstable angina, congestive heart failure (CHF) NYHA grade III/IV, symptomatic coronary heart disease, peripheral arterial disease stage >= II. * History of fistula formation involving an internal organ (e.g. tracheo-oesophagal, bronchopleural, biliary, vagina and bladder) * Major surgical procedure, open biopsy, or significant trau¬matic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study. * Concomitant treatment with intravenous Bevacizumab for primary malignancy from inclusion into study until safety follow-up. Prior treatment with Bevacizumab for primary malignancy is not exclusionary. * Serious non-healing wound, ulcer or bone fracture. * Radiotherapy for purposes other than local control of symp¬toms. * Evidence of bleeding diathesis or coagulopathy. * Hematopoietic diseases. * Known intra-abdominal inflammatory process or serious gastrointestinal ulceration. * History of chronic intestinal diseases associated with severe diarrhea. * Thrombo-embolic events or severe hemorrhage (<= 6 months before treatment start). * Known hypersensitivity to the test drug Bevacizumab * Evidence of any other disease, metabolic dysfunction, physi¬cal examination finding, or laboratory finding giving reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug or puts the patient at high risk for treatment-related compli¬cations. * With the only exception of full dose (INR > 1.5) oral coumarin-derived anticoagulants, the use of full dose anticoagulants is allowed as long as the INR or a PTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for at least two weeks at the time of randomisation. * Patients who participated within the last 30 days prior to enrolment in a clinical trial and received a non approved investigational drug (e.g. follow up within the trial is not exclusionary). * Patients who have participated in this study before. * Women, lactating, pregnant or of childbearing potential and fertile men not using a highly effective contraceptive method . [Women of childbearing potential must have a negative pregnancy test (serum ß HCG) within 7 days before the first dose of study drug]. * Patients who are committed to an institution by virtue of an order issued either by the judicial or the administra¬tive authorities (according to § 40 (1) 4 AMG). * Patients who are underage or patients who are incapable to understand the aim, importance and consequences of the study and to give legal informed consent (according to § 40 (4) and § 41 (2) and (3) AMG). * Patients with a history of a psychological illness or con¬di¬tion such as to interfere with the patient's ability to un¬der¬stand the requirements of the study. * Patients who possibly are dependent on the sponsor or investigator.

Study Objectives Rituximab is an antibody made in a laboratory. It binds to lymphoma cells and kills them. Treatment of recurrent B-cell lymphoma with rituximab may delay or prevent relapses. A total of 166 patients with recurrent B-cell lymphoma were given intravenous rituximab once a week for 4 weeks. The patients' tumors were measured before and after treatment. Ten patients had a complete response and 70 patients had a partial response to rituximab. The median duration of response was 11.2 months. Conditions: Low-Grade or Follicular B-Cell Non-Hodgkin's Lymphoma Intervention / Treatment: DRUG: rituximab Location: United States, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Diagnosis of relapsed, low-grade or follicular B-cell lymphoma * CD20-positive lymphoma * Progressive, measurable disease * Sign informed consent * 3 weeks beyond standard therapy * Good performance status * Adequate hematologic, renal, and hepatic function Exclusion Criteria: * Chronic lymphocytic leukemia * Lesions greater than or equal to 10 cm in diameter * CNS lymphoma * AIDS-related lymphoma * Pleural effusions or ascites secondary to lymphoma * Active, opportunistic infection * Serious nonmalignant disease * Prior investigational therapies, including prior anti-CD20 therapy * Recent major surgery

Study Objectives This is an open-label trial to estimate the concentrations of brentuximab vedotin in relapsed/refractory Hodgkin lymphoma (HL) or relapsed/refractory systemic anaplastic large cell lymphoma (sALCL) participants treated with either brentuximab vedotin or brentuximab vedotin + rifampicin. Conditions: Hodgkin Lymphoma, Anaplastic Large-cell Lymphoma Intervention / Treatment: DRUG: brentuximab vedotin, DRUG: Brentuximab vedotin and rifampicin Location: Belgium, Lithuania, Spain Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Male or female participants between 18 years and 75 years old, with relapsed or refractory HL or relapsed or refractory sALCL who have previously received at least 1 multiagent chemotherapy * Measurable disease * An Eastern Cooperative Oncology Group (ECOG) performance of 0 or 1 * Female participants who are postmenopausal for at least 1 year before the screening visit, surgically sterile, or agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 30 days after the last dose of study drug, or agree to practice true abstinence * Male participants who agree to practice effective barrier contraception during the entire study treatment period through 6 months after the last dose of study drug or agree to practice true abstinence * Clinical laboratory values as specified in the study protocol Exclusion Criteria: * Participants for whom rifampicin is contraindicated * Previously received an allogeneic transplant. * Participants with current diagnosis of primary cutaneous anaplastic large cell lymphoma (ALCL) (participants whose ALCL has transformed to sALCL are eligible). * Known cerebral/meningeal disease including signs or symptoms of progressive multifocal leukoencephalopathy (PML) * Female participants who are lactating and breastfeeding or pregnant * Known human immunodeficiency virus (HIV) positive, * Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection

Study Objectives The purpose of this study is to assess the safety profile of brentuximab vedotin sequentially and in combination with multi-agent chemotherapy in front-line treatment for CD30-positive mature T-cell and NK-cell neoplasms, including systemic anaplastic large cell lymphoma. It is a phase 1, open-label, dose escalation study in three arms designed to define the MTD, PK, immunogenicity, and anti-tumor activity of brentuximab vedotin in sequence and in combination with multi-agent front-line chemotherapy. Conditions: Lymphoma, Large-Cell, Anaplastic, Lymphoma, NK-cell, Lymphoma, T-cell Intervention / Treatment: DRUG: brentuximab vedotin, DRUG: cyclophosphamide, DRUG: brentuximab vedotin, DRUG: prednisone, DRUG: cyclophosphamide, DRUG: doxorubicin, DRUG: doxorubicin, DRUG: prednisone, DRUG: vincristine Location: United States, 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: * Treatment-naive CD30-positive mature T-cell and NK-cell neoplasms, including systemic anaplastic large cell lymphoma * Measurable disease of at least 1.5 cm * ECOG performance status less than or equal to 2 Exclusion Criteria: * Known cerebral/meningeal disease, including history of progressive multifocal leukoencephalopathy * Current diagnosis of primary cutaneous anaplastic large cell lymphoma, mycosis fungoides, Sezary syndrome or other primary cutaneous lymphomas; extranodal NK/T-cell lymphoma, nasal type * History of another primary malignancy that has not been in remission for at least 3 years * Left ventricular ejection fraction <45% or symptomatic cardiac disease, or myocardial infarction within the past 12 months * Viral, bacterial, or fungal infection within two weeks prior to the first dose of brentuximab vedotin * Known human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus positive status

Study Objectives The primary objective: -To assess the efficacy of TCH and TCHL in neo-adjuvant treatment of HER-2 positive breast cancer, using pathological complete response (pCR) as the primary endpoint (Phase II). Secondary objectives: * To assess the clinical response rate and overall response rate for docetaxel and carboplatin with trastuzumab alone or trastuzumab combined with lapatinib in HER-2 positive breast cancer. * To assess the relationship between drug exposure and adverse events. * To examine potential molecular and pharmacological markers of response to trastuzumab and lapatinib * To assess Disease-free Survival (DFS) and Overall Survival (OS) * To determine if prophylactic Loperamide significantly reduces the number of diarrhoea -related adverse events. Conditions: Breast Cancer Intervention / Treatment: DRUG: Docetaxel, Carboplatin and Trastuzumab, DRUG: Docetaxel, Carboplatin, Trastuzumab and Lapatinib Location: Ireland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Written informed consent obtained prior to any study-related procedures * Age > 18 years * Histologically proven breast cancer, for which neo-adjuvant chemotherapy and trastuzumab is considered a valid therapeutic strategy. * Patients with the following TNM stages (refer to AJCC 7th Edition - Appendix M) of breast cancer are eligible: * T2, T3, T4a, T4b, T4c, T4d which is node negative or node positive (histologically or cytologically confirmed) or * Any T with lymph node positive disease (histologically or cytologically confirmed) * Patients with multifocal tumours are not excluded; T stage assignment must be based on the largest tumour. * Patients presenting with bilateral breast cancer are not eligible * Tumour HER2/neu positive (3+ by IHC or fluorescence in situ hybridization (FISH) positive) * Oestrogen and progesterone receptor status known prior to study entry * ECOG performance status score < or equal to 1 * Cardiac ejection fraction >= 50% as measured by echocardiogram or MUGA scan within 3 months prior to randomisation. Note that baseline and on treatment scans should be performed using the same modality and preferably at the same institution * The effects of lapatinib on the developing human foetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (non-hormonal or barrier method of birth control, abstinence or a vasectomy partner) 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. -If applicable, post-menopausal status will be defined as patients who are amenorrheic for > 1 year or for a shorter duration if FSH, LH and/or oestradiol levels are within the post-menopausal range * Patient is accessible and willing to comply with treatment, tissue acquisition and follow up. * Formalin-fixed paraffin-embedded tissue available from diagnostic biopsy and/or definitive surgical intervention -Where possible fresh frozen tissue will be sought as outlined per protocol. * Adequate bone marrow function within 14 days prior to randomisation as defined by the following laboratory values 1. Absolute neutrophil count >= 1.0 x 10^9/L 2. Haemoglobin >= 9.0 g/dL 3. Platelet count >= 100 x 10^9/L * Adequate renal function within 14 days prior to randomisation as defined by: 1. Serum creatinine < or equal to 1.25 x upper limit of normal (ULN), defined by institution 2. Serum creatinine clearance of > 60 mg/ml/min * Adequate hepatic function within 14 days prior to randomisation as defined by: 1. Total bilirubin < or equal to 1.0 x upper limit of normal (ULN). Patients with Gilbert's syndrome prior to study entry must have total bilirubin <3X ULN. 2. Alkaline phosphatase and AST/ALT within parameters specified by protocol. * Able to swallow and retain oral medication * Patients must be deemed potentially operable following neo-adjuvant treatment. Exclusion Criteria: * Prior therapy with systemic cytotoxic chemotherapy Lapatinib or Trastuzumab. * Prior taxanes * Radiotherapy (Except for radiotherapy localised to radiotherapy to a primary squamous or basal cell skin cancer). * Patients with metastatic disease (M1). * Concurrent therapy with any other non-protocol anti-cancer therapy * History of any other malignancy within the past 5 years, with the exception of non-melanoma skin cancer, in situ carcinoma of the breast (ductal or lobular) or carcinoma-in-situ of the cervix. * Current therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective oestrogen receptor modulators (SERMs), either for osteoporosis or prevention of breast cancer. Patients must have discontinued these agents 14 days prior to enrolment. * Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment must be stopped prior to enrolment. * Pre-existing motor or sensory neurotoxicity of a severity >= Grade 2 by NCI-CTCAE version 4.0. * Poorly controlled hypertension (e.g. systolic >180mm Hg or diastolic >100mm Hg.) * Any history of myocardial infarction, angina pectoris or congestive heart failure. Patients on current therapy for arrythmias are excluded. For other patients with a history of self-limiting cardiac dieases (e.g. pericarditis, temporary secondary arrythmias) more than 1 year must have past prior to enrolment on the study * Inflammatory bowel disease or other bowel condition causing chronic diarrhoea, requiring active therapy. * Active, uncontrolled infection requiring parenteral antimicrobials or any condition requiring maintenance therapeutic (i.e. non-replacement) doses of corticosteroids. * The presence of any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of the drugs in this protocol or place the patient at undue risk for treatment complications * Male patients. * Patients with known hypersensitivity to Chinese hamster ovary products or other recombinant human or humanized antibodies and/or known hypersensitivity to any of the study drugs or their ingredients (eg, polysorbate 80 in docetaxel) * Pregnant women are excluded from this study because lapatinib is member of the 4-anilinoquinazoline class of kinase inhibitors with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lapatinib, breastfeeding should be discontinued if the mother is treated with lapatinib * HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with lapatinib. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated. * Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis). * Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors as defined in Table 2. * Have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)

Study Objectives The purpose of this study is to evaluate the efficacy of Pixantrone + Rituximab compared to Gemcitabine + Rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), or follicular grade 3 lymphoma. Conditions: Diffuse Large B-cell Lymphoma, de Novo DLBCL, DLBCL Transformed From Indolent Lymphoma, Follicular Grade 3 Lymphoma Intervention / Treatment: DRUG: Pixantrone + Rituximab, DRUG: Gemcitabine + Rituximab Location: Bulgaria, Hungary, Germany, Italy, Spain, Romania, Ukraine, Denmark, United States, Belgium, Slovakia, United Kingdom, Austria, Czechia, Russian Federation, France, Poland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: SINGLE

Inclusion Criteria: * Diagnosis of DLBCL (de novo DLBCL, or transformed from indolent lymphoma) or follicular grade 3 lymphoma on the basis of tissue biopsy. * Patients with de novo DLBCL must have received 1-3 treatment regimens for DLBCL. Patients with follicular grade 3 lymphoma must have received 1-3 treatment regimens for follicular lymphoma (any grade). Patients with DLBCL transformed from indolent lymphoma must have received at least 1-4 treatment regimens for NHL. * Received rituximab containing a multi-agent therapy for the treatment of NHL. * Not eligible for high-dose chemotherapy and stem cell transplant. * Patients with DLBCL transformed from indolent lymphoma must have had a complete or partial response to a therapy for NHL lasting at least 12 weeks. Exclusion Criteria: * Primary refractory de novo DLBCL or primary refractory follicular grade 3 lymphoma, defined as documented progression within 12 weeks of the last cycle of the first-line multi-agent regimen. * Prior treatment with cumulative dose of doxorubicin or equivalent exceeding 450 mg/m2 * Any experimental therapy <= 28 days prior to randomization * Other malignancy within last 5 years except for the following: curatively treated basal cell/squamous cell skin cancer, carcinoma in situ of the cervix, superficial transitional cell bladder carcinoma, or in situ ductal carcinoma of the breast after complete resection * Any contraindication or known allergy or hypersensitivity to any study drugs * Concomitant therapy with any anticancer agents, immunosuppressive agents, other investigational anticancer therapies. Low-dose corticosteroids for the treatment of non cancer-related illnesses are permitted.

Study Objectives Gemcitabine is a novel analog of the nucleoside deoxycytidine that acts via inhibition of DNA synthesis.Docetaxel is a semisynthetic taxane and promotes microtubule assembly and inhibits microtubule depolymerization. In this study, patients received gemcitabine 900 mg/m2 on days 1 and 8 plus docetaxel 100 mg/m2 on day 8 with G-CSF support every 3 week. Conditions: Metastatic Carcinoma, Recurrent Esophageal Squamous Cell Carcinoma Intervention / Treatment: DRUG: Gemcitabine/Docetaxel Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically confirmed metastatic, or recurrent esophageal squamous cell carcinoma * Age > 18 years * ECOG performance status 0 - 2 * At least one measurable lesion(s) by RECIST 1.1 criteria * Life expectancy >= 3 months * At least one cytotoxic chemotherapy regimen (adjuvant chemotherapy will be considered as one regimen if administered within 6 months from the date of study entry) (upto three prior regimens will be allowed) * Prior radiotherapy must be completed 2 weeks before study entry. * Adequate bone marrow function (>= ANC 1,500/ul, >= platelet 100,000/ul, >= Hemoglobin 9.0 g/dl) * Adequate renal function (<= serum creatinine 1.5 mg/dl or CCr >= 50 ml/min) * Adequate liver function (<= serum bilirubin 1.5 mg/dl, <= AST/ALT x 3 upper normal limit) * Written informed consent Exclusion Criteria: * Evidence of serious gastrointestinal bleeding * Serious pulmonary conditions/illness (e.g. chronic lung disease with hypoxemia) * Serious metabolic disease such as severe non-compensated diabetes mellitus * History of significant neurologic or psychiatric disorders * Serious uncontrolled intercurrent infections, or other serious uncontrolled concomitant disease * Pregnant or lactating woman

Study Objectives The purpose of this study is to assess the safety and efficacy of Timolol 0.25% and 0.5% doses. Conditions: Infantile Hemangioma Intervention / Treatment: DRUG: 0.25% Timolol Maleate Gel Forming Solution, DRUG: 0.5% Timolol Maleate Gel Forming Solution Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria * Documented informed consent from legal guardian * 0-84 days postnatal age at time of first study dose or when enrolled into the non-intervention cohort. * Clinical diagnosis of superficial cutaneous or mucosal infantile hemangioma (must include all of the following): 1. Superficial lesion in the dermis 2. Thin <2 mm in thickness 3. Small >=5 cm at its longest dimension and <=10cm2 4. Involves skin or keratinized mucosa Exclusion Criteria * History of previous treatment with any pharmacologic or laser therapy for IH * Ongoing therapy with an oral beta blocker or oral corticosteroid (e.g., cardiac arrhythmia, adrenal insufficiency, upper airway obstruction, tetralogy of fallot (TOF), hypertension, reactive airways disease) * IH that requires systemic therapy (defined by dynamic complication scale >3) * IH of the non-keratinized mucosa * Infants with more than one hemangioma that requires therapy * Hemodynamically significant cardiovascular disease, as determined by the investigator * Known allergy to beta blockers or vehicle * Heart rate <100 beats per minute at screening visit * Known prenatal or postnatal diagnosis of 2nd/3rd degree atrioventricular block * History of Reactive Airways Disease (RAD) * Any condition which would make the participant, in the opinion of the investigator unsuitable for the study.

