Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Discontinuation Study of Brivanib Alaninate (BMS-582664) Versus Placebo in Subjects With Advanced Tumors
Brief Summary: The purpose of this study is to determine if gastric/esophageal, lung, pancreatic, bladder and sarcoma patients show benefit from brivanib treatment. Patients who clearly do, stay on treatment. Those in which it is unclear will be randomized to continue or withdraw treatment to determine whether that benefit is related to brivanib


Options:
A: Inclusion Criteria:

* Female subjects, ≥18 years, histologically proven recurrent advanced epithelial ovarian, fallopian tube or primary peritoneal carcinomas
* Have either undergone a hysterectomy or bilateral oophorectomy/salpingectomy and/or have been postmenopausal for 24 consecutive months (i.e. who have not had menses at any time in the preceding 24 consecutive months without an alternative medical cause)
* Performance status 0-2
* Adequate organ function
* Life expectancy \>6 weeks
* Has received 2 or more lines of chemotherapy for ovarian cancer and patient is platinum resistant or platinum intolerant or not suitable for any further standard intravenous chemotherapy
* No previous oral cyclophosphamide, nintedanib, or other tyrosine kinase inhibitors such as cediranib but patients can have received anti-VEGF therapies such as bevacizumab as they will be stratified for this
* Measurable lesions according to RECIST 1.1 criteria or serum CA125 levels for evaluation by GCIG CA125 criteria are welcomed but not a prerequisite for inclusion as response will only be assessed for those with evaluable disease
* Able to give written informed consent and to complete QoL

Exclusion Criteria

* Carcinosarcoma or malignant tumour of non-epithelial origin (e.g. germ cell tumour, sex cord-stromal tumour) of the ovary, fallopian tube or peritoneum
* Clinically relevant non-healing wound, ulcer (intestinal tract, skin) or bone fracture
* Symptoms or signs of gastrointestinal obstruction requiring parenteral nutrition or hydration or any other GI disorders or abnormalities that would interfere with drug absorption or inability to take oral medication
* Active brain metastases (i.e. symptoms deteriorating, changing condition in \< 4 weeks) or leptomeningeal disease. Trial entry is allowed if the brain metastases are stable (asymptomatic or condition stable for \> 4 weeks).
* Dexamethasone for brain metastases is allowed if administered as stable dose for \> 4 weeks before randomisation (if \< 4 weeks then the patient is not eligible)
* Clinically relevant therapy-related toxicity from previous chemotherapy and radiotherapy
* History of major thromboembolic event within the last 6 months, such as pulmonary embolism or proximal deep vein thrombosis, unless on stable therapeutic anticoagulation (\>3 months if on warfarin, PT / INR needs to be monitored regularly as per table 8.1 in protocol)
* Known inherited or acquired bleeding disorder
* Significant cardiovascular diseases, including uncontrolled hypertension, clinically relevant cardiac arrhythmia, unstable angina or myocardial infarction within the past 6 months, congestive heart failure \> NYHA II, severe peripheral vascular disease, significantly relevant pericardial effusion
* History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 6 months
* Radiographic evidence of cavitating or necrotic tumours with invasion of adjacent major blood vessels
* Laboratory values indicating an increased risk for adverse events:

  1. calculated GFR \< 45 ml/min. Sites can use any calculation method according to local practice.
  2. absolute neutrophil count (ANC) \< 1.5x109/L
  3. platelets \< 100 x109/L
  4. haemoglobin \< 90 g/L
  5. proteinuria CTCAE 2 or greater
  6. total bilirubin \> x 2 ULN
  7. ALT and/or AST \> 1.5 x ULN
  8. unless liver metastases present when ALT or AST \> 2.5 ULN
  9. International normalized ratio (INR) \> 2 or activated partial thromboplastin time (APTT) \>1.5 x ULN in the absence of therapeutic anticoagulation. INR \> 4 or APTT \> 2.5 x ULN in presence of therapeutic anticoagulation
* Serious infections in particular if requiring systemic antibiotic (antimicrobial, antifungal or antiviral therapy), including hepatitis B and/or C infection, HIV- infection
* Poorly controlled diabetes mellitus or patient on sulphonylurea-type hypoglycaemics (e.g. gliclazide) as main diabetic control (as contraindicated with cyclophosphamide)
* Previous breast cancer patients are permitted only if diagnosis and any chemotherapy treatment for this was \> 5 years previously and there is no evidence of metastatic breast cancer at trial entry (Please contact UCL CTC / CI if patient still on hormone treatment for breast cancer).
* Other malignancy diagnosed within the past 5 years. In exception to this rule, the following malignancies may be included:

