Everolimus and Octreotide Acetate With or Without Bevacizumab in Treating Patients With Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors That Cannot Be Removed by Surgery

Inclusion Criteria:

   - Patients must have histologic documentation of well-differentiated or moderately
   differentiated neuroendocrine tumor from either a primary or metastatic site

      - If different histologic classification schemes are used, equivalent histologic
      classifications (for example "grade 1", "low-grade", or "intermediate-grade") are
      allowed

      - Patients with poorly differentiated neuroendocrine carcinoma or small cell
      carcinoma are excluded

      - Documentation from a metastatic disease site is sufficient if there is clinical
      evidence of a pancreatic primary site

   - Locally unresectable or metastatic disease

   - Patients must have either histologic documentation of a pancreatic primary site, or
   clinical evidence of a pancreatic neuroendocrine primary tumor as determined by the
   treating physician

      - Patients with neuroendocrine tumors (e.g., gastrinoma, VIPoma) in whom a
      pancreatic or peripancreatic primary site is strongly suspected are also eligible

   - Patients must have evidence of disease (measurable or non-measurable) with evidence of
   progression within the past 12 months

   - Measurable disease:

Lesions that can be accurately measured in at least one dimension (longest diameter to be
recorded) as >= 2 cm with conventional techniques or as >= 1 cm with spiral computed
tomography (CT) scan

   - Non-measurable disease:

All other lesions, including small lesions (longest diameter < 20 mm with conventional
techniques or < 10 mm with spiral CT scan) and truly non-measurable lesions; lesions that
are considered non-measurable include the following:

   - Bone lesions

   - Leptomeningeal disease

   - Ascites

   - Pleural/pericardial effusion

   - Inflammatory breast disease

   - Lymphangitis cutis/pulmonis

   - Abdominal masses that are not confirmed and followed by imaging techniques

   - Cystic lesions

      - No prior treatment with bevacizumab, everolimus, or other mammalian target of
      rapamycin (mTOR) inhibitors

      - Other prior treatments, including but not limited to prior cytotoxic
      chemotherapy, alpha interferon, tyrosine kinase inhibitors, external beam
      radiation therapy, and radiopeptide therapy are allowed

   - There is no limit on the number of prior treatment regimens

   - Any prior treatment (with the exception of octreotide) must be completed at least 4
   weeks prior to initiation of treatment

      - Prior treatment with embolization or ablative therapies is allowed if measurable
      disease remains outside of the treated area

   - There is no limit on the prior number of procedures

      - Treatment with somatostatin analogs is a requirement of the study

   - Patients receiving octreotide at the time of study entry may continue at the same dose
   level for the duration of the study

   - Patients not receiving octreotide will initiate treatment according to study
   guidelines

   - Prior progression on somatostatin analogs or a negative octreotide scan does not
   exclude patient participation in this study

      - Patients should have completed any major surgery >= 4 weeks from start of
      treatment

   - Patients must have completed any minor surgery >= 2 weeks prior to start of treatment

   - Patients must have fully recovered from the procedure

   - Insertion of a vascular access device is not considered major or minor surgery

      - Patients should not receive immunization with attenuated live vaccines within one
      week prior to registration or during protocol therapy

      - No concurrent condition resulting in immune compromise, including chronic
      treatment with corticosteroids or other immuno suppressive agents

      - No active or severe liver disease (e.g., acute or chronic hepatitis, cirrhosis);
      no positive anti-hepatitis B virus (HBV); HBV seropositive patients (hepatitis B
      surface antigen [HBsAg] positive) are eligible if they are closely monitored for
      evidence of active HBV infection by HBV deoxyribonucleic acid (DNA) testing, and
      they agree to receive suppressive therapy with lamivudine or other
      HBV-suppressive therapy until at least 4 weeks after the last dose of everolimus;
      patients who are hepatitis C antibody positive are eligible provided that
      hepatitis C viral load (hepatitis C ribonucleic acid [RNA]) is undetectable

      - No clinical evidence of brain metastases or carcinomatous meningitis

      - No history of gastrointestinal (GI) perforation within 12 months prior to
      registration

      - No history of clinically significant bleeding episodes

      - Patients on therapeutic anticoagulation are eligible for the study provided that
      they are on a stable dose of anticoagulants

      - No uncontrolled diabetes mellitus

      - Patients with a history of severely impaired lung function as defined as
      spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) that is
      50% of the normal predicted value and/or oxygen (O2) saturation that is 88% or
      less at rest on room air are excluded

      - Patients with fasting serum cholesterol >= 300 mg/dL OR >= 7.75 mmol/L AND
      fasting triglycerides >= 2.5 X upper limit of normal (ULN) should initiate
      lipid-lowering medications with the goal of achieving levels below these
      thresholds

      - No history of intolerance or allergies to octreotide

      - Patients with a history of hypertension must be adequately controlled (baseline
      blood pressure [BP] < 150/90 mm Hg) on antihypertensives

      - No current congestive heart failure (New York Heart Association class II, III, or
      IV)

      - No symptomatic arterial peripheral vascular disease

      - No history of aortic aneurysm, aortic dissection, angina, myocardial infarction,
      stroke, or other arterial thrombotic events within 6 months of registration

      - Eastern Cooperative Oncology Group (ECOG) performance status 0-1

      - Women must not be pregnant or lactating; both men and women of childbearing
      potential must be advised of the importance of using effective birth control
      measures during the course of the study

      - Granulocytes >= 1,500/uL

      - Platelets >= 100,000/uL

      - Creatinine =< 1.5 x upper limit of normal

      - Bilirubin =< 1.5 x upper limit of normal

      - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x
      upper limit of normal (=< 5 x upper limit of normal if liver metastases present)

      - Urine protein =< 1+ OR urine creatinine ratio =< 1 (by urinalysis)

   - If urine protein creatinine (UPC) ratio is > 1 on urinalysis, then 24-hour urine
   collection for protein must be obtained and level must be < 1,000 mg for patient
   enrollment