Study Objectives The purpose of this research study is to find the answers to the following questions: 1. What are the highest doses of CBP501 and cisplatin that can be safely administered as consecutive 2-hours and 1-hour infusions every 21 days? 2. What are the side effects of the combination of CBP501 and cisplatin when given as an infusion every 21 days? 3. What amount of CBP501 and cisplatin are found in the blood at certain times after it is given? 4. Are there any substances in your blood or tumor that can tell us about tumor sensitivity to CBP501 and cisplatin? 5. Will CBP501 given with cisplatin help to treat your cancer? Conditions: Cancer, Solid Tumors Intervention / Treatment: DRUG: CBP501 and 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: * Signed informed consent obtained prior to initiation of any study-specific procedures. * Pathologically-confirmed, locally advanced or metastatic solid tumors, refractory to standard therapy. * Male or female patients aged 18 years or over. * ECOG Performance Status (PS): 0-1. * Life expectancy > 3 months. * Previous anticancer treatment must be discontinued at least 3 weeks prior to first dose of study treatment (6 weeks for mitomycin C; 6 weeks for anti-androgen therapy if discontinued prior to treatment initiation, with the exception of 8 weeks for bicalutamide). * Adequate organ function including the following: * Bone Marrow: absolute neutrophil count (ANC) ³ 1.5 x 109/L, platelet count ³ 100 x 109/L, hemoglobin ³ 9 g/dL * Hepatic: Bilirubin £ 1.5 x the upper limit of normal (ULN), aspartate transaminases (AST/SGOT) and alanine transaminases (ALT/SGPT) £ 2.5 x ULN (or <= 5 x ULN if liver metastases are present), INR £ 1.5 x ULN * Renal: Serum creatinine <= 1.5 mg/dL or creatinine clearance ³ 70 mL/min (calculated according to the Cockroft and Gault formula) * Metabolic: serum potassium, calcium and magnesium ³ lower limit of normal (LLN) * Creatine phosphokinase isoenzymes: CPK-MB, CPK-MM <= ULN * Troponin I serum level within normal values * Female patients of child-bearing potential must have a negative pregnancy test and use at least one form of contraception as approved by the investigator for 4 weeks prior to the study and 4 months after the last dose of study drug. For the purposes of this study, child-bearing potential is defined as: "All female patients unless they are post-menopausal for at least one year or are surgically sterile". * Male patients must use a form of barrier contraception approved by the investigator during the study and for 4 months after the last dose of study drug. * Ability to co-operate with the treatment and follow-up. Exclusion Criteria: * Radiation therapy to more than 30% of the bone marrow prior to entry into the study. * Prior chemotherapy with nitrosoureas or high dose carboplatin (AUC > 6 mg/mL), prior mitomycin C cumulative dose ³ 25 mg/m², prior bone marrow transplant or intensive chemotherapy with stem cell support. * Presence of any serious concomitant systemic disorders incompatible with the study (e.g. uncontrolled congestive heart failure, active infection, etc.). * Any previous history of another malignancy (other than cured basal cell carcinoma of the skin or cured in-situ carcinoma of the cervix) within 5 years of study entry. * Presence of any significant central nervous system or psychiatric disorder(s) that would hamper the patient's compliance. * Evidence of peripheral neuropathy > grade 1 according to NCI-CTCAE Version 3. * Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to study entry. * Pregnant or breast-feeding patients or any patient with childbearing potential not using adequate contraception. * Known HIV, HBV, HCV infection. * Active CNS metastasis: patients with a history of CNS metastases will be eligible if they have been treated and are stable without symptoms for 4 weeks after completion of treatment, with image documentation required, and must be either off steroids or on a stable dose of steroids for > 1 week prior to enrollment.

Study Objectives This is a phase II window study of the combination of ZD1839 (gefitinib) and irinotecan in children with high-risk neuroblastoma followed by standard induction chemotherapy, intensification with autologous stem cell transplantation, and an oral maintenance phase with 13-cis-retinoic acid and topotecan. We hypothesize that the ZD1839 (gefitinib) and irinotecan window will be efficacious. Conditions: Neuroblastoma Intervention / Treatment: DRUG: Gefitinib, Irinotecan, Cycophosphamide, Doxorubicin, Etoposide, Cisplatin, Topotecan, Carboplatin, Melphalan, 13-cis retinoic acid, PROCEDURE: Radiation therapy, Surgery, Peripheral Stem cell transplant 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: * Patient is less than or equal to 18 years of age * Patient is newly diagnosed with high-risk neuroblastoma * Patient has adequate kidney and liver function * No prior therapy, unless an emergency situation requires local tumor treatment (discuss with PI) Exclusion Criteria: * Known severe hypersensitivity to ZD1839 or any of the excipients of this product * Any evidence, as judged by the investigator, of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease) * Evidence of any significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the trial. * Pregnant or breast feeding (women of child-bearing potential). * Concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St. John's Wort. * Treatment with a non-approved or investigational drug within 30 days before Day 1 of study treatment. * Any evidence of clinically active interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded). * Children with INSS 4 disease, age <12 months with all 3 favorable biologic features (non-amplified MYCN, favorable pathology and DNA index

Study Objectives Epithelial ovarian carcinoma (EOC) is the 5th leading cause of death among women. Long-term survival is poor for the majority of women with EOC because many present with advanced disease. Chemotherapy and cytoreductive surgery produces a 50% - 60% response rate but relapse is not uncommon. Adding more systemic agents has failed to show a clear benefit in survival and is associated with unacceptable toxicity. This phase II, dose-finding, open label trial will enrol women with newly diagnosed EOC and randomize them to receive one of 3 doses of a LMWH dalteparin in conjunction with standard adjuvant taxane- and platinum-based chemotherapy. The primary outcome is disease response, measured according to Gynaecologic Cancer Intergroup (GCIG) Cancer Antigen (CA)-125 response criteria. Secondary outcomes include symptomatic venous thromboembolism, bleeding, and compliance. The dose of dalteparin associated with the best response will be tested further in a phase III randomized clinical trial in the same patient population. Conditions: Ovarian Cancer Intervention / Treatment: DRUG: dalteparin Location: Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: Patients must meet all of the following criteria to be considered for enrolment: * Women with newly diagnosed, histologically proven EOC are potentially eligible. Patients with primary peritoneal or fallopian tube tumours of equivalent histology are also considered for enrolment. If open or true cut biopsy is not available, fine needle aspiration (FNA) showing an adenocarcinoma is considered diagnostic for EOC if all 4 (a to d) of the following conditions are satisfied: 1. Patient has a pelvic mass, AND 2. Any evidence of disease larger than 1 cm in the upper abdomen (unless proven stage IV), AND 3. Normal mammography within 6 weeks of randomization, AND 4. Serum CA-125/CEA greater than or equal to 25. If the ratio is less than 25, a barium enema (or colonoscopy) and gastroscopy (or radiological examination of the stomach) must be negative for a primary tumour. * Between the ages of 18 and 75. * FIGO stage IIB to IV disease. * A pre-study CA-125 level at least twice the upper limit of normal. * Eligible for standard adjuvant treatment with taxane- and platinum-based chemotherapy by meeting all of the following laboratory findings within 7 days prior to randomization: 1. Absolute granulocyte count of at least 1.5 x 10 9/L (1500 per cubic millimetre). 2. Platelet count of at least 150 x 109/L (100,000 per cubic millimetre). 3. Serum creatinine no greater than 177 micromol/L (2.0 mg/dL). 4. Total bilirubin level no greater than 1.5 times the upper limit of normal at the local centre. 5. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels no greater than 3 times the upper limit of normal of the local centre. Exclusion Criteria: * Borderline ovarian tumours. * Received prior chemotherapy or radiation therapy for EOC. * Received mouse antibodies anytime during the 28 days prior to the pre-study CA-125 level. * History of another malignancy, unless disease-free for 5 years or greater; non-melanomatous skin carcinoma or curatively treated carcinoma-in-situ of the cervix are excepted. * Eastern Cooperative Oncology Group (ECOG) performance score of 3 or 4. * Life expectancy less than 12 weeks. * Complete bowel obstruction at the time of study enrolment. * Receiving long-term anticoagulant therapy for an established indication (e.g., atrial fibrillation, mechanical heart valves). * Bleeding diathesis (e.g., evidence of DIC, hereditary or acquired bleeding disorder). * History of allergy to any heparin (e.g., heparin-induced thrombocytopenia). * Significant cardiac history including myocardial infarction within preceding 6 months, congestive heart failure, clinically relevant atrial or ventricular arrhythmias, history of 2nd or 3rd degree heart blocks unless pacemaker is implanted. * Serious medical conditions that preclude the administration of chemotherapy, anticoagulant therapy, or adherence to protocol, including but not exclusive to: 1. Allergic reactions to drugs containing cremophor or compounds chemically related to taxanes or platinum analogues. 2. Significant neurologic or psychiatric disorder that would impair obtaining informed consent and reliable follow-up. 3. Uncontrolled hypertension despite optimal medical therapy. 4. Active, uncontrolled infection. * Women who are pregnant or lactating or are of childbearing potential but are not using effective contraception. * Total body weight of less than 40 kg. * Concurrent treatment with experimental or investigational drugs. * Unable or unwilling to attend scheduled follow-ups. * Unable (e.g., language barrier, mental illness) to provide informed consent.

Study Objectives The goal of this clinical research study is to find the highest tolerable dose of the drugs clofarabine and cyclophosphamide that can be given together in the treatment of relapsed or refractory ALL. The safety of the combination treatment will also be studied. Objectives: Phase I: 1. To establish toxicities and safety of the proposed combination 2. To establish the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of the combination to proceed with the phase II part of the study Phase II: 3. To establish the efficacy (complete and overall response) of the proposed combination. 4. To analyze pharmacokinetic (PK) and pharmacodynamic (PD) properties of clofarabine as well as the impact on DNA repair of leukemic blasts with the proposed combination. Conditions: Burkitt's Lymphoma, Lymphoblastic Lymphoma, Acute Lymphoblastic Leukemia Intervention / Treatment: DRUG: Clofarabine, DRUG: Cyclophosphamide Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Previously treated ALL (including Burkitt's lymphoma and lymphoblastic lymphoma) in relapse or primary refractory. For patients in first relapse, the first remission duration may not exceed 12 months. * Age >= 21 years. * Zubrod performance status <= 3. * Adequate liver function (bilirubin <= 2.5 mg/dL and Serum glutamic pyruvic transaminase (SGPT or SGOT) <= 3 * ULN, unless considered due to tumor), and renal function (glomerular filtration rate [GFR] >= 60 mL/min). Even if organ function abnormalities are considered due to tumor, the upper limit for bilirubin is <= 5 mg/dL and creatinine <= 3 mg/dL. * Male and female patients who are fertile agree to use an effective barrier method of birth control (e.g., latex condom, diaphragm, cervical cap, etc.) to avoid pregnancy. Female patients need a negative serum or urine pregnancy test within 14 days of study enrollment (applies only if patient is of childbearing potential. Non-childbearing is defined as >= 1 year postmenopausal or surgically sterilized). Exclusion Criteria: * Patients with active heart disease (New York Heart Association (NYHA) class >= 3 as assessed by history and physical examination). * Patients with a cardiac ejection fraction (as measured by either Multi Gated Acquisition Scan (MUGA) or echocardiogram) < 45% are excluded. * Patients who receive other chemotherapy. Patients must have been off previous therapy for >= 2 weeks and must have recovered from acute toxicity of all previous therapy prior to enrollment. (Concurrent therapy for central nervous system (CNS) prophylaxis or treatment for CNS relapse is permitted). Treatment may start earlier if necessitated by the patient's medical condition following discussion with the Principal Investigator. * Pregnant and breast-feeding patients are excluded

Study Objectives This open-label, multicenter, randomized, controlled, Phase II study is planned to answer questions about how the drug, matuzumab (EMD 72000), works and is part of an effort aimed to develop better treatment for advanced lung cancer by combining matuzumab, a monoclonal antibody, with a chemotherapy treatment, called pemetrexed. Conditions: Lung Cancer, Non Small Cell Lung Carcinoma Intervention / Treatment: DRUG: Pemetrexed, DRUG: Matuzumab Location: United States, Germany, Austria Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Written informed consent provided prior to any screening procedure * Male or female, greater than (>) 18 years of age * Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) * Demonstrated PD on or after first-line chemotherapy for Stage IIIB/IV disease. The first-line therapy must consist of platinum-based regimens in combination with taxanes, gemcitabine or vinorelbine. Stage IIIB/IV participants must have measurable disease (tumor) without clinically significant pleural effusion unless the pleural effusion can be effectively drained prior to admission into the study * A chemotherapy-free interval of at least 3 weeks between the end of first-line chemotherapy and start of study treatment * At least 1 measurable lesion according to the modified World Health Organization (WHO) criteria * Archived tissue or cytologic sample available for the determination of epidermal growth factor receptor (EGFR) expression * Eastern cooperative oncology group (ECOG) performance status 0-1 * Life expectancy >12 weeks * Adequate baseline organ functions, defined as: Serum creatinine less than or equal to (<=)1.5*upper limit of normal (ULN). In case of borderline values for serum creatinine, creatinine clearance must be greater than or equal to (>=) 45 millimeters per minute (mL/min); Total bilirubin <1.5*ULN; Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) <=2.5*ULN (participants with liver metastases should have ALT/AST <5*ULN.); Absolute neutrophil count >=1500per cubic millimeter(mm^3); Platelet count >=100000/mm^3; Hemoglobin level >=10 grams per deciliter * If procreative potential (male or female), willingness to use effective contraceptive methods for the duration of treatment and continuing for 2 months after the last dose. Participants of procreative potential are defined as any fertile male, or any female who has experienced menarche and who is not postmenopausal (defined as age-related amenorrhea >=12 months) or who has not undergone successful surgical sterilization (hysterectomy or bilateral oophorectomy) Exclusion Criteria: * Radiotherapy or major surgery within 30 days prior to the start of study treatment * Prior treatment with an EGFR-directed therapy or with EGFR signal transduction inhibitors * Prior treatment with pemetrexed * Pregnant (confirmed by beta-human chorionic gonadotropin [β-HCG]) or lactating female * Weight loss >10% within 12 weeks prior to the start of study treatment * Documented or symptomatic brain metastases or leptomeningeal disease * Myocardial infarction within 6 months prior to the start of study treatment, uncontrolled congestive heart failure, or any current New York Heart Association Grade III or IV cardiovascular disorder despite treatment * Presence of a Grade >=2 preexisting skin disorder (except for alopecia) * Previous diagnosis of autoimmune disease with significant organ involvement * Concurrent malignancies or invasive carcinomas diagnosed within the past 5 years, except for adequately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix * Any significant disease that, in the Investigator's opinion, should exclude the participant from the study * History of significant neurologic or psychiatric disorder (for example, dementia, seizures, or bipolar disorder) * History of drug abuse within 6 months prior to the start of study treatment * Known conditions that require concurrent treatment with a nonpermitted drug * Presence of a contraindication to the study treatment(s) according to the current Investigator's Brochure (IB) for matuzumab and the labeling for pemetrexed * Known hypersensitivity to the study treatment or any of its components * Participation in another clinical study within 30 days prior to the start of study treatment