  1. non-melanoma skin cancer (if adequately treated)
  2. cervical carcinoma in situ (if adequately treated)
  3. prior or synchronous endometrial cancer (if adequately treated), provided all of the following criteria are met: G1 or G2, no LVSI and FIGO (2010) stage IA only
* Serious illness or concomitant non-oncological disease such as neurologic, psychiatric or infectious disease or a laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study
* Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule e.g. active alcohol or drug abuse
* Any contraindications for therapy with cyclophosphamide, e.g. a history of severe hypersensitivity reactions to listed excipients for cyclophosphamide treatment with other investigational drugs
* Patients should not commence trial treatment within 6 weeks of any major surgical procedure
* Participation in another clinical trial testing a drug within the past four weeks before start of therapy or concomitantly with this trial
* Chemotherapy, including immunotherapy or monoclonal antibody treatment (VEGF) within 4 weeks of starting study treatment
* Hormone treatment for ovarian cancer within 2 weeks of starting study treatment (ongoing HRT is allowable)
* Any previous tyrosine kinase inhibitor treatment that has predominantly anti-angiogenic action
* Radiotherapy within 3 months not allowed except when given for symptom control \>28d previously. All patients receiving any radiotherapy will require evidence of recurrent ovarian cancer outside the irradiated field either on imaging or via rising CA125
* Hypersensitivity to nintedanib, peanut or soya, or to any of the excipients of nintedanib
B: For additional information, please contact the BMS oncology clinical trial information service at 855-216-0126 or email MyCancerStudyConnect@emergingmed.com. Please visit www.BMSStudyConnect.com for more information on clinical trial participation.

Inclusion Criteria:

* Life expectancy at least 3 months
* Diagnosis of a solid tumor which is unresectable in which no approved effective therapy exists or for subjects who are intolerable to such therapy. The initial enrollment will focus on non-small cell lung, gastric/esophageal adenocarcinoma, soft tissue sarcoma, transitional cell carcinoma, and pancreatic cancer including ampulla of Vater tumors
* Adequate tumor sample
* Adequate recovery (baseline or Grade 1) from recent therapy. At least 1 week must have elapsed from the time of a minor surgery, and at least 8 weeks for major surgery or radiation therapy

Exclusion Criteria:

* Subjects with known brain metastasis.
* Subjects with signs or symptoms suggestive of brain metastasis are not eligible unless brain metastases are ruled out by CT or MRI

Medical History and Concurrent Diseases:

* History of thrombo-embolic disease within the last six months requiring therapeutic anticoagulation
* Subjects with history of poor wound healing or non healing ulcers
* Uncontrolled or significant cardiovascular disease

Allergies and Adverse Drug Reactions:

* History of allergy to brivanib its drug class, or related compounds

Prohibited Treatments and/or Therapies:

* Exposure to any investigational drug within 4 weeks of enrollment
* Other concurrent chemotherapy, hormonal therapy, immunotherapy regimens or radiotherapy, standard or investigational. Subjects may continue to receive hormone replacement therapy
* Prior exposure to brivanib
C: Participants who met the following criteria were eligible for the study.

Inclusion Criteria:

* Histologically-confirmed ovarian epithelial (including fallopian tube and primary peritoneal) adenocarcinoma.
* Prior treatment with at least 2 treatment regimens in the advanced disease treatment setting
* Platinum-resistant disease defined by relapse or progression of disease during or after treatment, or drug intolerance
* Topotecan- and/or liposomal doxorubicin-resistant disease defined by relapse or progression of disease during or after treatment, or drug intolerance
* Evidence of at least one unidimensional measurable tumor lesion by computed tomography (CT) or magnetic resonance imaging (MRI) scan according to Response Evaluation Criteria in Solid Tumors (RECIST) that has not been treated with surgery or radiation therapy

Exclusion Criteria:

* Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or for in situ carcinoma of the cervix uteri
* Prior treatment with a vascular endothelial growth factor (VEGF) or VEGF receptor inhibitor
* More than 3 chemotherapy regimens in the advanced disease treatment setting
* Uncontrolled hypertension

The above information is not intended to contain all considerations relevant to potential participation in a clinical trial.
D: Inclusion Criteria:

1. Patients with histologically confirmed epithelial ovarian cancer, primary peritoneal carcinomatosis or fallopian tube cancer
2. Patients must have platinum resistant (relapse-free interval \< 6 months of a platinum-containing primary or secondary therapy) or platinum refractory (progression during primary or secondary platinum treatment) disease defined by measurable disease according to RECIST or elevated CA-125 level according the GCIG-criteria.

