This randomized phase II trial is studying bevacizumab to see how well it works compared to cetuximab when given together with gemcitabine, capecitabine, and radiation therapy in treating patients with pancreatic cancer that has been completely removed by surgery. Monoclonal antibodies, such as bevacizumab and cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Cetuximab may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bevacizumab or cetuximab together with gemcitabine, capecitabine, and radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether bevacizumab is more effective than cetuximab when given together with gemcitabine, capecitabine, and radiation therapy in treating pancreatic cancer.

PRIMARY OBJECTIVES:

I. To describe the toxicity profile of cetuximab and bevacizumab when combined with gemcitabine, before and after capecitabine plus radiation and during capecitabine plus radiation in patients with completely-resected pancreatic carcinoma in the adjuvant setting.

II. To assess the safety profile of either cetuximab or bevacizumab plus gemcitabine in patients with resected pancreatic cancer.

III. To obtain tissue specimens from resections of patients enrolled on study for correlative studies and further evaluations.

SECONDARY OBJECTIVES:

I. To evaluate disease-free and overall survival for patients receiving either cetuximab or bevacizumab in combination with gemcitabine before and after capecitabine plus radiation.

II. To assess the safety profile for patients receiving either capecitabine plus cetuximab plus radiation, or capecitabine plus bevacizumab plus radiation.

III. To correlate changes in serum amphiregulin and TGF alpha to survival, DFS and rash for patients receiving cetuximab.

IV. To determine the 2-year survival rate for patients receiving either cetuximab plus gemcitabine before and after capecitabine plus cetuximab plus radiation, or bevacizumab plus gemcitabine before and after capecitabine plus bevacizumab plus radiation.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to degree of prior resection of the pancreatic tumor (R0 vs R1). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive cetuximab IV over 60-120 minutes on day 1, once weekly, in weeks 1-24; gemcitabine hydrochloride IV over 30 minutes on day 1, once weekly, in weeks 1-3, 13-15, 17-19, and 21-23; oral capecitabine twice daily on days 1-5, 5 days a week, in weeks 5-10. Patients also undergo radiotherapy once daily, 5 days a week, beginning in week 5 and continuing for approximately 5½ weeks (25 fractions).

Arm II: Patients receive bevacizumab IV over 60-90 minutes on day 1 in weeks 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, and 23. Patients also receive gemcitabine hydrochloride and capecitabine and undergo radiotherapy as in arm I.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 3 years.

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed evidence of pancreatic carcinoma

• Patients must have had all gross disease resected (R0 or R1 resection)

• Patients undergoing an R2 resection are not eligible

• Patients must have had no prior chemotherapy or radiation therapy for pancreatic cancer and must have had no prior EGFR/VEGF inhibition

• Patient must have ECOG performance status of 0-2

• Leukocytes >= 3,000/μL

• ANC >= 1,500/μL

• Platelets >= 100,000/μL

• Total bilirubin Within normal institutional limits

• AST (SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal

• Creatinine clearance >= 60 mL/min for patients with creatinine levels above institutional normal

• Patients must be > 4 weeks and =< 8 weeks post-surgery at time of study registration (may be up to 10 weeks post-surgery prior to start of study therapy)

• Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception prior to study entry

• Women must not be pregnant or breast-feeding; all agents used in this study as well as radiation therapy to the abdomen have the potential for teratogenic or abortifacient effects; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy

• Patients must not be receiving any other investigational agents

• Patients with known metastases are not eligible

• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab, bevacizumab or other agents used in the study are not eligible

• Patients with wounds that have not fully healed are not eligible

• Patients must not have cardiac arrhythmia

• Patients must have no known HIV infection

• Patients must not have any of the following: acinar cell carcinoma, neuroendocrine carcinoma, cystadenocarcinoma, carcinosarcoma

• Patients with psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude them from meeting the study requirements are not eligible

• Patients requiring full dose anticoagulation are not eligible

• Patients with a history of transient ischemic attack (TIA) or cerebrovascular accident (CVA) are not eligible

• Patients with a history of the following within twelve months of study entry are not eligible:

  • Arterial thrombembolic events
  • Unstable angina
  • Myocardial infarction