Study Objectives A multicenter, randomized, open-label, phase III trial of S-1 plus cisplatin (3 weekly) versus S-1 plus oxaliplatin chemotherapy for the first-line treatment of advanced gastric cancer Conditions: Gastric Cancer Intervention / Treatment: DRUG: S-1, DRUG: Cisplatin, DRUG: Oxaliplatin Location: Korea, Republic of Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Written informed consent before the enrollment * Age >=18 years old * Histologically/cytologically confirmed recurrent or metastatic gastric or esophagogastric junctional adenocarcinoma * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Patients able to swallow food and drugs * At least one measurable or evaluable lesion according to RECIST criteria version 1.1 * Adequate bone, hepatic, and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to first administration of study drugs * Absolute neutrophil count (ANC) >= 1,500/ uL, platelet >= 100,000/ uL, haemoglobin (Hb) >= 9.0 g/dl, * Serum creatinine <= 1.5 mg/dL (If serum creatinine is greater than 1.5 mg/dL, creatinine clearance [Ccr] should be 60 mL/min or greater. Ccr is calculated by Cockcroft-Gault formula or 24hr urine collection) * Total bilirubin <= 1.5 x upper limit of normal (ULN), AST/ALT levels <= 3.0 x ULN (AST/ALT levels <= 5.0 x ULN for patients with liver involvement of their cancer) * In patients who received adjuvant or neoadjuvant chemotherapy, completion of systemic chemotherapy 6 months before the study enrollment, and no previous administration of platinum derivatives * Estimated life expectancy of more than 3 months Exclusion Criteria: * Other histologic types than adenocarcinoma * Recurrence within 24 weeks following completion of adjuvant chemotherapy * R1 gastrectomy (i.e., microscopic residual disease) * History of another malignancy within the last five years from the day of written informed consent except cured basal cell carcinoma of skin and cured carcinoma in situ of uterine cervix * Radiotherapy within 4 weeks after randomization * History of significant neurologic or psychiatric disorders, and presence or history of CNS metastasis * Major surgery within 4 weeks before study entry, or insufficient recovery from major surgery (except the patients who received only open and closure or biopsy) * Other serious illness or medical conditions as follows; * Any following conditions occurred within 6 months before study entry: myocardial infarction, severe/unstable angina, bypass surgery for coronary artery/peripheral artery, congestive heart failure (NYHA class III or IV), cerebral infarction or transient ischemic attack * Conduction abnormality such as 2nd degree or greater AV block or severe arrhythmia that requires medical treatments (right bundle branch block (RBBB) is eligible, but left bundle branch block (LBBB) is not.) * Uncontrolled hypertension * Liver cirrhosis (Child Pugh Class B or greater) * Interstitial pneumonia, pulmonary fibrosis * Active viral hepatitis B * Uncontrolled diabetes mellitus * Uncontrolled ascites or pleural effusion * Uncontrolled active infection or sepsis * Administration of medications which may have potentially pharmacokinetic interaction with S-1, cisplatin, and oxaliplatin * Flucytosine, a fluorinated pyrimidine antifungal agent * Anti-viral agents, such as sorivudine, and brivudine, or chemical similar drugs * Warfarin (except, low dose warfarin for the purpose of prophylaxis), phenprocoumon * Phenytoin * Allopurinol * Participation to other clinical trials or administration of other investigational drugs within 30 days before the randomisation * Pregnant or lactating women * Women or men of child bearing potential not employing adequate contraception during study treatments or until the 3 months after the end of study treatments * Ineligible for the study at the discretion of investigators

Study Objectives Non-myeloablative approach for allogeneic transplant is a reasonable option, especially given that the median age at diagnosis is 55-60 years and frequently present compromised skin in these patients, which increases the risk of infection. Therefore, we propose a clinical study with allogeneic hematopoietic stem cell transplantation (HSCT) using a unique non-myeloablative preparative regimen, TLI/ATG, to treat advanced mycosis fungoides/Sezary syndrome (MF/SS). Conditions: Mycoses, Sezary Syndrome, Lymphoma, T-Cell, Cutaneous, Bone Marrow Transplant Failure, Lymphoma, Non-Hodgkin, Cutaneous T-cell Lymphoma Intervention / Treatment: DRUG: anti-thymocyte globulin, DRUG: cyclosporine, RADIATION: Lymphoid radiation 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: * Stage IIB-IV mycosis fungoides or Sezary syndrome, who have failed at least 1 standard systemic therapy or are not candidates for standard therapy. * Pathology reviewed and the diagnosis confirmed at Stanford University Medical Center. * Age > 18 years and <= 75 years. * Karnofsky Performance Status >= 70%. * Corrected DLCO >= 40% * Left ventricle ejection fraction (LVEF) > 30%. * ALT and AST must be <= 3X normal. Total bilirubin <= 3 mg/dL unless hemolysis or Gilbert's disease. * Estimated creatinine clearance >= 50 ml/min. * Have a related or unrelated HLA-identical donor or one antigen/allele mismatched in HLA-A, B, C or DRB1. * Signed informed consent. * Patients with prior malignancies diagnosed > 5 years ago without evidence of disease are eligible. * Patients with a prior malignancy treated < 5 years ago but have a life expectancy of > 5 years for that malignancy are eligible. Donor Inclusion Criteria * Age >=17. * HIV seronegative. * No contraindication to the administration of G-CSF. * Willing to have a central venous catheter placed for apheresis if peripheral veins are inadequate Exclusion Criteria: * Uncontrolled active infection. * Uncontrolled congestive heart failure or angina. * Pregnancy or nursing patients will be excluded from the study. * Those who are HIV-positive will be excluded from the study due to high risk of lethal infection after hematopoietic cell transplantation. Donor Exclusion Criteria * Serious medical or psychological illness. * Pregnant or lactating women are not eligible * Prior malignancies within the last 5 years except for non-melanoma skin cancers

Study Objectives - Hypothesis We hypothesise that intermittent dosing of the anti-angiogenic RTKI sunitinib or bevacizumab prior to systemic cisplatin and gemcitabine chemotherapy to transiently "normalise" tumour vasculature in patients with locally advanced or metastatic NPC will allow greater efficiency in drug and oxygen delivery, thus potentiating sensitivity to chemotherapy. We hypothesise that a loading dose of sunitinib for 7 days is required to achieve this sensitization effect prior to the first cycle of chemotherapy, and that this effect can subsequently be maintained by a 7 day course of sunitinib prior to each subsequent cycle of chemotherapy. The other hypothesis tested is that bevacizumab 7 days prior to chemotherapy will achieve normalization of tumor vasculature as well, and may induce changes in the tumor microenvironment that is beneficial for antitumour effect. Conditions: Nasopharyngeal Carcinoma Intervention / Treatment: DRUG: 12.5mg sunitinib with Cisplatin and Gemcitabine, DRUG: 25mg Sunitinib alternating with Cisplatin and Gemcitabine, DRUG: 7.5mg/kg Bevacizumab alternating with Cisplatin and Gemcitabine, DRUG: 2.5mg/kg Bevacizumab alternating with Cisplatin and Gemcitabine Location: Singapore Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: Patients may be included in the study only if they meet all of the following criteria: * Male or female patients aged 21 years and above. * Patients with histologically confirmed WHO Type II or III NPC. * Tumour stage III, IVA (T4 N0-2 M0), IVB (Any T N3 M0) or IVC (Any T Any N M1) according to the American Joint Committee on Cancer (AJCC) 2010 criteria. Alternatively, patients with locally advanced recurrent or metastatic NPC for which systemic chemotherapy is indicated will be eligible. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1. * Adequate organ function including the following: a. Bone marrow function i. Haemoglobin >= 9g/dl ii. Absolute neutrophil count (ANC) >= 1.5 x 109/L iii. Platelet count >= 100 x 109/L. b. Liver function i. Bilirubin < or = upper limit of normal (ULN) ii. Alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) < or = 2.5x ULN iii. Alanine transaminase (ALT) and aspartate transaminase (AST) < or = ULN iv. Prothrombin time (PT) within the normal range for the institution. c. Renal function i. Plasma creatinine within the normal range for the institution or calculated creatinine clearance (by the Cockcroft-Gault formula) > 60mL/min. d. Serum amylase and lipase < or = 1.5x ULN. * Life expectancy of at least 3 months. * Recovery from any previous drug- or procedure-related toxicity to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 Grade 0 or 1 (except alopecia), or to baseline preceding the prior treatment. * Signed informed consent obtained before any study specific procedure. Subjects must be able to understand and be willing to sign the written informed consent. Exclusion Criteria: Patients will be excluded from the study for any of the following reasons: * Previous or concurrent anti-cancer chemotherapy, immunotherapy, radiotherapy or any other investigational therapy. * Patients who cannot swallow or patients with chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the tested product. * Any concomitant condition that could compromise the objectives of this study and/or the patient's compliance (eg. severe medical conditions such as uncontrolled infection, poorly controlled diabetes mellitus, hypercalcaemia, psychiatric disorders). * Major thoracic and/or abdominal surgery in the preceding 3 weeks. * Known human immunodeficiency virus (HIV) seropositivity, hepatitis B or C seropositivity. * In the investigator's opinion, patients with a current or previous history of clinically significant liver disease within the previous 2 years. * History of cardiac disease: congestive heart failure > New York Heart Association (NYHA) Class II; active coronary artery disease (unstable angina [anginal symptoms at rest] or new-onset angina [began within the last 3 months] or myocardial infarction within the past 6 months). Cardiac arrhythmias requiring anti-arrhythmic therapy (β-blockers or digoxin are permitted). * Uncontrolled hypertension (failure of diastolic blood pressure to fall below 90 mmHg, despite the use of >= 3 anti-hypertensive drugs or systolic blood pressure greater than 150 mmHg). * Dehydration NCI-CTCAE Grade 2 or higher. * Subjects with serious non-healing wound, ulcer, or bone fracture. * Subjects with arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the 6 months before start of study medication. * Subjects with renal impairment (creatinine clearance by the Cockcroft-Gault formula) <= 60mL/min) or on dialysis. * Persistent proteinuria of NCI-CTCAE Grade 3 or higher (> 3.5 g/24 hours, measured by urine protein/creatinine ratio on a random urine sample). * Clinically significant bleeding (NCI-CTCAE Grade 3 or higher) within 30 days prior to start of study medication. * Subjects unable to swallow oral medications. * Subjects with seizure disorder requiring anticonvulsant medication. * History of organ allograft. * Subjects with evidence or history of disorders of coagulation or thrombosis. * Pregnancy or breastfeeding. * Women of childbearing potential not employing adequate contraception. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of study medication, and a negative result must be documented before start of study medication. Women of childbearing potential and men, must agree to use adequate contraception (barrier method of birth control) upon signing the informed consent form until at least 3 months after the last study drug administration. The definition of adequate contraception will be based on the judgment of the treating investigator or a designated associate. * Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results. * Known or suspected allergy to the investigational agent or any agent given in association with this study. * Any condition that is unstable or could jeopardize the safety or compliance of the subject in the study. * Previous or concurrent cancer which is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1) or any cancer curatively treated > 3 years prior to study entry. * Interstitial lung disease with ongoing signs and symptoms at the time of screening.

Study Objectives This is an open, monocentric, pilot study to determine the metabolic activity (glucose-uptake) in vivo during monotherapy with pazopanib in comparison to combination therapy with pazopanib plus paclitaxel and to investigate the transcriptional profile of cutaneous melanoma metastasis before and during the therapy (pazopanib vs. pazopanib plus paclitaxel) in subjects with unresectable Stage III or Stage IV melanoma who have not received prior cytotoxic chemotherapy. Primary Objective: Evaluation of metabolic activity in vivo Secondary Objective: Determination of changes in gene expression profiling Evaluation of the antitumor activity of the combination in terms of progression free survival (PFS). Changes in S100 and LDH during therapy at the same time points as FDG-PET/CT (a combined serum measurement of S100 and LDH) * Trial with medicinal product Conditions: Melanoma Intervention / Treatment: DRUG: Pazopanib/Paclitaxel Location: Switzerland Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion criteria: * Age >= 18 years * Diagnosis of histologically or cytologically confirmed melanoma stage III or IV. * Fresh tumor tissue must be provided for all subjects for biomarker analysis before (within 14 days prior to treatment start) and during (on day 10 of the pazopanib monotherapy and the last day of the treatment with pazopanib, day 70) treatment with investigational product (asservation in RNAlater, for kryo asservation, and for cell cultures) * Assessable metastases (skin or superficial lymph nodes with a minimal diameter 1 cm) * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate organ system function Exclusion criteria: * Prior malignancy. * Central nervous system (CNS) metastases * Corrected QT interval (QTc) > 480 msecs using Bazett's formula. * 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 * History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. * Presence of uncontrolled infection * Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding * Evidence of active bleeding or bleeding diathesis * Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia. * Prior exposure to the study drug pazopanib

Study Objectives The addition of abiraterone acetate to standard treatment of radiotherapy and short-term androgen deprivation will increase the frequency of undetectable PSA. Conditions: Prostate Cancer Intervention / Treatment: DRUG: Abiraterone acetate, DRUG: Androgen deprivation, RADIATION: Radiation Therapy, DRUG: Prednisone 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: * One of the following high risk criteria: * Gleason Score 7 with PSA <= 20 ng/ml and clinical T1-2, or * Gleason Score 8-10, PSA <= 20 ng/ml and clinical T1-2a, or * PSA 10.1-40 ng/ml with GS < 7 and clinical T1-2, or * Clinical T3 with Gleason Score < 7 and PSA <= 10 ng/ml. * ECOG Performance Status <= 1 * Digital rectal exam within 90 days of registration on study * CBC with differential with adequate bone marrow function defined as follows: * Absolute neutrophil count (ANC) >= 1,500 cells/mm3, Platelets > 100,000/µL and Hemoglobin >= 9g/dL * Serum potassium >= 3.5 mEq/L * Serum albumin > 3.0 g/dl * Total bilirubin < 1.5 X of institutional upper limit of normal (ULN) * AST(SGOT)/ALT(SGPT) < 1.5 X ULN * Calculated creatinine clearance > 60 mL/min * Age > 18 years * Able to swallow a whole tablet and take abiraterone acetate on an empty stomach (defined as no food for two hours before and one hour after abiraterone acetate ingestion) * Ability to understand and sign a written informed consent document * Written authorization for use and release of health and research study information has been obtained * Be willing/able to adhere to the prohibitions and restrictions specified in this protocol * Subjects who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protections as determined acceptable by the principal investigator during the study and for 1 week after the last dose of abiraterone acetate. Exclusion Criteria: * Bone, visceral or soft tissue metastasis, including lymph nodes (>2 cm in longest diameter) * Prior therapy for prostate cancer [Exceptions: LHRH agonist or antagonist may have been initiated within 30 days prior to enrollment. Bicalutamide may have been given within 60 days of enrollment as long as it has been stopped at least 7 days before enrollment and total duration was no longer than 30 days. This is to allow enrollment of those who have been given bicalutamide as a bridge for LHRH agonist/antagonist. It is highly unlikely a short non-overlapping course of bicalutamide will interact with abiraterone acetate in a measurable way. Previous alpha-reductase inhibitor use allowed IF patient has not been taking for at least 30 days prior to abiraterone acetate initiation, OR if alpha reductase inhibitor was not used as a primary treatment of prostate cancer and the PSA on alpha-reductase inhibitor remains within eligibility when doubled. ] * Known serum testosterone <= 150 ng/dl or symptoms of hypogonadism (fatigue, hot flashes, hair loss, loss of muscle mass, osteoporosis, low libido, depression) prior to ADT initiation not explained by other medical co-morbidity OR history of testosterone supplement. If questionable, serum testosterone level greater than 150 ng/dl can be used to exclude hypogonadism. * Previous malignancy within 3 years other than non-melanomatous skin cancer and non-muscle invasive bladder cancer * Previous pelvic radiotherapy that would prevent prostate/SV irradiation * Uncontrolled hypertension (systolic BP >= 160 mmHg or diastolic BP >= 95 mmHg). Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy * History of gastrointestinal disorders that may interfere with the absorption of study drug (including gastric bypass surgery) * Concurrent spironolactone use * Significant concurrent medical condition that would make prednisone/prednisolone use contraindicated or would interfere with the patient's ability to participate in the trial * Receiving any investigational agents currently or within 30 days prior to study screening * Prior demonstrated hypersensitivity, intolerance or allergy to abiraterone acetate, prednisone or their excipients * Active co-morbidity, defined as follows: * Chronic liver disease with cirrhosis (Child-Pugh B or C) or active hepatitis B or C * History of pituitary or adrenal dysfunction * Poorly controlled diabetes mellitus (A1c >9% or history of complications including peripheral neuropathy, end organ damage, hospitalization, amputation) * Poorly controlled glaucoma * Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class III-IV heart disease or known cardiac ejection fraction measurement of < 50% at baseline. * Clinical evidence of active infection of any type, including active or symptomatic viral hepatitis. * Known immune deficiency and/or HIV-positive patients * Any medical condition that warrants long-term corticosteroid use in excess of study dose * Patients taking strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) * Any condition that in the opinion of the Principal Investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing the study requirements

Study Objectives The purpose of this randomized, double-blind and placebo-controlled pilot study is to investigate whether dexmedetomidine when used as an adjuvant to general anesthesia can decrease the harmful effects of anesthesia and surgery on intelligence development in pediatric patients undergoing craniotomy. Conditions: Brain Neoplasms Intervention / Treatment: DRUG: dexmedetomidine, DRUG: normal saline Location: China Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE4 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Age of >= 2 years, but no more than 12 years; * Plan to undergo selective craniotomy under general anesthesia for intracranial tumor resection; * Written informed consent signed by legal guardians. Exclusion Criteria: * Refused to participate by the legal guardians; * Body weight lower than the 3rd percentile or higher than 97th percentile of the normal body weight reference; * American Society of Anesthesiologists physical classification of IV or higher; * Unable to complete preoperative intelligence assessment because of coma, dysnoesia, or language barrier; * Diagnosed pulmonary disease (including acute respiratory tract infection) or cardiovascular disease (including congenital heart disease, hypertension, hypotension, bradycardia, atrioventricular block, or cardiac insufficiency); * Abnormal liver or renal function (liver enzyme or creatinine higher than 1.5 times of the upper normal limit; * Other congenital diseases that may affect the development of the nervous system (such as Down's Syndrome); * Allergy to dexmedetomidine; * Other conditions that are considered unsuitable for study participation by the attending pediatricians or investigators.