   Definition of relapse: Demonstration of measurable or non-measurable tumour according to RECIST criteria by an imaging procedure (where applicable before relapse surgery) or increase in the tumour marker CA-125 to twice the upper laboratory value of normal for the hospital or histological confirmation of tumour relapse by biopsy or surgery.
3. No more than 2 prior treatment regimens for recurrent epithelial ovarian cancer.
4. Elevated CA-125-value before study entry in order to assess the response according the GCIG-criteria (see below). Patients without elevated CA-125 may be enrolled if they show a measurable or not-measurable disease (according RECIST) evaluated by imaging techniques (measurable disease - at least one unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan) or histologically or cytologically confirmed relapse
5. ECOG Performance Status of 0 or 1
6. ≥ 18 years age
7. The patient must be recovered from a prior operation. The operation must be performed at least 4 weeks prior to start of study drug,
8. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening

   * Hemoglobin ≥ 9.0 g/dl
   * Leucocyte count ≥ 3.000/micro liter
   * Absolute neutrophil count (ANC) major than 1.500/micro liter
   * Platelet count ≥ 100.000/micro liter
   * PT-INR/PTT \< 1.5 x upper limit of normal \[Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists\].
   * Total bilirubin \< 1,0 times the upper limit of normal
   * ALT and AST \< 2,5 x upper limit of normal (\< 5 x upper limit of normal for patients with liver involvement of their cancer); Alkaline phosphatase \< 4 x ULN
   * Calculated creatinine clearance ≥ 50 ml/min or serum creatinine ≤ 1,2 x upper limit of institutional values (according to Cockcroft and Gault)
9. Life expectancy of at least 12 weeks
10. Signed and dated written informed consent before the start of specific protocol procedures.

Exclusion Criteria:

1. History of cardiac disease: congestive heart failure \>NYHA class 2; active coronary artery disease (CAD) or myocardial infarction within the past 6 months (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled arterial hypertension with systolic blood pressure \>160 mmHg or diastolic blood pressure \> 90 mm Hg despite optimal treatment
2. Previous or concurrent cancer that 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 \> 5 years prior to study entry
3. Prior radiological or clinical evidence of CNS metastases including previously treated, resected, or asymptomatic brain lesions or leptomeningeal involvement by head CT scan or MRI
4. Known or suspected hypersensitivity reaction to topotecan or any ingredient of topotecan or sorafenib or any ingredient of sorafenib
5. Active clinically serious infections (\> grade 2 NCI-CTC version 3.0)
6. History of HIV infection or chronic hepatitis B or C
7. History of organ allograft
8. Patients with history of colon perforation
9. Patients with history of colitis or neutropenia colitis
10. Patients with evidence or history of bleeding diathesis
11. Serious non healing wound, fracture or ulcer
12. Patients undergoing renal dialysis
13. Patients unable to swallow oral medications
14. Significant disease which, in the investigator's opinion, would exclude the patient from the study
15. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
16. Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
17. Medical or psychological conditions that would not permit the subject to complete the study or sign informed consent
18. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
19. Legal incapacity or limited legal capacity
20. Participation in another clinical study with experimental therapy within the 30 days before start of treatment
21. Subjects housed in an institution on official or legal orders.

    Excluded therapies and medications, previous and concomitant:
22. Patients with prior therapy containing topotecan
23. Patients with prior therapy containing Avastin or other VEGFR TK1
24. Any other anticancer chemotherapy or immunotherapy or investigational drug therapy outside of this trial during the study or within 4 weeks prior to study entry.
25. Radiotherapy during study or within 4 weeks prior to start of study drug and prior radiotherapy of \> 25% of the bone marrow (exception: palliative radiotherapy of non-target lesions or pain therapy or local bone irradiation)
26. Autologous bone marrow transplant or stem cell rescue within 4 months of study

Answer: B