PRIMARY OBJECTIVES:~Estimate if the combination of capecitabine and temozolomide with bevacizumab for metastatic or unresectable neuroendocrine tumors will improve response rate (RR) by 62% over historical controls (null RR of 40% to true RR 65%).~Assess the toxicities using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.~SECONDARY OBJECTIVES:~Evaluate progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier analysis.~Assess O6-methyl guanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) at baseline by central pathology (path) review.~Assess serum hormone marker levels.~Evaluate computed tomography (CT) Perfusion as a tool to predict early therapeutic response. (Optional)~Bank serum for future correlative analyses.~OUTLINE:~Patients receive bevacizumab intravenously (IV) over 30 to 90 minutes on days 1 and 15, capecitabine orally (PO) twice daily (BID) on days 1 to 14, and temozolomide PO once daily (QD) on days 10 to 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity, with assessment for treatment effect every 3 cycles.~After completion of study treatment, patients are followed up patients are followed long-term for survival.
The purpose of this research is to evaluate the effectiveness and safety of a combination of capecitabine, temozolomide and bevacizumab in the treatment of advanced pancreatic neuroendocrine tumors.