Study Objectives Enzastaurin given daily to patients with non-small cell lung cancer who have failed at least one prior therapy. Conditions: Non-Small-Cell Lung Carcinoma Intervention / Treatment: DRUG: Enzastaurin HCL 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: * Must be at least 18 years old * Must have been diagnosed with advanced or metastatic non-small cell lung cancer * Must be able to visit the doctor's office every 28 days for 6 months or longer. Exclusion Criteria: * Pregnant or breastfeeding women * Have other significant medical problems as determined by your physician * Are unable to swallow tablets * Have a history of significant heart disease

Study Objectives This is a randomised, double-blind, parallel groups, vehicle controlled, 8-week phase 2 trial. The objective is to evaluate efficacy of ingenol mebutate gel 0.06 % after once daily treatment for 2, 3 or 4 consecutive days compared to vehicle gel Conditions: Actinic Keratosis Intervention / Treatment: DRUG: ingenol mebutate, OTHER: Placebo Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: Subjects with 5 to 20 clinically typical, visible and discrete AKs within a contiguous area of approximately 250 cm² sun-damaged skin on either trunk (except chest), or extremities Exclusion Criteria: * Location of the treatment area (trunk (except chest) or extremities) * within 5 cm of an incompletely healed wound, * within 5 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) * Prior treatment with ingenol mebutate within the selected treatment area * Lesions in the treatment area that have: * atypical clinical appearance (e.g., hypertrophic,hyperkeratotic or cutaneous horns) and/or, * recalcitrant disease (e.g., did not respond to cryotherapy on two previous occasions)

Study Objectives This is a phase 2, randomized, double-blind, multi-center clinical study to evaluate efficacy and safety of a maintenance therapy with the immunomodulator MGN1703 compared to placebo control. The study will be conducted in patients with advanced colorectal carcinoma (AJCC Stage IV) with disease control after first-line standard chemotherapy regimens. Conditions: Advanced Colorectal Carcinoma Intervention / Treatment: DRUG: MGN1703, DRUG: Placebo Location: Germany, Czech Republic, United Kingdom, Austria, Russian Federation, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Male and female subjects older than 18 years of age * Histologically confirmed colorectal carcinoma * Radiological confirmation of unresectable advanced colorectal carcinoma (AJCC Stage IV) prior to start of initial first-line therapy * At least one measurable lesion according to RECIST measured within 2 weeks prior to treatment start in case of partial response or stable disease * Prior initial first-line therapy included oral or intravenous fluoropyrimidines/leucovorin,irinotecan or oxaliplatin with or without a standard dose of bevacizumab lasted between 4.5 and 6 months and finished (last day of last cycle) within 2 weeks prior to treatment start (treatment duration with irinotecan or oxaliplatin should not be less than 3 months) * Patients who achieved disease control measured as objective response or disease stabilization after initial first-line therapy * No curative standard therapy is available for the patient after first-line treatment * ECOG performance status 0-1 * Adequate organ function, hemoglobin >= 9 g/L, white blood cell count (WBC) >= 3.0 x 109/L, absolute neutrophil count >= 1.5 x 109/L, platelets > 100 x109/L, aspartate and alanine aminotransferase (AST and ALT) <= 2.5 x ULN, bilirubin < 1.5 x ULN, blood creatinine <= 1.5 X ULN, prothrombin time (PT) and activated thromboplastin time (aPTT) within normal range * Negative pregnancy test in women with childbearing potential * Expected adequacy of follow-up * Signed informed consent form (ICF) Exclusion Criteria: * More than one line of systemic chemotherapy for metastatic colorectal carcinoma * Tumor progression after initial first-line therapy * Clinically significant concomitant diseases or conditions, which in opinion of the investigator would lead to an unacceptable risk for the subject to participate in the study * Prior or current other malignancy, except adequately treated superficial bladder cancer, basal or squamous cell carcinoma of the skin or other cancer for which the subject has been disease free for more than 3 years * Known central nervous system metastases * Active or uncontrolled infections * Transfusion-dependent anemia * History of autoimmune disease or immune deficiency * Known hypersensitivity to oligonucleotides or excipients of the formulation * Pregnancy and/or nursing * Concurrent chronic systemic immune therapy or immunosuppressant medication, including steroid treatment * Concurrent chemotherapy, hormonal therapy (except hormonal contraception and hormonal replacement therapy for menopausal women), or immunotherapy within the last 2 weeks prior to randomization or during the conduct of the study - Concurrent radiotherapy within the last 6 months prior to randomization or during the conduct of the study * Known HIV seropositivity or active hepatitis B or C infection * Planned major surgery during the study * Participation in another clinical study with other investigational drugs within 30 days prior to the first treatment day * Vaccination within 3 months prior to the first treatment day * Any medical, mental, psychological or psychiatric condition which in opinion of the investigator would not permit the subject to complete the study or understand the patient information * Presence of drug and/or alcohol abuse

Study Objectives The purpose of this study is to determine a dose of LY2784544 that may be safely administered to participants with myeloproliferative neoplasms. Conditions: Myeloproliferative Neoplasms of, Polycythemia Vera, Essential Thrombocythemia, Myelofibrosis Intervention / Treatment: DRUG: LY2784544 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: Have a diagnosis of polycythemia vera (PV), essential thrombocythemia (ET), or myelofibrosis (MF, primary or secondary) PV and ET participants must have failed or are intolerant of standard therapies or refuse to take standard medications MF participants must meet at least one of the following criteria: * Have intermediate-1, intermediate-2, or high-risk MF according to the Dynamic International Prognostic Scoring System (DIPSS) plus; or * Have symptomatic MF with spleen greater than 10 cm below left costal margin; or * Have post-polycythemic MF (post-PV MF); or * Have post-essential thrombocythemic MF (post-ET MF) All participants must meet the following criteria: * Have given written informed consent prior to any study-specific procedures * Have adequate organ function, including: * Hepatic: Direct bilirubin less than or equal to 1.5 times upper limits of normal (ULN), alanine transaminase (ALT), and aspartate transaminase (AST) less than or equal to 2.5 times ULN * Renal: Serum creatinine less than or equal to 1.5 times ULN * Bone Marrow Reserve: Absolute neutrophil count (ANC) >=1000/mcL, platelets >=25,000/mcL, platelets >=50,000 for PV or ET participants. * Have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) scale * Have discontinued all previous approved therapies for MF, including any chemotherapy, immunomodulating therapy (for example, thalidomide, interferon-alpha), immunosuppressive therapy (for example, corticosteroids >10 mg/day prednisone or equivalent), radiotherapy, and erythropoietin, thrombopoietin, or granulocyte colony-stimulating factor (GSF) for at least 14 days and recovered from the acute effects of therapy. Hydroxyurea used to control blood cell counts is permitted at study entry if the participant has been maintained on a stable dose for at least 4 weeks. Low dose acetylsalicylic acid (aspirin; 81 or 100 mg) is permitted as well * Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures * Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the study and for 3 months following the last dose of study drug * Females with child-bearing potential must have had a negative urine pregnancy test less than or equal to 7 days before the first dose of study drug and must also not be breastfeeding * Are able to swallow capsules/tablets * For participants who have undergone recent major surgery, at least 28 days must have elapsed between surgery and study participation, and the participant must have achieved, in the opinion of the treating physician, at least a good recovery from the surgical procedure Exclusion Criteria: Potential participants may not be included in the study if any of the following apply during screening: * Have received treatment within 14 days of the initial dose of study drug with an experimental agent that has not received regulatory approval for any indication * Have a QTc interval >470 milliseconds (msec) using Bazett's formula * Have serious preexisting medical conditions that, in the opinion of the investigator, would preclude participation in the study (for example, a gastrointestinal (GI) disorder causing clinically significant symptoms such as nausea, vomiting, and diarrhea, or malabsorption syndrome) * Are currently being treated with agents that are metabolized by cytochrome P450 (CYP)3A4 with a narrow therapeutic margin (for example, alfentanil, cyclosporine,diergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus) or CYP2B6 (for example, cyclophosphamide, ifosfamide, tamoxifen, efavirenz, propofol, methadone, and bupropion) * Have received a hematopoietic stem cell transplant * Have a second primary malignancy that in the judgment of the investigator and sponsor, may affect the interpretation of the results * Have an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required) * Have a history of congestive heart failure with New York Heart Association (NYHA) Class greater than 2 (NYHA Class 1 and 2 are eligible), unstable angina, recent myocardial infarction (within 6 months prior to administration of study drug), or documented history of ventricular arrhythmia

Study Objectives The purpose of this study is 2-fold: initially, in the dose escalation phase, the goal is to determine the safety profile of orally administered brigatinib, including: the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), recommended phase 2 dose (RP2D), and pharmacokinetic (PK) profile. Then, once the RP2D is established, an expansion phase will assess the preliminary anti-tumor activity of brigatinib, both in non-small cell lung cancer (NSCLC) with ALK gene rearrangement (including participants with active brain metastases) or mutated EGFR, and in other cancers with abnormal targets against which brigatinib is active. Conditions: Lymphoma, Large-Cell, Anaplastic, Carcinoma, Non-Small-Cell Lung Intervention / Treatment: DRUG: Brigatinib Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: General Eligibility Criteria * All participants must have tumor tissue available for analysis. If sufficient tissue is not available, participants must undergo a biopsy to obtain adequate samples. For participants in expansion cohorts 2, 3 and 5, for whom failure of prior therapy is specified (crizotinib for cohorts 2 and 5, one epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) for cohort 3), tumor tissue must be available following failure of the prior therapy. * Must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST). * Male or female participants >= 18 years old. * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. * Minimum life expectancy of 3 months or more. * Adequate renal and hepatic function. * Adequate bone marrow function. * Normal QT interval on screening electrocardiogram (ECG) evaluation. * For females of childbearing potential, a negative pregnancy test must be documented prior to enrollment. * Female participants who are of childbearing potential and fertile male participants must agree to use an effective form of contraception with their sexual partners throughout study participation. * Signed and dated informed consent indicating that the participant has been informed of all pertinent aspects of the study. * Willingness and ability to comply with scheduled visits and study procedures. Cohort-specific Eligibility Criteria PART 1: Dose Escalation Phase: * Histologically confirmed advanced malignancies. All histologies except leukemia; * Refractory to available therapies or for whom no standard or available curative treatments exist; * Tumor tissue available for analysis. PART 2: Expansion cohorts (5 additional cohorts): * Expansion cohort 1: Non-small cell lung cancer (NSCLC) participants whose tumors exhibit anaplastic lymphoma kinase (ALK) rearrangements and who have not been treated with previous ALK inhibitors. i. Histologically or cytologically confirmed NSCLC; ii. Tumor tissue available for analysis (see General Eligibility Criterion 1; iii. History of ALK rearrangement by fluorescence in situ hybridization (FISH); iv. No prior ALK inhibitor therapy; 2. Expansion cohort 2: NSCLC participants whose tumors exhibit ALK rearrangements and who are resistant to crizotinib: i. Histologically or cytologically confirmed NSCLC; ii. Tumor tissue available for analysis (see General Eligibility Criterion 1); iii. History of ALK rearrangement by FISH; iv. Resistant to crizotinib (and have not received any other prior ALK inhibitor therapy); 3. Expansion cohort 3: NSCLC participants whose tumors exhibit an epidermal growth factor receptor EGFR-T790M mutation and who are resistant to 1 prior EGFR TKI: i. Histologically or cytologically confirmed NSCLC ii. Previous treatment with only 1 EGFR TKI for which the last administration was within 30 days of the initiation of brigatinib; iii. Documented evidence of an EGFR-T790M mutation following disease progression on the most recent EGFR TKI therapy; iv. No intervening systemic therapy between cessation of the EGFR TKI and initiating brigatinib; v. Tumor tissue available for analysis (see General Eligibility Criterion 1). 4. Expansion cohort 4: Participants with any cancers with abnormalities in ALK or other brigatinib targets. Examples include, but are not limited to, anaplastic large cell lymphoma (ALCL), diffuse large-cell lymphoma (DLCL), inflammatory myofibroblastic tumors (IMT), and other cancers with ALK abnormalities, or tumors with ROS1 fusions: i. Histologically confirmed lymphomas and other cancers, with the exception of leukemias; ii. Tumor tissue available for analysis (see General Eligibility Criterion 1). 5. Expansion Cohort 5: NSCLC participants whose tumors exhibit ALK rearrangements and who have active, measurable brain metastases: i. Histologically or cytologically confirmed NSCLC: ii. Tumor tissue available for analysis (see General Eligibility Criterion 1); iii. History of ALK rearrangement by FISH; iv. Either crizotinib naive or resistant; v. Have at least one measurable brain lesion (>= 10 mm by contrast enhanced, T1 weighted magnetic resonance imaging [cMRI]). Previously treated brain lesions by stereotactic radiosurgery (SRS) or surgical resection should not be included as a target or non-target lesion; vi. Previously untreated brain metastases with radiologically documented new or progressing brain lesions. Unequivocal progression of previously treated lesions (non-SRS and non-surgically treated lesions) at least 3 months after the last treatment; vii. Neurologically stable. Participants must be on a stable or deceasing dose of corticosteroids and/or have no requirement for anticonvulsants for 5 days prior to the baseline MRI and for 5 days prior to initiating brigatinib. Exclusion Criteria: * Received an investigational agent <= 14 days prior to initiating brigatinib. * Received systemic anticancer therapy (including monoclonal antibodies and irreversible TKIs such as afatinib or dacomitinib) or radiation therapy <= 14 days prior to initiating brigatinib. a. Except for a reversible TKI (ie, erlotinib or gefitinib) or crizotinib, which are allowed up to 72 hours prior to initiating brigatinib, provided that the participant is free of treatment-related toxicity that might confound the safety evaluation of brigatinib. * Received any prior agents targeted against ALK, with the exception of crizotinib, or received more than 1 prior EGFR TKI. a. Re-challenge with the same TKI is allowed. * Major surgery within 28 days prior to initiating brigatinib. * Brain metastases that are neurologically unstable or require anticonvulsants or an increasing dose of corticosteroids. 1. Participants with previously treated brain metastases without evidence of disease or recurrence are allowed for cohorts 1-4. 2. Participants with evaluable but non-measurable, active brain lesions who otherwise meet the criteria for cohort 5 for CNS disease can be enrolled in other cohorts. * Significant uncontrolled or active cardiovascular disease. * Uncontrolled hypertension (diastolic blood pressure [BP] > 100 mm Hg; systolic > 150 mm Hg). * Prolonged QT interval, or being treated with medications known to cause Torsades de Pointes. * History or presence of pulmonary interstitial disease or drug-related pneumonitis. * Ongoing or active infection. The requirement for intravenous (IV) antibiotics is considered active infection. * Known history of human immunodeficiency virus (HIV). Testing is not required in the absence of history. * Pregnant or breastfeeding. * Malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of brigatinib. * Any condition or illness that, in the opinion of the Investigator, would compromise participant safety or interfere with the evaluation of the safety of the drug. * Leptomeningeal carcinomatosis and spinal cord compression. In the case of suspected meningeal involvement, a negative lumbar puncture prior to study entry is required.

