DISEASE CHARACTERISTICS:

Inclusion criteria:

• Diagnosis of unresectable metastatic or locally advanced, low- or intermediate-grade neuroendocrine carcinoma, including the following subtypes:

  • Carcinoid tumor, low-grade or well differentiated neuroendocrine carcinoma
  • Atypical carcinoid tumor, intermediate-grade or moderately differentiated neuroendocrine carcinoma

• High-risk disease as defined by at least one of the following:

  • Progressive disease
  • Refractory carcinoid syndrome while receiving octreotide acetate (i.e., defined by > 2 flushing episodes/day or > 4 bowel movements/day)
  • Atypical histology and more than 6 lesions

  • Metastatic colorectal carcinoid tumor

    • Patients with metastatic cecal or appendiceal carcinoid tumor are not eligible unless they fit other mentioned high-risk features
  • Metastatic gastric carcinoid tumor
• Measurable disease
• Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid tumor, or goblet cell carcinoid tumor are not eligible

Exclusion criteria:

• Osseous metastasis as only site of disease
• Medullary thyroid carcinoma or islet cell carcinoma
• History of primary brain tumor or metastatic cancer to the brain

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Zubrod performance status 0-2
• Platelet count > 100,000/mm³
• ANC > 1,500/mm³
• Hemoglobin > 8 g/dL
• Serum bilirubin < 1.5 times upper limit of normal (ULN)
• SGOT and SGPT ≤ 2.5 times ULN
• Serum creatinine < 1.5 mg/dL
• 24-hour urine protein < 1,000 mg if urine protein:creatinine ratio > 0.5
• PT and PTT ≤ 1.1 times ULN
• History of hypertension must be well controlled (i.e., blood pressure < 150/90 mm Hg) on a stable regimen of antihypertensive therapy
• Not pregnant or nursing
• Fertile patients must use effective barrier method contraception during and for 6 months after completion of study treatment

Exclusion criteria:

• History or evidence of clinically significant peripheral vascular disease (e.g., non-healing peripheral ulcers or claudication)
• Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
• Bleeding diathesis or coagulopathy that results in spontaneous bleeding (in the absence of trauma) requiring red blood cell transfusion within the past 5 years
• Serious (i.e., requiring active medical therapy with medication or medical device under the supervision of a physician) non-healing wound, ulcer, or bone fracture

• Recent history (i.e., within the past 6 months) of any of the following arterial thromboembolic events:

  • Transient ischemic attack
  • Cerebrovascular accident
  • Unstable angina
  • Myocardial infarction
  • New York Heart Association class II or higher congestive heart failure
• Hemoglobinopathies (e.g., Thalassemia) or any other cause of hemolytic anemia
• Pregnant or nursing
• Any other prior malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer

• Any immunologically mediated disease, including any of the following:

  • Inflammatory bowel disease (Crohn disease, ulcerative colitis)
  • Rheumatoid arthritis
  • Idiopathic thrombocytopenia purpura
  • Systemic lupus erythematosus
  • Autoimmune hemolytic anemia
  • Scleroderma
  • Severe psoriasis
• Any serious intercurrent infections or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this treatment
• Psychiatric disorders rendering patient incapable of complying with the requirements of the protocol

PRIOR CONCURRENT THERAPY:

• Recovered from all prior therapy
• At least 28 days since and no more than 1 prior regimen of cytotoxic chemotherapy

• At least 28 days since prior hepatic artery embolization provided there is residual measurable disease

  • Chemoembolization is considered as 1 prior chemotherapy regimen
• No prior interferon, bevacizumab, or any other therapy targeting VEGF or VEGF receptors (e.g., SU11248, PTK/ZK, sorafenib tosylate, or pazopanib hydrochloride)
• Prior therapy targeting c-kit, abl, PDGFR, mTOR, and somatostatin receptors allowed

• At least 28 days since prior radiotherapy

  • Target lesions must have show disease progression if therapy included peptide receptor radiotherapy
• At least 1 week since prior minor surgery
• At least 4 weeks since prior major surgery
• At least 21 days since prior octreotide acetate therapy

• Concurrent full-dose anticoagulation (warfarin or low molecular weight heparin) allowed provided the following criteria are met:

  • In-range INR (e.g., between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
  • No active bleeding or pathological condition that carries a high risk of bleeding (e.g., varices)

• No concurrent interferon to control carcinoid syndrome for patients receiving bevacizumab

  • Other supportive care medication (e.g., short acting octreotide acetate) allowed
• No other concurrent chemotherapy, immunotherapy, radiotherapy, hepatic artery embolization, hepatic artery chemoembolization, radiofrequency ablation, or other tumor ablative procedure
• No other investigational or commercial agents