Phase III Prospective Randomized Comparison of Depot Octreotide plus Interferon Alpha versus Depot Octreotide plus Bevacizumab (NSC #704865) in Advanced, Poor Prognosis Carcinoid Patients

Unresectable metastatic or locally advanced, low- or intermediate-grade neuroendocrine carcinoma. Must have high-risk disease as defined by at least one of the following: (a) progressive disease; (b) refractory carcinoid syndrome while receiving octreotide (defined by > 2 flushing episodes/day or > 4 bowel movements/day); (c) atypical histology and more than 6 lesions; (d) metastatic colorectal carcinoid; (e) metastatic gastric carcinoid. Patients with metastatic cecal or appendiceal carcinoid tumors are not eligible unless the tumors fit into one of the other high-risk categories (a, b, or c above). Measurable disease. CT or MRI for tumor measurement within 28 days prior to reg. Assessment of non-measurable disease within 42 days prior to reg. Scans must be submitted for central review. Must seek additional consent for submission of octreotide scans, submission of blood, and use of archived tissue for correlative studies. May have had up to one prior regimen of cytotoxic chemo. At least 28 days must have elapsed since its completion. May have had hepatic artery embolization. At least 28 days must have elapsed and there must be residual measurable disease. No prior interferon, bevacizumab or other therapy targeting VEGF or VEGF receptors. May have received prior therapy targeting c-kit, abl, PDGFR, mTOR, or somatostatin receptors. Prior RT allowed. At least 28 days must have elapsed since its completion. Must have recovered from any prior surgery. One week must have elapsed from the time of a minor surgery and 4 weeks from major surgery. At least 21 days must have elapsed since any prior octreotide treatment. Zubrod 0-2. Within 28 days prior to reg: ANC > 1,500/mcl; hemoglobin > 8 g/dl; platelets > 100,000/mcl; serum bilirubin < 1.5 x IULN; SGOT/SGPT </= 2.5 x IULN; serum creatinine < 1.5 mg/dL; UPC ratio; PT and PTT </= 1.1 x IULN. No history of clinically significant peripheral vascular disease. No history of primary brain tumor or metastatic cancer to brain. No history of abdominal fistula, GI perforation, or intra-abdominal abscess within 28 days prior to reg. No history within past 5 years or presence of bleeding diathesis or coagulopathy that results in spontaneous bleeding requiring pRBC transfusion. No serious non-healing wound, ulcer, or bone fracture. No history within past 6 months of: transient ischemic attack; cerebrovascular accident; unstable angina, myocardial infarction; New York Heart Association Grade II or higher congestive heart failure. Pts with history of hypertension must be well-controlled on stable regimen of antihypertensives. Must not have hemoglobinopathies or any other cause of hemolytic anemia. Must not plan to use any other concurrent treatment while on protocol treatment. Must not be pregnant or nursing. No other prior malignancy except adequately treated basal or squamous cell skin cancer, other adequately treated in situ cancer, or any other cancer from which the pt has been disease free for five years.