Study Objectives This study will investigate the safety and tolerability of SLN124 in patients with Thalassaemia or patients with Very Low- and Low-risk Myelodysplastic Syndrome (MDS) after single ascending s.c. doses and multiple doses in healthy male and female subjects. Up to 7 cohorts of 56 patients with Thalassaemia and up to 7 cohorts of 56 patients with MDS will be enrolled. Each subject will receive single or multiple doses of SLN124 or placebo given by subcutaneous (s.c) injection. Conditions: Non-transfusion-dependent Thalassemia, Low Risk Myelodysplastic Syndrome, Very-Low Risk Myelodysplastic Syndrome Intervention / Treatment: DRUG: SLN124, DRUG: Placebo Location: Israel, Jordan, Germany, Thailand, Italy, United Kingdom, Malaysia Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * Adult with alpha- or beta-thalassaemia or compound heterozygous haemoglobin E/beta-thalassaemia or adult with very low- or low-risk MDS according to the 2016 revision to the World Health Organisation classification. * All subjects must agree to adhere to appropriate contraception requirements. * Subjects must provide written informed consent and be able to comply with all study requirements. * Body mass index >=18 kg/m2 and <=35 kg/m2 at screening. * At least one of: a) Mean ferritin >250 μg/L based on a minimum of 2 measurements >=1 week apart within 20 days before the planned dosing day, in the absence of active significant infection; b) Mean TSAT >40% measured on a minimum of 2 occasions >=1 week apart within 20 days before the planned dosing day; c) Liver iron >3 mg Fe/g dry weight, measured according to local procedures. * Mean baseline haemoglobin concentration >=5 g/dL and <=11 g/dL, based on a minimum of 2 measurements >=1 week apart, within 20 days before the planned dosing day. Exclusion criteria * Adult with haemoglobin S/alpha-thalassaemia or haemoglobin S/beta-thalassaemia or adult with secondary MDS, i.e., MDS that is known to have arisen because of chemical injury or treatment with chemotherapy and/or radiation for another disease. * History of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc, or intolerance to s.c. injections. * Known infection with HIV, or active infectious hepatitis A, B, or C virus. * Any conditions which, in the opinion of the Investigator, would make the subject unsuitable for enrolment in the study or could interfere with the subject's participation in, or completion of the study. * History or clinical evidence of alcohol or illegal drug misuse within 2 years before screening. * Currently using ESA, or plan to use ESA at any point during the study. * Require daily treatment with 1 or more non-steroidal anti-inflammatory drugs during the study period. Paracetamol will be permitted for use as an antipyretic and/or analgesic. * Treatment, or change in treatment with prohibited medications as specified in the protocol * Treatment with ICT where the subject has not been on a stable dose for at least 8 weeks before screening or it is planned to initiate ICT therapy during the study. * Clinically significant cardiac disease * Clinically significant pulmonary disease For subjects with thalassaemia: * Treatment, or change in treatment with prohibited medications as specified in the protocol * currently and anticipated to receiving more than 5 units of RBCs during the 24 weeks to 6 weeks period before first dose of study drug. For subjects with very low / low-risk MDS: * Previous allogeneic or autologous stem cell transplantation. * Currently or planned to receive treatment with a corticosteroid for MDS within 8 weeks before screening. * Currently or planned to receive treatment with haematopoietic growth factors (e.g., eltrombopag, romiplostim) within 8 weeks before screening.

Study Objectives This phase II open label study will evaluate adolescents (≥ 16 years of age) and adults with neurofibromatosis type-1 (NF1) and plexiform neurofibromas treated with the MEK inhibitor PD-0325901. The primary aim of the study will be to assess quantitative radiographic response in a target lesion. Subjects will receive PD-0325901 by mouth on a bid dosing schedule of 2 mg/m2/dose with a maximum dose of 4 mg bid. Each course is 4 weeks duration, and subjects will receive drug on a 3 week on/1 week off schedule. Subjects may receive additional courses beyond course 8 only if there is at least 15% reduction in volume of the target tumor. Subjects who have a 20% or greater reduction in target tumor volume at the end of 12 courses can continue on therapy for up to an additional year (maximum of 24 total courses). However, subjects who do not achieve at least 15% reduction in volume of the target tumor after 8 courses (\~8 months) will be considered treatment failures and taken off study. The Primary purpose of this protocol is to determine whether PD-0325901 results in objective radiographic responses based on volumetric MRI measurements in adolescents and adults with NF1 and growing or symptomatic inoperable PN. There are several secondary aims of this protocol: To evaluate the feasibility and toxicity of chronic PD-0325901 administration in this patient population To estimate the objective response rate of up to 2 non-target plexiform neurofibromas to PD-0325901 by MRI To characterize the pharmacokinetic profile of PD-0325901 when administered to this patient population To evaluate quality of life and pain during treatment with PD-0325901 Conditions: Neurofibromatosis Type 1 and Growing or Symptomatic, Inoperable PN Intervention / Treatment: DRUG: PD-0325901 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: * All studies to determine eligibility must be performed within 2 weeks prior to enrollment unless otherwise indicated below. All clinical and laboratory data required for eligibility of a subject must be available in the subject's medical or research record. * All subjects must have EITHER the clinical diagnosis of NF1 using the NIH Consensus Conference criteria OR have a constitutional NF1 mutation documented in a CLIA/CAP certified lab. * Subjects must have plexiform neurofibroma(s) that are progressive OR are causing significant morbidity, such as (but not limited to) head and neck lesions that are compromising the airway or great vessels, brachial or lumbar plexus lesions that are causing nerve compression and loss of function, lesions causing major deformity (e.g., orbital lesions) or are significantly disfiguring lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions. Subjects with paraspinal plexiform neurofibromas will be eligible for this trial. Histologic confirmation of tumor is not necessary in the presence of consistent clinical and radiographic findings * For subjects enrolled for tumor progression, progression is defined as: * Presence of new plexiform neurofibroma on MRI or CT (documented by comparison with prior MRI or CT), OR * A measurable increase in plexiform neurofibroma size (>= 20% increase in the volume, or a >= 13% increase in the product of the two longest perpendicular diameters, or a >= 6% increase in the longest diameter) documented by comparison of two scans (MRI or CT) approximately one year or less prior to evaluation for this study. * For subjects enrolled for a "major deformity" or "significantly disfiguring" tumor, eligible tumors will be limited to tumors of the head & neck or those on other areas of the body that are unable to be concealed by standard garments. In order to enroll a plexiform neurofibroma for these indications, the Study Chair or Co-Chair must be contacted to review subject eligibility prior to enrollment. * Measurable disease: Subjects must have measurable plexiform neurofibroma(s) amenable to volumetric MRI analysis. The target lesion must be seen on at least 3 consecutive MRI slices and the field of view must contain the entire tumor of interest. Tumors must be at least 3 mL in volume (most PNs 3 cm in longest diameter will meet this criteria). If the tumor is <3 cm in longest diameter, the subject may still be eligible. Central review of the MRI of the target plexiform is required prior to enrollment to ensure that the tumor is measurable and amenable to volumetric analysis. After consenting, images will be sent for Central review * Age: Subjects must be >= 16 years of age at the time of study entry. * Durable Power of Attorney: Adults who are unable to provide informed consent will NOT be enrolled on this study. * Performance Level: Karnofsky greater than or equal to 50% Note: Subjects who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. * Prior Therapy: Subjects are only eligible if complete resection of a plexiform neurofibroma with acceptable morbidity is not feasible, or if a subject with surgical option refuses surgery. * Subjects who underwent surgery for a progressive plexiform neurofibroma will be eligible to enter the study after the surgery, provided the plexiform neurofibroma was incompletely resected and is evaluable by volumetric analysis. * Subjects may have been previously treated for a plexiform neurofibroma or other tumor/malignancy, but must have fully recovered from the acute toxic effects of all prior chemotherapy or radiotherapy prior to entering this study. * Myelosuppressive chemotherapy: Must not have received within 4 weeks of entry onto this study. * Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor that supports platelet, red or white cell number or function. * Biologic (anti-neoplastic agent): At least 14 days since the completion of therapy with a biologic agent. These subjects must be discussed with the Study Chair on a case-by-case basis. * Investigational Drugs: Subjects must not have received an investigational drug within 4 weeks. * Steroids: Subjects with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids if necessary. * 6 months from involved field radiation to index plexiform neurofibroma(s); 6 weeks must have elapsed if subject has received radiation to areas outside index plexiform neurofibroma(s). Subjects who have received radiation to the orbit at any time are excluded. * Surgery: At least 2 weeks since undergoing any major surgery and must be recovered from effects of surgery. * Organ Function Requirements * Adequate Bone Marrow Function * Adequate Renal Function * Adequate Liver Function Exclusion Criteria: * Chronic treatment with systemic steroids or another immunosuppressive agent. Subjects with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids if necessary. * Evidence of an active optic glioma or other low-grade glioma, requiring treatment with chemotherapy or radiation therapy. Subjects not requiring treatment are eligible for this protocol. * Patients with malignant glioma, malignant peripheral nerve sheath tumor, or other malignancy requiring treatment in the last 12 months. * Subjects who have received radiation to the orbit at any time previously * Subjects with glaucoma, intraocular pressure >21 mmHg, or any other significant abnormality on ophthalmic examination (performed by an ophthalmologist). * Ophthalmological findings secondary to long-standing Optic Pathway Glioma such as optic nerve pallor or strabismus will NOT be considered significant for the purposes of the study. * Tumor not able to be reliably evaluated by volumetric analysis. * Other concurrent severe and/or uncontrolled medical disease, which could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper GI tract ulceration, congestive heart failure, etc.) * Subjects who have an uncontrolled infection. * Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of PD-0325901 (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection). A nasogastric tube (NG tube) or gastric tube (G tube) is allowed. * Women who are pregnant or breast feeding. * Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during the period they are receiving the study drug and for 3 months thereafter. Abstinence is an acceptable method of birth control. Women of childbearing potential will be given a pregnancy test within 7 days prior to administration of PD-0325901 and must have a negative urine or serum pregnancy test. * History of noncompliance to medical regimens. * Subjects unwilling to or unable to comply with the protocol, or who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study. * Prior treatment with a MEK inhibitor of any kind

Study Objectives The purpose of this study is to find out if panobinostat taken with cisplatin and pemetrexed can be used safely without increasing side effects and that the combination will have a better effect than platinum-based doublet chemotherapy alone. Conditions: Solid Tumors, Non-Small Cell Lung Cancer (NSCLC) Intervention / Treatment: DRUG: Panobinostat, Cisplatin, Pemetrexed 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: * Histological or cytological proven advanced solid tumors for which curative standard treatments are not available. * Must have measurable or evaluable disease. * Male or female patients aged >= 18 years old. * Any number of prior chemotherapy regimens. * ECOG Performance Status of <= 2 with a life expectancy greater than 3 months. * Clinically euthyroid (may be on thyroid hormone replacement) * Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of study treatment. * Ability to provide written informed consent * Must meet the following laboratory criteria: Hematology: * Neutrophil count of >= 1.5 x 109/L * Platelet count of >= 100 x 109/L * Hemoglobin >= 9 g/dL Biochemistry: * AST/SGOT and ALT/SGPT <= 2.5 x upper limit of normal (ULN) or <= 5.0 x ULN if the transaminase elevation is due to disease involvement * Serum bilirubin <= 1.5 x ULN * Serum creatinine <= 1.5 x ULN or 24-hour creatinine clearance >= 50 ml/min * Total serum calcium (corrected for serum albumin) or ionized calcium >= LLN and <= ULN * Serum potassium >= LLN and <= ULN * Serum sodium >= LLN and <= ULN * Serum albumin >= LLN or 3g/dl * Serum magnesium >= LLN and <= ULN * Any elevated Alkaline Phosphatase due to bone metastasis can be enrolled Exclusion Criteria: * Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer. * Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment. * Patients who have received chemotherapy, any investigational drug or undergone major surgery < 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy. * Impaired cardiac function * Other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol * Concomitant use of drugs which are generally recognized to have a risk of causing torsades de pointes where such treatment cannot be discontinued or switched to a different medication prior to starting study drug * Patients with unresolved diarrhea >= CTCAE grade 2 * Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat. Inability to swallow panobinostat capsules whole. * Concomitant use of any anti-cancer therapy or radiation therapy * Uncontrolled or symptomatic brain metastases. * Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not willing to use a double barrier method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a barrier method. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). * Male patients whose sexual partners are WOCBP not using a double method of contraception during the study and 3 months after the end of treatment. * Known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required * Any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent

Study Objectives This research study is evaluating a drug called buparlisib (BKM120) as a possible treatment for locally advanced head and neck squamous cell cancer. Conditions: Carcinoma, Squamous Cell of Head and Neck, HPV Positive Oropharyngeal Squamous Cell Carcinoma, Hypopharyngeal Cancer, Early Invasive Cervical Squamous Cell Carcinoma, Carcinoma of Larynx, Cancer of Nasopharynx Intervention / Treatment: DRUG: BKM120, DRUG: Cisplatin, RADIATION: Intensity-modulated radiotherapy (IMRT) 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/IV, locally advanced, biopsy proven squamous cell cancer of the head and neck that undergo chemoradiation as their primary treatment with curative intent. * Oropharynx (HPV positive and HPV negative), hypopharynx, larynx primaries, nasopharynx as well as those with documented SCC of the cervical lymph nodes, with unknown primaries. * >10 pack years of tobacco use * Age >= 18 years * ECOG performance status <= 2 * At least one site of measurable disease * Adequate bone marrow function as shown by: ANC > 1.5 x 109/L, Platelets >100 x 109/L, Hb >9 g/dL * Total calcium (corrected for serum albumin) within normal limits * Magnesium >= the lower limit of normal * Potassium within normal limits for the institution. * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range * Serum bilirubin within normal range (or <= 1.5 x 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) * Serum creatinine <= 1.5 x ULN or 24-hour clearance >= 50 mL/min * Serum amylase <= ULN * Serum lipase <= ULN * Fasting plasma glucose <= 120 mg/dL (6.7 mmol/L) * Signed informed consent * INR <= 2 Exclusion Criteria: * Distant metastatic disease * Less than or equal to 10 pack years of tobacco history * Received prior chemotherapy * Received prior radiation to the head and neck or adjacent anatomical site * Received prior treatment with a P13K inhibitor. * Known hypersensitivity to BKM120 or to its excipients * Acute or chronic liver, renal disease or pancreatitis * Mood disorders >= CTCAE grade 3 * Diarrhea >= CTCAE grade 2 * Active cardiac disease * History of cardiac dysfunction including any of the following: * Patient has poorly * Impairment of gastrointestinal (GI) function * Currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug. * Chronic treatment with steroids or another immunosuppressive agent. * Herbal medications and certain fruits within 7 days prior to starting study drug. * Currently treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. Please refer to Appendix B for a list of prohibited inhibitors and inducers of CYP3A (Please note that co-treatment with weak inhibitors of CYP3A is allowed). * Undergone major surgery <= 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy. * Currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant. * Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control. * Known diagnosis of human immunodeficiency virus (HIV) infection * History of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix

Study Objectives This was a retrospective cohort study using the PharMetrics database. The analysis was conducted using the most recent 5 years of data from the database, January 1, 2015, to October 30, 2020. Included patients were followed for outcome evaluation from the index date (first prescription of treatment, immunotherapy \[IO\], or targeted therapy \[TT\] following diagnosis of non-metastatic malignant melanoma and evidence of first lymph node resection), until the first occurrence or end of continuous eligibility or end of the study period. Conditions: Melanoma Intervention / Treatment: DRUG: Nivolumab, DRUG: Ipilimumab + nivolumab, DRUG: Pembrolizumab, DRUG: Dabrafenib + trametinib Location: United States Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria * Patients with at least one diagnosis of malignant melanoma of skin anytime from the start of data collection until the start of study period. * Patients with a procedure of first lymph node dissection or nodal basin ultrasound surveillance, per the National Comprehensive Cancer Network (NCCN) guidelines version 2.2020. The first lymph node dissection / nodal basin ultrasound surveillance signified that the patient was eligible to receive systemic treatment as adjuvant therapy. * The first lymph node dissection or nodal basin ultrasound surveillance (index adjuvant date) must have had a diagnosis of malignant melanoma of skin within 6 months, to ensure that the dissection was related to melanoma. * Patients with at least pharmacy or medical claim for the study drugs within 1 year on and after index date. The index date was the date of first prescription of study drug, IO (i.e., nivolumab, ipilimumab + nivolumab, pembrolizumab) or dabrafenib + trametinib. * At least 18 years of age at the time of adjuvant treatment initiation. * Patients with at least 6 months of continuous enrollment prior to the index date. * Patients with at least 6 months of continuous enrollment after the index date. * If necessary, there were additional criteria of absence of secondary malignancy (including metastatic site). Exclusion Criteria * Patients with a diagnosis of non-melanoma primary malignancy during the 6 months pre-index period. * Patients with chemotherapy or interferon alpha before index date. * Patients with pregnancy any time during the study period.

