Patient must have unresectable metastatic or locally advanced, low- or intermediategrade neuroendocrine carcinoma.

**check 19.6/ 3.0 for test schedule timing step 2 randomization

Patient 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. Patients with metastatic cecal
or appendiceal carcinoid tumor are not eligible unless the tumors fit
into one of the other highriskcategories (a, b, or c above).
e. Metastatic gastric carcinoid

Patient must have measurable disease

Patient may have had up to one prior regimen of cytotoxic chemotherapy. At least 28 days must have elapsed since completion of prior therapy, and patient must have recovered from all effects.

Patient may have had prior hepatic artery embolization. At least 28 days must have elapsed since embolization and there must be residual measurable disease.
Chemoembolization will be considered as one prior chemotherapy regimen.

Patient must not have received prior interferon, bevacizumab or any other therapy targeting VEGF or VEGF receptors (i.e., SU11248, PTK/ZK, BAY 43-9006, GW786034).

Patient may have received prior therapy targeting c-kit, abl, PDGFR, mTOR, and
somatostatin receptors (not counted toward prior cytotoxic chemotherapy).

Prior radiation is allowed. There must be measurable disease. If prior therapies include peptide receptor radiotherapy, the target lesion(s) must have shown disease progression. At least 28 days must have elapsed since completion of prior therapy, and patient must have recovered from all effects.

At least 21 days must have elapsed since any prior octreotide treatment.

Patient must not have a history of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 28 days prior to registration.

Patient must not have history within the past 5 years or presence of bleeding diathesis or coagulopathy that results in spontaneous bleeding (in the absence of trauma) requiring pRBC transfusion.

Patient must not have recent history (within 6 months prior to registration) of these arterial thromboembolic events: transient ischemic attack, cerebrovascular accident, unstable angina, myocardial infarction, or New York Heart Association Grade II or higher congestive heart failure.

Patient must not have hemoglobinopathies (e.g., Thalassemia) or any other cause of hemolytic anemia.