Octreotide Acetate and Recombinant Interferon Alfa-2b or Bevacizumab in Treating Patients With Metastatic or Locally Advanced, High-Risk Neuroendocrine Tumor

Inclusion Criteria:

   - Patient must have unresectable metastatic or locally advanced, low- or
   intermediate-grade neuroendocrine carcinoma

      - NOTE: pathology report must state one of the following: carcinoid, low-grade or
      well-differentiated neuroendocrine carcinoma, atypical carcinoid,
      intermediate-grade or moderately differentiated neuroendocrine carcinoma;
      patients with poorly differentiated neuroendocrine carcinoma, high-grade
      neuroendocrine carcinoma, adenocarcinoid, or goblet cell carcinoid are not
      eligible; patient must not have osseous metastasis as only site of disease;
      patients with medullary thyroid carcinoma or islet cell carcinoma are not
      eligible; if pathology report states only neuroendocrine carcinoma, pathology
      subtype must be reconfirmed

      - Occasionally, it is not possible to establish tumor grade on fine-needle
      aspiration (FNA) cytology material; if a new biopsy is needed, a core needle
      biopsy should be obtained whenever possible

   - Patient must have high risk disease as defined by at least one of the following:

      - Progressive disease

      - Refractory carcinoid syndrome while receiving octreotide (defined by > 2 flushing
      episodes/day or > 4 bowel movements/day)

      - Atypical histology and more than 6 lesions

      - Metastatic colorectal carcinoid; patients with metastatic cecal or appendiceal
      carcinoid tumor are not eligible unless the tumors fit into one of the other
      high-risk categories (a, b, or c above)

      - Metastatic gastric carcinoid

   - Patient must have measurable disease; CT or magnetic resonance imaging (MRI) used for
   tumor measurement must have been completed within 28 days prior to registration;
   X-rays, scans or other tests for assessment of non-measurable disease must have been
   performed within 42 days prior to registration; all disease must be assessed and
   documented on the Baseline Tumor Assessment Form; these scans also must be submitted
   for central radiology review

   - Institutions are required to submit CT/MRI scans and archived tissue for pathology
   review; furthermore, institutions are required to seek additional patient consent for
   submission of octreotide scans, and submission of blood and use of archived tissue for
   correlative studies

   - If patient consents to the submission of octreotide scans, the patient must also be
   registered to Registration Step 2

   - 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

   - Patient may have received prior therapy targeting stem cell factor receptor (c-kit),
   abelson murine leukemia viral oncogene homolog 1 (abl), platelet-derived growth factor
   receptor (PDGFR), mammalian target of rapamycin (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

   - Patients 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 LAR depot treatment

   - Patient must have a Zubrod performance status of 0-2

   - Absolute neutrophil count (ANC) > 1,500/mcl

   - Hemoglobin > 8 g/dl

   - Platelets > 100,000/mcl

   - Serum bilirubin < 1.5 x institutional upper limit of normal (IULN)

   - Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate
   transaminase (SGPT) =< 2.5 x IULN

   - Serum creatinine < 1.5 mg/dL

   - Urine protein must be screened by urine analysis for Urine Protein Creatinine (UPC)
   ratio; for UPC ratio > 0.5, 24-hour urine protein must be obtained and the level must
   be < 1,000 mg for patient enrollment; these results must be obtained within 28 days
   prior to registration

      - Note: UPC ratio of spot urine is an estimation of the 24-hour urine protein
      excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of
      1 gm

   - Patients not on anticoagulation must have prothrombin time (PT) and partial
   thromboplastin time (PTT) =< 1.1 x lULN obtained within 28 days prior to registration;
   patients on full-dose anticoagulation (warfarin or low molecular weight heparin) are
   eligible provided that both of the following criteria are met:

      - The patient has an in-range international normalized ratio (INR) (usually between
      2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low
      molecular weight heparin

      - The patient has no active bleeding or pathological condition that carries a high
      risk of bleeding such as varices

   - Patient must not have history or evidence of clinically significant peripheral
   vascular disease such as non-healing peripheral ulcers or claudication

   - Patient must not have a history of primary brain tumor or metastatic cancer to the
   brain; brain imaging studies are not required for eligibility if the patient has no
   neurological signs or symptoms; if brain imaging studies are performed, they must be
   negative for disease

   - Patient must not have a history of abdominal fistula, gastrointestinal perforation, or
   intra-abdominal 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 packed red blood cells (pRBC) transfusion

   - Patient must not have a serious (requiring active medical therapy with medication or
   medical device under the supervision of a physician) non-healing wound, ulcer, or bone
   fracture

   - 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

   - Patients with a history of hypertension must be well-controlled (blood pressure <
   150/90), on a stable regimen of antihypertensive therapy

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

   - Patient must not plan to use any other concurrent chemotherapy, immunotherapy, hepatic
   artery embolization, hepatic artery chemoembolization, radiofrequency ablation, other
   tumor ablative procedure or radiotherapy while on protocol treatment

   - Patient must not be pregnant or nursing because bevacizumab may be harmful to the
   developing fetus and newborn; male and female patients of reproductive potential must
   agree to employ an effective barrier method of birth control throughout protocol
   treatment and for up to 6 months following discontinuation of bevacizumab

   - No other prior malignancy is allowed except for the following: adequately treated
   basal cell or squamous cell skin cancer, or other adequately treated in situ cancer,
   or any other cancer from which the patient has been disease free for five years

   - All patients must be informed of the investigational nature of this study and must
   sign and give written informed consent in accordance with institutional and federal
   guidelines

   - At the time of patient registration, the treating institution's name and
   identification (ID) number must be provided to the Data Operations Center in Seattle
   in order to ensure that the current (within 365 days) date of institutional re view
   board approval for this study has been entered into the data base

   - REGISTRATION STEP 2 - SPECT SUBSTUDY

   - Patient must have registered to the main study

   - Patient must have consented to the submission of octreotide scans

   - An octreotide scan obtained within 28 days prior to Registration Step 1 must be
   available for submission