Study Objectives This study will evaluate the safety, efficacy, pharmacokinetics and immunogenicity of induction treatment consisting of atezolizumab in combination with obinutuzumab plus lenalidomide in patients with relapsed or refractory follicular lymphoma (FL), followed by maintenance treatment with atezolizumab plus obinutzumab plus lenalidomide in patients who achieve a complete response (CR), a partial response (PR), or stable disease at end of induction. Conditions: Lymphoma, Follicular Intervention / Treatment: DRUG: Atezolizumab (MPDL3280A) [TECENTRIQ], DRUG: Lenalidomide, DRUG: Obinutuzumab Location: United States, France Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 * Relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator * Histologically documented CD20-positive lymphoma as determined by the local laboratory * Fluorodeoxyglucose-avid lymphoma (i.e., PET-positive lymphoma) * At least one bi-dimensionally measurable lesion (>1.5 cm in its largest dimension by CT scan or magnetic resonance imaging [MRI]) * Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL * Agreement to comply with all local requirements of the lenalidomide risk minimization plan * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of <1% per year, for at least 28 days prior to Day 1 of Cycle 1, during the treatment period (including periods of treatment interruption), and for at least 18 months after the last dose of study treatment * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm for at least 3 months after the last dose of study treatment Exclusion Criteria: * Grade 3b follicular lymphoma * History of transformation of indolent disease to diffuse large B-cell lymphoma (DLBCL) * Known CD20-negative status at relapse or progression * Central nervous system lymphoma or leptomeningeal infiltration * Prior allogeneic stem-cell transplantation (SCT) * Completion of autologous SCT within 100 days prior to Day (D) 1 of Cycle (C) 1 * Prior standard or investigational anti-cancer therapy as specified in protocol * History of resistance to lenalidomide or response duration of <1 year * Treatment with systemic immunosuppressive medications * History of solid organ transplantation * Clinically significant toxicity from prior therapy that has not resolved to Grade <=2 (according to the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE], v4.0) prior to Day 1 of Cycle 1 * History of erythema multiforme, Grade >= 3 rash, or blistering following prior treatment with immunomodulatory derivatives such as thalidomide and lenalidomide * Active bacterial, viral, fungal, or other infection * Positive for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at screening * Known history of HIV positive status * History of progressive multifocal leukoencephalopathy * History of autoimmune disease * Contraindication to treatment for TE prophylaxis * Grade <= 2 neuropathy * History of other malignancy that could affect compliance with the protocol or interpretation of results * Evidence of any significant, uncontrolled concomitant disease * Inadequate hematologic function (unless due to underlying lymphoma) * Abnormal laboratory values (unless due to underlying lymphoma) * Pregnant or lactating or intending to become pregnant during the study

Study Objectives The purpose of this study is to find out if patients older than 60, with acute myeloid leukemia, who are in complete remission following initial chemotherapy, will live longer and have a lower rate of leukemia relapse when treated with azacitidine. Conditions: Leukemia Intervention / Treatment: DRUG: Azacitidine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologic or cytologic confirmation of AML with greater than 20% blasts in bone marrow. All AML subtypes of the World Health Organization (WHO) classification will be included with the exception of promyelocytic leukemia and cytogenetics showing the (15;17) translocation or AML secondary to chemotherapy. * Achieved first morphologic complete remission (CR) or first morphologic complete remission with incomplete platelet recovery (CRp) after completion of induction chemotherapy using a standard induction regimen. Up to 2 induction cycles will be allowed. Confirmation of CR is defined as < 5% blasts in the bone marrow specimen, with a count of at least 100-200 nucleated cells and absence of Auer rods, along with peripheral blood neutrophil count >1.0 x 10^9/L and platelet count >100 x 10^9/L. Confirmation of CRp is defined as <5% blasts in the bone marrow specimen, with a count of at least 100-200 nucleated cells and absence of Auer rods, with incomplete platelet recovery (ANC >= 1000/µL and platelets 50-99,000/µL, along with transfusion-independence of red blood cells). * Received up to 2 cycles of any consolidation chemotherapy * Have an Eastern Cooperative Oncology Group (ECOG) performance status <=2 * Normal organ function at the time of screening: Total bilirubin <=1.5 x upper limit of normal (ULN); aspartic transaminase (AST) and alanine transaminase (ALT) <=2.5 x ULN; Serum creatinine <=1.5 x ULN or creatinine clearance >60 mL/min for patients with creatinine levels above ULN * Men must agree to avoid fathering a child throughout the study. * Be capable of giving informed consent and have signed the informed consent form (ICF) Exclusion Criteria: * Greater than 12 weeks since initiation of most recent cycle of consolidation chemotherapy * Women of childbearing potential * Prior relapse after complete remission for AML * AML secondary to previous exposure to cytotoxic chemotherapy known to induce leukemia * Active malignancy other than AML * Any diagnosis of metastatic disease * Have hepatic tumors * Radiation therapy, chemotherapy, or cytotoxic therapy, given to treat conditions other than AML <4 weeks prior to Day 1 or have not recovered from adverse events due to agents administered >4 weeks earlier * Known leukemic involvement of the central nervous system * Known or suspected hypersensitivity to azacitidine or mannitol * Prior or active disease that, in the opinion of the Investigator, may interfere with the procedures or evaluations to be conducted in the study (uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements) * Active viral infection with known human immunodeficiency virus (HIV) or viral hepatitis type B or C * Treatment with other investigational drugs within the 30 days prior to Day 1, or ongoing adverse events from previous treatment with investigational drugs, regardless of the time period * Any prior treatment with azacitidine or decitabine

Study Objectives The purpose of this study is to assess safety and efficacy of brentuximab vedotin in combination with bendamustine in patients with relapsed or refractory Hodgkin lymphoma. It is an open-label, 2-stage study designed to determine the recommended dose level of bendamustine in combination with brentuximab vedotin. The study will assess the safety profile of the combination treatment and determine what proportion of patients achieve a complete remission. Conditions: Hodgkin Disease Intervention / Treatment: DRUG: brentuximab vedotin, DRUG: bendamustine Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histopathological diagnosis of classical Hodgkin lymphoma * Failed standard front-line therapy * Measurable disease of at least 1.5 cm as documented by radiographic technique * Eastern Cooperative Oncology Group performance status less than or equal to 2 Exclusion Criteria: * Received prior salvage therapy, including radiotherapy * Chemotherapy, radiotherapy, biologics, and/or other treatment with immunotherapy not completed 4 weeks prior to first dose of study drug * Concurrent use of other investigational agents

Study Objectives This clinical trial is designed to study whether docetaxel (Taxotere) helps reduce the risk of relapse in patients with prostate cancer who have had their prostate removed by surgery, but are at high risk of their cancer recurring. During the trial, doctors will also closely monitor patients for side effects of the chemotherapy. Docetaxel is a chemotherapy drug that prevents tumor cells from dividing, so they stop growing or die. Doctors use docetaxel to treat lung and breast cancer, and studies show it can help shrink tumors in some patients with prostate cancer that has spread to other parts of their bodies. The researchers conducting this study want to determine if docetaxel also helps reduce the likelihood of prostate cancer returning after surgery has removed the original tumor. All of the study participants will receive up to 18 doses of docetaxel, each administered through a needle inserted into a vein. Each round of treatment will consist of 30-minute, weekly infusions for three consecutive weeks, followed by one week with no chemotherapy. Before and after the chemotherapy, patients will take dexamethasone, an oral steroid that reduces the risk of an allergic reaction to the medication. If the side effects of the treatment become too intense, doctors may modify, delay, or even stop chemotherapy during the trial. Conditions: Prostate Cancer Intervention / Treatment: DRUG: Docetaxel Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

INCLUSION CRITERIA: * patients with prostate cancer who have just undergone prostatectomy, * high risk of their cancer recurring (High risk is defined as at least a 50 percent chance the cancer will return within three years after surgery.) EXCLUSION CRITERIA: * Prior systemic treatment for prostate cancer with hormonal therapy, chemotherapy, or any other anticancer therapy. * Prior radiation therapy * Patients receiving any concurrent therapy for cancer. This includes alternative therapies * Patients requiring concurrent treatment with corticosteroids, with the exception of inhaled and topical corticosteroids. * History of a malignancy other than prostate cancer * Peripheral neuropathy >= Grade 2 * Psychological, familial, sociological or geographical conditions which do not permit treatment and/or medical follow-up required to comply with the study protocol * Patients with a history of hypersensitivity reaction to products containing Polysorbate 80 (Tween 80).

Study Objectives Trial objectives: The primary objective is to determine the proportion of patients who have 50% decrease in PSA maintained for at least 4 weeks, in advanced hormone-refractory prostate cancer (HRPC) patients who receive thalidomide (100 mg BID). Secondary objectives include the objective tumor response rate for measurable lesions, the median duration of tumor response, median time to disease progression and assessments of clinical benefits, quality of life, and safety profile. Conditions: Hormone-refractory Prostate Cancer Intervention / Treatment: DRUG: Thalidomide (THADO) Location: Taiwan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * 18 years of age or older. * Histologically or cytologically confirmed adenocarcinoma of prostate that is metastatic, hormone-refractory (confirmed by testing serum testosterone), and clinically progressive following at least one prior hormonal regimen. * Patients must have documented progression of disease on anti-androgen withdrawal, if the patient have documented progression on previous anti-androgen therapy. * Measurable (patient with measurable bi-dimensional disease) or evaluable disease (defined as the presence of a nonmeasurable abnormality on CT or on physical examination coupled with a PSA ³ 30). * Karnofsky performance status ³ 60%.6. Adequate bone marrow functions: Granulocyte count 1,000/mm3, Platelets 75,000/mm3, haemoglobin 8 g/dl. * Adequate renal and liver functions: Creatinine < 1.5 mg/dl, Bilirubin < 2 mg/dl, ALT/AST less than 2.5 times the upper limit of the reference range for the institute. * Patients with chemical or clinical hypothyroidism should have their thyroid replacement prior to starting study. * Patients must have recovered from the effect of recent surgery (at least 4 weeks apart), radiotherapy (at least 4 weeks apart). * Patients have ability to complete Quality of Life (QoL) questionnaires. * Patients must sign informed consent. Exclusion Criteria: * Patients with advanced second primary malignancy. * Patients with brain metastases. * Patients with hypersensitivity to thalidomide. * History of myocardial infarction within past 6 months, uncontrolled congestive heart failure or angina pectoris. * Patients with orthostatic hypotension before therapy. * Patients with NCI CTC grade 3 or greater peripheral neuropathy of any cause that is clinically detectable. * Patients with active infection, including positive serology for HIV. * Patients who have received chemotherapy before for treatment of metastases of prostate cancer, or received other investigational agents or corticosteroids within 4 weeks prior to enrollment of study.

Study Objectives The role of micronutrients in fertility has recently gained increased attention. In women who suffer from polycystic ovary syndrome (PCOS) and infertility, we aim to test the impact of a standardized, multinutrient supplementation on the course of PCOS-specific parameters namely anti-Mullerian hormone (AMH), testosterone, and androstenedione. A total of 60 infertile women with PCOS, previously untreated, will be randomized to receive either a combined standardized multinutrient supplementation (containing folic acid, selenium, vitamin E, catechins, glycyrrhizin, coenzyme Q10 and omega-3-fatty acids; study group) or folic acid alone (control group) in a double-blinded, randomized manner. These study medications will be provided for 3 months and pre- to posttreatment levels of AMH, testosterone, and AMH will be analysed. The study will be performed at the Clinical Division of Gynecologic Endocrinology and Reproductive Medicine of the Medical University of Vienna. Conditions: Polycystic Ovary Syndrome, Infertility, Female, Micronutrient Deficiency Intervention / Treatment: DIETARY_SUPPLEMENT: Profertil female, DIETARY_SUPPLEMENT: Folic acid 400 mg Location: Austria Study Design and Phases Study Type: INTERVENTIONAL Phase: NA Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * The patient has been diagnosed with PCO-syndrome using revised 2004 Rotterdam-criteria (7). * The patient is sterile, defined as being unable to become pregnant within a year despite unprotected sexual intercourse. * The patient suffers either from oligomenorrhoea (defined as an interval of >=60 days between the last three menstruations) or complete amenorrhoea for at least 90 days. * The patient has given her written informed consent after detailed information on the study by medical professionals at the Department of Obstetrics and Gynecology of the Medical University of Vienna. * Both partners are at least 19 years old and are younger than 35. The age limit was chosen to take physiologically reduced fertility beyond this age (8). This measure allowed the women to avoid a 100-day delay of fertility treatments due to this study. Exclusion Criteria: * No informed consent. * At least one partner is younger than >= 19 years than 35 years. * The patient has been subject to one of the following PCO-syndrome-related treatments within three months before inclusion: metformin, combined oral contraceptives, cortisol therapy, inositol, ovarian drilling, any kind of ovarian stimulation, in-vitro fertilisation. Promoting menstruation using gestagen products is acceptable.

Study Objectives This study proposes to determine the safety of the administration of E7820 plus cetuximab and explore the MTD of the combination in a Phase Ib study. In addition, the efficacy of this combination will be explored in patients with colorectal cancer in the Phase II proof of concept phase of the study. Conditions: Advanced Colorectal Cancer Intervention / Treatment: DRUG: E7820 plus cetuximab Location: United States, Canada Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * For Phase Ib, patients must have a histologically or cytologically confirmed malignant solid tumor for which no effective therapy is available or the patient must not be a candidate for standard therapy. * For Phase II, patients must have a pathologically and histologically documented colorectal carcinoma that is inoperable and/or metastatic. These patients must also have at least one unidimensional measurable lesion according to the RECIST guidelines. * Patients must have an ECOG Performance Status of 0-1. * Patients must have a life expectancy of >= 3 months. * Patients must be aged >= 18 years. * Patients must have adequate renal function as evidenced by serum creatinine < 2 mg/dL and creatinine clearance > 40 mL/minute. * Patients must have adequate bone marrow function as evidenced by ANC >= 1,500 /mm3 and platelets >= 100,000 /mm3. * Patients must have adequate hepatic function as evidenced by liver function test abnormalities no greater than CTC grade 1 (bilirubin, alanine transaminase [ALT], and aspartate transaminase [AST]) unless increased LFTs are related to liver metastases in which case CTC grade 2 abnormalities acceptable. * Patients must be willing and able to comply with the study protocol for the duration of the study. * 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. * Patients may have received prior bevacizumab therapy as long as therapy has been discontinued for 4 weeks or longer. Exclusion Criteria: * Patients who have a history of previous Grade 2 or higher hypersensitivity to sulfonamide derivatives. * Patients previously treated with cetuximab, or who have received prior treatment with any EGFR-related cancer therapy, either an approved or investigational agent. * Patients with known sensitivity to murine monoclonal antibodies. * Patients who have had radiation to >= 25% of their bone marrow (e.g., pelvic radiation) within 4 weeks prior to E7820 treatment. * Patients who have not recovered from any clinically significant (Grade 3 or 4) chemotherapy, immunotherapy, or radiotherapy related toxicity at study entry (excluding neuropathy, infertility, or alopecia). * Patients who have received investigational drugs or any other anti-neoplastic therapy within 28 days of E7820 treatment. * Patients who have had major surgery within 4 weeks of study drug administration. * Women who are pregnant or breast-feeding. Women of childbearing potential with either a positive pregnancy test at screening or no pregnancy test. Women of childbearing potential unless using adequate measures of contraception in the opinion of the Investigator (postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential). * Fertile men and fertile women who are not willing to use contraception or fertile men or fertile women with a partner who is not willing to use contraception. * Patients with brain or subdural metastases are not eligible except if they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least one month before starting treatment with E7820. Any signs (eg, radiologic) and/or symptoms from their brain metastases must be stable for at least one month. * Patients who have a positive history of human immunodeficiency virus, hepatitis B or active hepatitis C. * Patients with severe uncontrolled intercurrent illness/infection (excluding malignancies). * Patients with a history of unstable ischemic cardiac disease or more than Class II NYHA heart failure. * Patients with a history of clinically significant arterial thrombosis or who have taken therapeutic doses of anticoagulants within the last 7 days. * Patients who have pulmonary disease that puts them at risk of hemoptysis or bleeding diathesis. Head and neck cancer patients at risk for major vessel bleeding. * Patients receiving therapeutics doses of anticoagulants. * Patients with poorly controlled type I insulin-dependent diabetes or poorly-controlled type II insulin-dependent diabetes or a fasting blood glucose >10 mmol/L (200 mg/dL). * Patients with significant comorbid disease or condition, which in the Investigator's opinion would exclude the patient from the study.

