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.
A Phase II Study of Capecitabine, Temozolomide and Bevacizumab for Metastatic or Unresectable Pancreatic Neuroendocrine Tumors
I. To 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%).
II. Assess the toxicities using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
I. To evaluate progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier analysis.
II. To assess O6-methyl guanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) by central pathology (path) review.
III. To assess serum hormone marker levels. IV. To evaluate computed tomography (CT) Perfusion as a tool to predict early therapeutic response. (Optional) V. To bank serum for future correlative analyses.
Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15, capecitabine orally (PO) twice daily (BID) on days 1-14, and temozolomide PO once daily (QD) on days 10-14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up patients are followed up for 1 year.
Gastrinoma Glucagonoma Insulinoma Pancreatic Polypeptide Tumor Recurrent Islet Cell Carcinoma Recurrent Pancreatic Cancer Somatostatinoma Stage III Pancreatic Cancer Stage IV Pancreatic Cancer Bevacizumab Temozolomide Capecitabine Dacarbazine Antibodies Immunoglobulins Antibodies, Monoclonal
Open to people ages 18 years and up
Laboratory values <= 2 weeks prior to randomization:
Diagnosis of another malignancy, unless the patient was diagnosed at least 3 years earlier and has been disease-free for at least 6 months following the completion of curative intent therapy, specifics as follows:
Known hypersensitivity to capecitabine, temozolomide, or any component of the formulation and or a known deficiency of dihydropyrimidine dehydrogenase.
General Medical Exclusions
Subjects meeting any of the following criteria are ineligible for study entry:
Current, ongoing treatment with full-dose warfarin. However patients may be on stable doses of a low molecular weight heparin are allowed (ie. Lovenox).
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