Avastin, Fluorouracil, Doxorubicin and Streptozocin in Locally Advanced and Metastatic Pancreatic Endocrine Tumors

Inclusion Criteria: * Patients must have locally advanced (unresectable) or metastatic, well or moderately differentiated pancreatic endocrine tumors. * Measurable disease on CT scan or MRI. * Age ≥ 18 years and ≤ 80 years. * Use of effective means of contraception (men and women) in subjects of child-bearing potential * Adequate renal function (serum creatinine ≤1.5, urine protein:creatinine ratio \<1.0 or urine dipstick for proteinuria \< 2+ (patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1 g of protein in 24 hours to be eligible). * Adequate hepatic function (bilirubin ≤2.0, AST and ALT ≤ 3x ULN. * Adequate hematologic function (WBC ≥ 3,000, ANC ≥ 1500, platelets ≥ 100,000) Exclusion Criteria: * Prior therapy with fluorouracil, doxorubicin, streptozocin or avastin * Ejection fraction on MUGA \<50% * ECOG performance status \> 2 * Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored avastin cancer study * Inadequately controlled hypertension (defined as systolic blood pressure \>150 and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications) * Any prior history of hypertensive crisis or hypertensive encephalopathy * Unstable angina * New York Heart Association (NYHA) Grade II or greater congestive heart failure * History of myocardial infarction or unstable angina within 6 months prior to study enrollment * History of stroke or transient ischemic attack within 6 months prior to study enrollment * Significant vascular disease (e.g., aortic aneurysm, aortic dissection) * Symptomatic peripheral vascular disease * Evidence of bleeding diathesis or coagulopathy * Presence of central nervous system or brain metastases * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study * Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment * Pregnant (positive pregnancy test) or lactating. Use of effective means of contraception (men and women) in subjects of child-bearing potential * Proteinuria at screening as demonstrated by either * Urine protein: creatinine (UPC) ratio ≥ 1.0 at screening OR * Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible). * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0 * Evidence of duodenal invasion on CT scan, MRI, or endoscopy * Known hypersensitivity to any component of avastin * Serious, non-healing wound, ulcer, or bone fracture * Inability to comply with study and/or follow-up procedures