Study Objectives This phase II study will evaluate the effect of bevacizumab, capecitabine and oxaliplatin with radiation on rectal cancer. Researchers will also evaluate the tolerability (how it makes the patient feel) and safety of this combination by watching for harmful side-effects.It is hoped that by adding bevacizumab to the capecitabine/oxaliplatin treatment in combination with radiation before surgery will improve response rate. Conditions: Advanced Colorectal Cancer Intervention / Treatment: DRUG: Bevacizumab: Location: 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 confirmed adenocarcinoma of the rectum, defined as either: Mid- or upper rectal tumours (>= 6 - 15 cm): T3 or T4 adenocarcinoma that is fixed or partially fixed or tethered and is potentially resectable; or Low rectal tumours (<6cm): T3 or T4 adenocarcinoma: or Node positive rectal tumours (<= 15cm): T1-4N2 or T1-4N+ where pelvic nodes approach or invade the mesorectum. M0/X or M1 is permitted as long as definitive resection of the primary tumour is planned and, in the opinion of the investigator, it is safe to delay full dose of systemic chemotherapy * Appropriate staging investigations of the primary tumour, either endorectal ultrasound or pelvic MRI. * Male or female aged >= 18 years. * Have a performance status ECOG of 0 or 1. * Have a life expectancy greater than 6 months. * Adequate organ function and coagulation parameters as measured by: ANC >=1.5 platelets >=100 Serum creatinine <= 1.5X ULN AST, ALT <= 2.5X ULN Bilirubin <= 1.5 ULN PTT and INR within normal limits Albumin >= than 30 * Patient consent * No neurological diseases that can increase the neurotoxicity of oxaliplatin * Be willing and able to comply with the protocol for the duration of the study. Exclusion Criteria: * Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day -14, (i.e. patients must have recovered from any major surgery), or anticipation of need for major surgical procedure during or within 7 weeks after chemo-radiotherapy. * Known to have clinical or radiological evidence of CNS metastases. * Patients with a past or current history (within last 2 years) of other malignancies, except for the indication under this study and curatively treated basal and squamous skin cancer or in-situ cancer of the cervix. * Women of childbearing potential with either a positive or no pregnancy test at baseline or lactating. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. * Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study. Patients of childbearing potential must be willing to use a reliable method of birth control. i.e.: doublebarrier method, oral contraceptive, implant, dermal contraception, long-term injectable contraceptive, intrauterine device or tubal ligation during the study * Evidence of bleeding diathesis or coagulopathy. * Uncontrolled hypertension, defined as SBP > 150/100 on more than one occasion that does not respond to therapy with antihypertensive agents * Clinically significant (i.e. active) cardiovascular disease for example: cerebrovascular accidents (<=6 months), myocardial infarction (<= 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication. * Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes i.e. except for anticoagulation for maintenance of patency of permanent indwelling IV catheters. * Evidence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or puts the patient at high risk from treatment complications. * Ongoing treatment with aspirin (> 325 mg/day) or other medications known to predispose to gastrointestinal ulceration. * Any other serious or uncontrolled illnesses. * Current or recent serious polyneuropathy. * Known hypersensitivity against bevacizumab. * Known peripheral neuropathy >= NCI CTCAE grade 1. Absence of deep tendon reflexes (DTRs) as the sole neurologic abnormality does not render the patient ineligible. * Organ allografts requiring immunosuppressive therapy. * Serious, non-healing wound, ulcer, or bone fracture.

Study Objectives This phase II trial studies how well lenvatinib works in treating patients with pheochromocytoma or paraganglioma that has spread to other places in the body or cannot be removed by surgery. Lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Conditions: Malignant Adrenal Gland Pheochromocytoma, Malignant Paraganglioma, Metastatic Adrenal Gland Pheochromocytoma Intervention / Treatment: OTHER: Laboratory Biomarker Analysis, DRUG: Lenvatinib, OTHER: Quality-of-Life Assessment Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Histologically or cytologically confirmed malignant secretory or non-secretory pheochromocytoma or paraganglioma that is unresectable and deemed inappropriate for alternative local regional therapeutic approaches * Measurable disease * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 * Life expectancy > 24 weeks * Absolute neutrophil count (ANC) >= 1500/mm^3 * White blood cell (WBC) count >= 3,000/mm^3 * Platelet count >= 100,000/mm^3 * Hemoglobin >= 9.0 g/dL (5.6 mmol/L); NOTE: transfusions are not allowed =< 7 days prior to registration * Total bilirubin =< 1.5 X upper limit of normal (ULN) (or total bilirubin =< 3.0 X ULN with direct bilirubin =< 1.5 X ULN in patients with well-documented Gilbert's Syndrome) * Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 X ULN * Creatinine =< 1.5 x ULN * Urine protein/creatinine ratio =< 1 OR 24-hour urine protein < 1.5 gram * Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only * Blood pressure (BP) < 150 mmHg (systolic) and < 90 mmHg (diastolic); initiation or adjustment of BP medication is permitted prior to registration provided that the average of three BP readings at a visit prior to registration is < 150/90 mmHg; NOTE: all patients with secretory pheochromocytoma or paraganglioma are REQUIRED to: 1) be evaluated in consultation by a hypertension specialist with specific experience in the management of hypertension in the setting of catecholamine-secreting tumors (usually an endocrinologist, nephrologist, or a cardiologist), and in the setting of hormone-associated hypertension) receive alpha- and beta-adrenergic blockade for at least 7-14 days prior to initiation of lenvatinib; the hypertension specialist of record for each patient should be committed to closely following the patient during the clinical study with evaluation by said specialist required at cycle 1 and 2 and thereafter on an as needed basis * Provide written informed consent * Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study) * Ability to complete questionnaire(s) by themselves or with assistance Exclusion Criteria: * Any of the following: * Pregnant women * Nursing women * Men or women of childbearing potential who are unwilling to employ adequate contraception * Chemotherapy/systemic therapy, radiotherapy, immunotherapy or surgery =< 21 days prior to registration or kinase inhibitor therapy =< 14 days prior to registration or failure to recover from toxicities (to grade 1 or below) from treatment; NOTE: concurrent therapy with octreotide is allowed providing that tumor progression on this therapy has been demonstrated; concurrent therapy with bisphosphonates (e.g. zoledronic acid) or denosumab is also allowed; NOTE: an unlimited number of prior chemotherapeutic or biologic therapies for malignant pheochromocytoma or paraganglioma is permitted; this includes prior anti-angiogenesis therapies such as tyrosine kinase inhibitors * Active or uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Receiving any other investigational agent * Current use of warfarin for any reason; NOTE: if patient can be safely transitioned to another anticoagulant, they may be eligible provided other criteria are satisfied * Any of the following: * Correct QT (QTc) prolongation (defined as a QTc interval >= 500 msecs) * Left ventricular ejection fraction (LVEF) < institutional lower limits of normal (LLN) * Frequent ventricular ectopy * Evidence of ongoing myocardial ischemia * Receiving any medications or substances with risk of torsades de pointes; NOTE: medications or substances with known risk of torsades de pointes are prohibited; consult pharmacist for review if needed * Known active and/or untreated brain metastases * Known severe allergic or other prohibitive reactions to other tyrosine kinase inhibitors (TKI) * Prior treatment with lenvatinib * Any of the following conditions: * Active peptic ulcer disease * Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions which increase the risk of perforation * History of new abdominal fistula, gastrointestinal perforation or intra-abdominal abscess =< 84 days prior to registration; NOTE: enrollment of patients with chronic/canalized fistulous tracts (present for > 84 days) is allowed * Serious or non-healing wound, ulcer, or bone fracture * History of familial QTc prolongation syndrome * Any of the following conditions =< 6 months prior to registration: * Cerebrovascular accident (CVA) or transient ischemic attack (TIA) * Serious or unstable cardiac arrhythmia * Admission for unstable angina or myocardial infarction * Cardiac angioplasty or stenting * Coronary artery bypass graft surgery * Pulmonary embolism, untreated deep venous thrombosis (DVT) or DVT which has been treated with therapeutic anticoagulation =< 30 days * Arterial thrombosis * Symptomatic peripheral vascular disease * Other active malignancy =< 2 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 for their cancer; NOTE: adjuvant anti-estrogen/hormonal therapy for breast cancer is allowed

Study Objectives A prospective, double blinded and randomized study included women with breast cancer and underwent mastectomy, and randomly allocated into two groups of equal size. Lidocaine group and control group. Conditions: Cancer, Breast Intervention / Treatment: DRUG: Lidocaine, DRUG: Normal saline Location: Egypt Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: PREVENTION Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: QUADRUPLE

Inclusion Criteria: * Women aged between 18 and 60 years old with breast cancer and underwent mastectomy, American society of Anesthesiologist I or II Exclusion Criteria: * Patients with contralateral breast cancer, metastatic tumor, morbid obesity (BMI> 40), allergy to an amide local anesthetic, or morphine sulphate, heart block, renal, or liver dysfunction, or substance abuse disorder, or chronic opioid use

Study Objectives Anthracycline-containing regimens are recommended as adjuvant treatment for women with node positive breast cancer. In at least three large randomized clinical trials the addition or sequential administration of a taxane (paclitaxel or docetaxel) to an antracycline-based regimen resulted in superior clinical outcome for women with node positive early breast cancer. In two large randomized studies the dose dense administration with G-CSF support of anthracycline-based and paclitaxel combination was superior to the same regimen administered every three weeks without growth factors as adjuvant therapy in women with axillary node positive breast cancer. In one randomized trial, docetaxel was proved superior to paclitaxel in women with metastatic breast cancer Conditions: Breast Cancer Intervention / Treatment: DRUG: Docetaxel, DRUG: Paclitaxel, DRUG: Epirubicin, DRUG: Cyclophosphamide, DRUG: 5-fluoruracil, DRUG: Granulocyte-colony stimulating growth factor Location: Greece Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: NONE

Inclusion Criteria: * Women with histologically-confirmed unilateral invasive ductal or lobular breast adenocarcinoma * Within 60 days after the surgical excision of the primary tumor with tumor-free operation margins; at least 10 axillary lymph nodes have to be removed. * Tumor involvement of at least one axillary lymph node * Absence of any clinical or radiological evidence of local or metastatic disease * Premenopausal or postmenopausal women aged 18-75 years old * Adequate bone marrow function (absolute neutrophil count >1500/mm3, platelet count >100.000/mm3, hemoglobin >10gr/mm3) * Adequate liver (bilirubin <1.0 times upper limit of normal and SGOT/SGPT <2.5 times upper limit of normal) and renal function (creatinine <1.5mg/dl) * Adequate cardiac function (LVEF>50%) * Written informed consent Exclusion Criteria: * Positive pregnancy test. * Psychiatric illness or social situation that would preclude study compliance. * Other concurrent uncontrolled illness. * Prior or concurrent antineoplastic therapy e.g. hormonal therapy, radiation therapy, chemotherapy, biological agents. * Previous history of other invasive malignancy other than non-melanomatous skin cancer.

Study Objectives The purpose of this research study is to get information from volunteers without cancer and patients with cancer who have received a new investigational study agent called, "\[F-18\] RGDK5," to evaluate biodistribution and dosimetry for the study agent and determine F-18 RGD-K5 uptake in angiogenic tumor. the system. Conditions: Sarcoma, Melanoma, Lung Cancer, Breast Cancer, High Grade Gliomas Intervention / Treatment: DRUG: F-18 RGD-K5 Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: EARLY_PHASE1 Primary Purpose: DIAGNOSTIC Allocation: NON_RANDOMIZED Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: For Normal Volunteers * Subject is >= 18 years old at the time of investigational product administration (Subject is male or female of any race / ethnicity) * Subject or subject's legally acceptable representative provides informed consent * Subject is capable of complying with study procedures * Subject is capable of communicating with study personnel For Cancer Subjects (same first four bullets as 'normals') * Subject must have had a diagnostic imaging study and is suspected of having a primary or metastatic tumor(s) ( > 2 cm, except breast tumor)-sarcoma; melanoma; lung cancer [including small cell and non-small cell lung cancer (NSCL)]; high grade glioma (including glioblastoma multi-forms), anaplastic astrocytoma, and anaplastic oligodendroglioma; breast carcinomas, and head and neck tumors, including laryngeal squamous cell carcinoma * Subject is scheduled to have a clinical [F-18]FDG PET scan within ± 7 days (with no interventions between the two PET scans) of the investigational, [F-18]RGD-K5 PET scan * Subject is scheduled to undergo resection or biopsy of the target tumor as a result of routine clinical treatment * Subject has not received any anti-angiogenic agents (e.g. bevacizumab, sorafenib, sunitinib) within 10 days prior to PET/CT imaging * Subject has laboratory test results within the following ranges: * AST(SGOT)/ALT(SGPT) <= 2.5 x institutional upper limits of normal * Serum creatinine <= 1.5 institutional upper limits of normal * Platelet count of > 75,000x106/L * Hemoglobin value of > 9 g/dL * ANC > 1.2 x 106 /mL Exclusion Criteria 'Normals': * Subject is < 18 at the time of investigational product administration * Female subject is pregnant or nursing: * by testing on site at the institution (serum or urine ßHCG) within 24 hours prior to the investigational product administration * Subject is unable to remain still for duration of imaging procedure * Subject has a history of renal disease * Subject has previously received [F-18]RGD-K5 at any time, or any other investigational product in the past 30 days or will receive any other investigational product within 48 hours after the [F-18]RGD-K5 injection * Subject has not been involved in an investigative, radioactive research procedure or therapeutic procedure within the past 6 months * Subject has any other condition or personal circumstance including severe claustrophobia, severe dyspnea, severe back pain etc, that, in the judgment of the investigator, might interfere with the collection of complete good quality data * Subject has a history of significant prescription or non-prescription drug, or alcohol abuse, including but not limited to marijuana, cocaine, heroin or derivatives. For Cancer Subjects (first three bullets the same as 'normals') * Subject is < 18 at the time of investigational product administration * Female subject is pregnant or nursing: * by testing on site at the institution (serum or urine ßHCG) * Subject is unable to remain still for duration of imaging procedure * Subject has known hyper or hypo-coagulation syndromes. (e.g., Protein C, S deficiency, Hemophilia A/B/C, Factor-V Leiden, etc.) * Subject has previously received [F-18]RGD-K5 at any time, or any other investigational product in the past 30 days or will receive any other investigational product within 48 hours after the [F-18]RGD-K5 injection. * Subject has inadequate tumor size (< 2 cm , except for breast tumor) or volume to allow for biopsy * Subject has any other condition or personal circumstance including severe claustrophobia, severe dyspnea, severe back pain etc, that, in the judgment of the investigator, might interfere with the collection of complete good quality data * Subject has a history of significant prescription or non-prescription drug, or alcohol abuse, including but not limited to marijuana, cocaine, heroin or derivatives.

Study Objectives The purpose of this study is to reduce the side-effects from anti-leukemia therapy. The therapy in this study is based upon treatment information learned from prior clinical research programs as well as from laboratory research. Conditions: Acute Lymphoblastic Leukemia Intervention / Treatment: DRUG: prednisone, DRUG: dexamethasone, DRUG: doxorubicin, DRUG: E. coli asparaginase, DRUG: vincristine, DRUG: methotrexate, DRUG: Leucovorin, DRUG: Asparaginase, DRUG: cytarabine, DRUG: Methotrexate/Hydrocortisone 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 lymphoblastic leukemia excluding known mature B-cell ALL by the presence of any of the following: surface immunoglobulin, L3 morphology, t(8;14) (q24;q32), t(8;22) or t(2;8) * Age > 12 months but less than 18 years Exclusion Criteria: * Prior therapy except, 1 week of steroids, or emergent radiation therapy to the mediastinum * Known HIV positive

Study Objectives RATIONALE: Methylphenidate may help relieve fatigue caused by cancer. It is not yet known whether methylphenidate is more effective than a placebo in relieving fatigue and improving quality of life in patients with cancer. PURPOSE: This randomized phase III trial is studying methylphenidate to see how well it works in treating patients with fatigue caused by cancer. Conditions: Fatigue, Unspecified Adult Solid Tumor, Protocol Specific Intervention / Treatment: DRUG: methylphenidate hydrochloride, OTHER: placebo Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: SUPPORTIVE_CARE Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: DOUBLE

