Ziv-Aflibercept in Treating and Computed Tomography Perfusion Imaging in Predicting Response in Patients With Pancreatic Neuroendocrine Tumors That Are Metastatic or Cannot Be Removed by Surgery

Less than 28 days elapsed from prior radiotherapy, from prior surgery and prior chemotherapy to the time of randomization; less than 42 days elapsed from prior major surgery to the time of randomization

Eastern Cooperative Oncology Group (ECOG) performance status (PS) \> 2

History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease

Other prior malignancy; adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix or any other cancer from which the patient has been disease free for \> 5 years are allowed

Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to study entry

Any of the following within 6 months prior to study entry: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure, stroke or transient ischemic attack

Any of the following within 3 months prior to study entry: grade 3-4 gastrointestinal bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event

Occurrence of deep vein thrombosis within 4 weeks, prior to study entry

Acquired immuno deficiency syndrome (AIDS-related illnesses) or known human immunodeficiency virus (HIV) disease requiring antiretroviral treatment

Any severe acute or chronic medical condition, which could impair the ability of the patient to participate to the study or to interfere with interpretation of study results

Pregnant or breast feeding women; positive pregnancy test (serum or urine beta-human chorionic gonadotropin \[HCG\]) for women of reproductive potential

Patient with reproductive potential (female and male) who do not agree to use an accepted effective method of contraception (hormonal or barrier methods, abstinence) during the study treatment period and for at least 3 months following completion of study treatment; for female patient enrolled, the following methods of contraception are acceptable: oral contraceptives accompanied by the use of a second method of contraception, or intra uterine device (IUD) or women who are surgically sterile, or women who are post -menopausal or other reasons have no chance of becoming pregnant

Absence of signed and dated Institutional Review Board-approved patient informed consent from prior to enrollment in the study

Urine protein-creatinine ratio (UPCR) \> 1 urinalysis or total urine protein \> 500 mg/24 hours (h)

Serum creatinine \> 1.5 x upper limit of normal (ULN); if creatinine 1.0-1.5 x ULN, creatinine clearance, calculated according to Cockcroft-Gault formula, \< 60 ml/min will exclude the patient

History of uncontrolled hypertension, defined as systolic blood pressure \> 150 mmHg while simultaneous diastolic blood pressure \> 100 mmHg, or systolic blood pressure \> 180 mmHg when diastolic blood pressure \< 90 mmHg, on at least 2 repeated determinations on separate days within 3 months prior to study enrollment

Patients on anticoagulant therapy with unstable dose of warfarin and/or having an out-of- therapeutic range INR (\> 3) within the 4 weeks prior to study entry

Evidence of clinically significant bleeding diathesis or underlying coagulopathy (e.g. INR \> 1.5 without vitamin K antagonist therapy), non-healing wound

What this study is about