Inclusion Criteria: * >= 18 years of age * Men or women with a history of cancer-related fatigue as defined by a score >= 4 on a fatigue numerical analogue scale (0 - 10) * Fatigue for >= 1 month prior to registration * ECOG Performance Score (PS) 0, 1, or 2 * Life expectancy >= 6 months * Histologic or cytologic proven cancer other than brain cancer or CNS lymphoma * Laboratory values obtained <= 30 days prior to registration: * Hgb >= 10 g/dL * Willing and able to provide informed consent * Negative pregnancy test (urine or serum) done <= 7 days prior to registration, for women of childbearing potential only * Ability to complete questionnaire(s) by themselves or with assistance * Biological therapy (i.e. immunotherapy, biotherapy), chemotherapy or radiation therapy will be allowed * Use of a stable dose of anti-depressants (except tricyclic anti-depressants) will be allowed * Erythropoietic agents to treat anemia, and steroids as a part of cancer treatment and for symptom management (except for fatigue) will be allowed Exclusion Criteria: * Hypersensitivity to methylphenidate * Any prior use of methylphenidate * Concomitant (<= 2 weeks) use of prescription stimulants (pemoline, modafinil, amphetamines); other medications, herbal products or dietary supplements for fatigue * Uncontrolled hypertension [defined as systolic blood pressure (BP) >= 160 mmHg and/or diastolic BP >= 100 mmHg on 2 separate visits <= 2 months prior to randomization]; or a resting heart rate > 100 * Moderate or severe pain as defined by an average daily score >= 4 on a pain analog scale (0 - 10) * Known brain metastasis or primary CNS malignancy * Clinically significant acute or chronic progressive or unstable neurologic (dementia, delirium, or seizure disorder), hepatic, renal, cardiovascular, thyroid, or respiratory disease that would limit participation in the study per MD discretion or judgment * Psychiatric disorder such as manic depression, anxiety disorder, bipolar disorder, obsessive compulsive disorder, or schizophrenia * Major surgery < 4 weeks prior to registration. (Note: Insertion of central venous catheter is not considered major surgery.) * Using a drug contraindicated when taken concurrently with methylphenidate: coumarin anticoagulants, anticonvulsants, tricyclic antidepressants, antipsychotics, monoamine oxidase inhibitors, clonidine, theophylline, and pseudoephedrine Note: use of Compazine prescribed as an antiemetic is permitted for use while participating in this study. * Additional medical conditions where use of methylphenidate is contraindicated: glaucoma, motor tics, family history or diagnosis of Tourette's syndrome, history of drug or alcohol abuse or intestinal obstruction. * Pregnant women or nursing women. Women of childbearing potential who are unwilling to employ adequate contraception. This study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown. * Untreated hypothyroidism (TSH >= 5)

Study Objectives The purpose of this trial is to determine if low-dose mifepristone benefits women with symptomatic fibroids. Conditions: Leiomyoma Intervention / Treatment: DRUG: Mifepristone, DRUG: Inert Capsule Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE3 Primary Purpose: TREATMENT Allocation: RANDOMIZED Interventional Model: PARALLEL Masking: TRIPLE

Inclusion Criteria: * Gender: Female * Age: 18 - premenopausal * Have at least moderate symptoms of menorrhagia or pelvic pain/pressure * Have a total uterine volume greater than or equal to 160 cc by ultrasound measurement and at least one fibroid that is => 2.5cm in size * Have a score of equal to or greater than 39 on the Uterine Fibroid Symptom and Quality of Life scale * Declined standard treatment options for symptomatic fibroids * Agree to use a double-barrier method (condoms, diaphragms) or other effective non-hormonal methods of contraception (abstinence, sterilization) throughout participation in the study to prevent pregnancy and to report any exposure to pregnancy to the research staff immediately * Willing and able to give informed consent * Willing and able to comply with study requirements Exclusion Criteria: * Current or planned pregnancy during the study period * Menopausal, as indicated by follicle stimulating hormone (FSH) level of the reference laboratory * Currently breast-feeding * Untreated abnormal pap smear * Presence of conditions other than fibroids contributing to pain and/or bleeding * Hemoglobin < 9.0 mg/dl * Presence of adnexal masses or tenderness indicating further evaluation or surgery * Grade III or IV hydronephrosis by ultrasound * Severe, active mental health disorder * Active substance abuse or dependence * Presence of any contraindication to mifepristone including: * Adrenal insufficiency by history * Sickle cell disease * Active liver disease (liver function tests greater than 1.5 times upper range of normal) * Severe, respiratory disease (P02 saturation< 92%) * Renal disease (serum creatinine > 1.5 mg/dl) * Blood clotting defect. (abnormal PT and PTT) * Thromboembolic disease (history of deep vein thrombosis or pulmonary embolus) * Current or recent (within the past 3 months) use of the following medications: * Oral or systemic corticosteroids * Hormones: estrogens, progestins, oral contraceptives * Danazol, anticoagulants * Herbal or botanical supplements with possible hormonal effects. * Use within the past six months of the gonadotropin releasing hormones (GnRH) analogs or Depo-Provera. * Current or planned use during the study of any of the following medications/or products: * ketoconazole, * itraconazole, * erythromycin, * grapefruit juice, * rifampin, * St John's Wort, * phenytoin, * phenobarbital, or * carbamazepine

Study Objectives Chemoradiotherapy has become the standard of care for women with locally advanced cervical cancer. The available data support a 30 to 50% reduction in the risk of death from cervical cancer for women with locally advanced disease undergoing radiotherapy (RT) and concomitant cisplatin-based chemotherapy compared to RT alone. Despite the fact that this is currently the best treatment of locally advanced cervical cancer, 5-year overall survival is still only 52%. The fully human, agonist monoclonal antibody mapatumumab binds to the Tumor necrosis factor-Related Apoptosis-Inducing Ligand Receptor 1 (TRAIL-R1, DR4) and induces cytotoxicity in multiple tumor cell lines in vitro and in vivo. In multiple phase I and phase II studies, mapatumumab appeared to be safe both as single agent and in combination with chemotherapy, including cisplatin. In cervical cancer cell lines, mapatumumab induced apoptosis in 51% of the cells. Mapatumumab in combination with irradiation increased apoptosis to 83%. In this phase 1b/2 study, the investigators will evaluate the safety, tolerability and efficacy of mapatumumab in combination with cisplatin and radiotherapy in patients with locally advanced cervical cancer. Conditions: Advanced Cervical Cancer Intervention / Treatment: DRUG: mapatumumab, DRUG: cisplatin, RADIATION: radiotherapy Location: Netherlands Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1, PHASE2 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Patients with histologically or cytologically confirmed stage IB2, IIA2, IIB, III, and IVA cervical cancer, according to the FIGO classification * Adequate bone marrow, renal and liver function: * Absolute neutrophil count >= 1.5 x 109 /L. * Platelet count >= 100 x 109 /L. * Serum creatinine level <= 1.5 x upper limit of normal (ULN). * Total bilirubin < 1.25 x ULN. * Aspartate transaminase (AST) and alanine transaminase (ALT) <= 2.5 x ULN. * Performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) Scale. * Age >= 18 years. * Life expectancy of >= 12 weeks. * Have the ability to understand the requirements of the study, provide written informed consent (including consent for the use and disclosure of research-related health information), and comply with the study and follow-up procedures. Exclusion Criteria: * Any co-morbid condition that in the judgment of the investigator renders the subject at high risk of treatment complications or reduces the possibility of assessing clinical effect. * Cytotoxic agent, hormonal therapy, or radiation therapy within 3 weeks (6 weeks for nitrosoureas or mitomycin-C) prior to day 1, cycle 1; investigational agent within 4 weeks prior to day 1, cycle 1. * Need for concomitant anticancer therapy (surgery, radiation therapy, chemotherapy, immunotherapy, radiofrequency ablation) or other investigational agents during the study treatment period. * Major surgery within 4 weeks before enrollment; minor surgery (except for insertion of vascular access device) within 2 weeks before enrollment; or not yet recovered from the effects of the surgery. * Systemic steroids within 1 week before enrollment except steroids used as part of an antiemetic regimen or maintenance-dose steroids for non-cancerous disease. * History of any infection requiring hospitalization or antibiotics within 2 weeks before enrollment. * Known brain or spinal cord metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids. * Known human immunodeficiency virus infection. * Unstable angina, myocardial infarction, cerebrovascular accident, > Class II congestive heart failure according to the New York Heart Association Classification for Congestive Heart Failure within 6 months before enrollment. * Pregnant female or nursing mother.

Study Objectives This non-interventional, multinational study of topical field treatment of actinic keratosis (AK) aims to collect real-life experience with ingenol mebutate as well as one or two other topical field therapies commonly used in the individual country. Physicians will report baseline characteristics, while the main study focus will be on patient reported outcomes 3-4 weeks after treatment completion (treatment satisfaction, adherence, resource utilization and Health Related Quality of Life. Dermatology centres in Denmark, Norway, Sweden, the Netherlands, the United Kingdom and Canada will participate. Conditions: Actinic Keratosis Intervention / Treatment: DRUG: Ingenol mebutate, DRUG: 5-fluorouracil, DRUG: Imiquimod, DRUG: Diclofenac Location: Netherlands Study Design and Phases Study Type: OBSERVATIONAL

Inclusion Criteria: Patients eligible to receive topical treatment with one of the following for treatment of actinic keratosis at the discretion of the dermatologist: Ingenol mebutate, 5-fluorouracil, imiquimod, diclofenac. Informed consent. * Exclusion Criteria: Any on-going treatments at study start with ingenol mebutate, 5-fluorouracil, imiquimod or diclofenac; other topical treatment for AK in treatment area; pregnancy or planned pregnancy within treatment period. *

Study Objectives The purpose of this study is to find a safe and tolerable dose of Lipotecan® when administered to patients with advanced solid tumors. Conditions: Advanced Solid Tumors Intervention / Treatment: DRUG: Lipotecan Location: United States, Taiwan Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE1 Primary Purpose: TREATMENT Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Adult patients defined by age >=18 years. * Pathologically confirmed advanced solid tumors for which standard therapy proven to provide clinical benefit does not exist or is no longer effective * Evaluable disease, either measurable on imaging or with informative tumor marker(s), by RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Exclusion Criteria: * Pregnancy or lactation. Women of childbearing potential must have a negative pregnancy test within 7 days prior to enrolment. Male and female patients of childbearing potential must agree to use appropriate birth control (barrier methods with spermicides, oral or parenteral contraceptives and/or intrauterine devices) during the entire duration of the study, or the patient must be surgically sterile (with documentation in the patient's medical records). * Previous malignancy, except for non-basal-cell carcinoma of skin or carcinoma-in-situ of the uterine cervix, unless the tumor was treated with curative intent more than 2 years prior to study entry. * Receipt of more than 3 prior regimens of chemotherapy. * Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to baseline. Receipt of radiotherapy to >25 % of bone marrow. Major surgery within 4 weeks prior to baseline. * Concomitant treatment with, or anticipated use of, pharmaceutical or herbal agents which are potent inhibitors or inducers of cytochrome P450 enzymes unless approved by the Sponsor. * Uncontrolled intercurrent illness that would jeopardize patient safety, interfere with the objectives of the protocol, or limit patient compliance with study requirements, as determined by the Investigator.

Study Objectives Gemcitabine is considered one of the standard drugs for advanced pancreatic cancer and is approved by the FDA to treat it. Cabozantinib is a new drug that has demonstrated effectiveness against pancreatic cancer in laboratory experiments, especially when given with gemcitabine. Initial studies with cabozantinib in pancreatic cancer have shown some activity against the disease. The purpose of this study is to determine the safest and highest dose of cabozantinib that can be given together with standard doses of gemcitabine in patients with pancreatic cancer. This study will determine the safety and tolerability of this two drug combination. Conditions: Pancreatic Cancer Intervention / Treatment: DRUG: CABOZANTINIB, DRUG: gemcitabine 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: * pathologically confirmed pancreatic carcinoma. * locally advanced unresectable disease, metastatic disease, or recurrent disease following surgical therapy. * >= 18 years old. * Life expectancy of greater than 12 weeks. * ECOG performance status <=1 (Karnofsky >=70%) (See Appendix A). * adequate organ and marrow function as follows: * capable of understanding and complying with the protocol requirements and has signed the informed consent document. * use medically accepted barrier methods of contraception * women of childbearing potential must have a negative pregnancy test at screening. Exclusion Criteria: * neuroendocrine tumors of the pancreas. * more than 1 prior systemic treatment regimen for pancreatic cancer. may have received prior neoadjuvant or adjuvant therapy, including gemcitabine, provided 6 months have elapsed from completion of that treatment and the start of study therapy. * Previous gemcitabine therapy for advanced pancreatic cancer. Patients who have had chemotherapy within 4 weeks, nitrosoureas/mitomycin C within 6 weeks, or monoclonal antibody within 6 weeks prior to planned initiation of study treatment. * prior treatment with a small molecule kinase inhibitor or a hormonal therapy within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment. * have received an investigational agent within 28 days of the first dose of study treatment or 5 half-lives of the compound or active metabolite, whichever is longer. * have received radiation therapy within 14 days of study treatment. * have not recovered from toxicity due to all prior therapies (i.e., return to pretherapy baseline or to CTCAE Grade 0 or 1) except alopecia and non-clinically significant AEs. * known brain metastases.

Study Objectives This is a pilot phase 2 single-arm study, of men with metastatic castration-resistant prostate cancer (mCRPC). Patients will be treated with any of the approved life-prolonging therapies: abiraterone 1000 mg daily plus prednisone 5 mg (or dexamethasone 0.5 mg) daily, enzalutamide 160 mg daily, or docetaxel 50 mg/m2 every two weeks or 75 mg/m2 every three weeks. Conditions: Metastatic Castration-resistant Prostate Cancer Intervention / Treatment: DRUG: 18F-fluciclovine PET Scan Location: United States Study Design and Phases Study Type: INTERVENTIONAL Phase: PHASE2 Primary Purpose: OTHER Allocation: NA Interventional Model: SINGLE_GROUP Masking: NONE

Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) Performance status 0-2; * Age >= 18 years; * Histologically confirmed adenocarcinoma of the prostate; * Ongoing use of luteinizing hormone-releasing hormone (LHRH) required in the absence of surgical castration and castrate concentration of testosterone (< 50 ng/dL); * Detectable PSA of at least 2 ng/dL; * Metastatic disease documented by CT or bone scan within 42 days of cycle 1 day 1; * Life expectancy of >= 6 months; * Must have disease progression despite a castrate concentration of testosterone of < 50 ng/dL based on: A. PSA progression defined as increase in PSA of at least 2 ng/dL and 25% from nadir values of prior therapy, determined by 2 separate measurement taken at least 1 week apart; And/or B. Radiographic disease progression based on response evaluation criteria in solid tumors (RECIST) 1.1 for soft tissue disease and/or prostate cancer working group 3 (PCWG3) for bone only disease; * No prior life-prolonging therapies for mCRPC are allowed, except Sipuleucel-T; * The use of docetaxel in the metastatic hormone-sensitive prostate cancer (mHSPC) setting is allowed; * Low dose prednisone (10 mg or less) or equivalent is allowed; * Acceptable liver function (within 28 days from enrollment) defined as: A. Bilirubin < 2.5 times upper limit of normal (ULN), except for patients with known Gilbert disease (in such cases bilirubin < 5 times ULN); B. AST (SGOT) and ALT (SGPT) < 3 times ULN * Acceptable renal function (within 28 days from enrollment): A. Serum creatinine <= 2.0 x ULN or creatinine clearance >= 30 mL/min * Acceptable hematologic status (within 28 days from enrollment): A. Absolute neutrophil count (ANC) >= 1000 cell/mm3 (100 x 109/L) B. Platelet count >= 100,000 platelet/mm3 (100 x 109/L) C. Hemoglobin >= 9 g/dL * At least 2 weeks since prior radiation before starting study treatment (cycle 1 day 1); * Able to understand and willing to sign a written informed consent document; * Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 1 week after last dose of abiraterone acetate. Exclusion Criteria: * Pathological findings consistent with small cell carcinoma of the prostate; * Prior treatment with docetaxel for metastatic castration-resistant prostate cancer (CRPC); * Patient with normal 18F-flucicolovine PET/CT scans at baseline; * Know allergies, hypersensitivity, or intolerance to abiraterone, prednisone, 18F-fluciclovine or their excipients; * Any chronic medical condition requiring >= 10 mg daily of systemic prednisone (or equivalent); * Major surgery (e.g., required general anesthesia) within 2 weeks before screening; * Uncontrolled active infection (including hepatitis B or C or AIDS). Patients with hepatitis B/C who have disease under control and no significant liver function impairment, and undetectable viral load will be allowed to participate. Similarly, patients with known HIV and >= 400 CD4 + T cells are allowed to participate; * Evidence of other metastatic malignancies within the last year; * Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study.

Study Objectives The main purpose of this study is to characterize the distribution, metabolism, and elimination (ADME) of Patupilone after a single intravenous administration in patients with advanced solid tumor malignancies Conditions: Advanced Malignancies, Solid Tumors Intervention / Treatment: DRUG: Patupilone 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 years * World Health Organization (WHO) Performance Status Score of: 0- you are fully active and more or less as you were before your illness, 1 - you cannot carry out heavy physical work, but can do anything else. * Adequate hematological laboratory parameters * No major impairment of renal or hepatic function * Female patients must have a negative serum pregnancy test at screening. Exclusion Criteria: * Severe and/or uncontrolled medical disease; * Severe cardiac insufficiency with uncontrolled and/or unstable cardiac or coronary artery disease; * Known diagnosis of human immunodeficiency virus (HIV) infection; * Presence of any other active or suspected acute or chronic uncontrolled infection; * Symptomatic brain metastases or leptomeningeal disease. Other protocol-defined inclusion/exclusion criteria may apply.