Vaccine Therapy With or Without Cyclophosphamide in Treating Patients Undergoing Chemotherapy and Radiation Therapy for Stage I or Stage II Pancreatic Cancer That Can Be Removed by Surgery

OBJECTIVES:

Primary

• To evaluate the safety and feasibility of a GVAX pancreatic cancer vaccine (GM-CSF gene-transfected allogeneic pancreatic cancer vaccine) when administered alone or in combination with a single intravenous dose or daily metronomic oral doses of cyclophosphamide as neoadjuvant and adjuvant treatment in patients with resectable stage I or II adenocarcinoma of the head, neck, or uncinate process of the pancreas.
• To assess the immune cell infiltrates, particularly T-regulatory cells (Tregs) and CD4+ and CD8+ effector T cells, after neoadjuvant GVAX pancreatic cancer vaccination.
• To assess the changes in the number and function of peripheral mesothelin-specific CD8+ T cells and CD4+, FoxP3+, and GITR+ Tregs after each GVAX pancreatic cancer vaccination when administered alone or in combination with a single dose or metronomic doses of cyclophosphamide.

Secondary

• To estimate disease-free and overall survival of patients treated with these regimens.
• To estimate the effect of immune parameters on disease-free and overall survival of these patients.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

• Arm A: Patients receive GVAX pancreatic cancer vaccine intradermally (ID) on day 1 and undergo pancreaticoduodenectomy on day 15. Approximately 6-10 weeks after surgery, patients receive an additional dose of the vaccine. Beginning approximately 1 month after vaccination, patients receive standard adjuvant chemoradiotherapy comprising gemcitabine, fluorouracil or capecitabine, and radiotherapy over 26-28 weeks. Beginning approximately 4-8 weeks after the completion of chemoradiotherapy, patients receive the vaccine on day 1. Treatment with the vaccine repeats every 28 days for 4 courses.
• Arm B: Patients receive low-dose cyclophosphamide IV on day 0 and GVAX pancreatic cancer vaccine ID on day 1. Patients undergo pancreaticoduodenectomy on day 15. Approximately 6-10 weeks after surgery, patients receive low-dose cyclophosphamide IV on day 0 and the vaccine on day 1. Beginning approximately 1 month after vaccination, patients receive standard adjuvant chemoradiotherapy comprising gemcitabine, fluorouracil or capecitabine, and radiotherapy over 26-28 weeks. Beginning approximately 4-8 weeks after the completion of chemoradiotherapy, patients receive low-dose cyclophosphamide IV on day 0 and the vaccine on day 1. Treatment with cyclophosphamide and the vaccine repeats every 28 days for 4 courses.
• Arm C: Patients receive GVAX pancreatic cancer vaccine ID on day 1 and low-dose oral cyclophosphamide twice daily on days 1-7. Patients undergo pancreaticoduodenectomy on day 15. Approximately 6-10 weeks after surgery, patients receive the vaccine on day 1 and low-dose oral cyclophosphamide twice daily on days 1-7 and 15-21. Beginning approximately 1 month after vaccination, patients receive standard adjuvant chemoradiotherapy comprising gemcitabine, fluorouracil or capecitabine, and radiotherapy over 26-28 weeks. Beginning approximately 4-8 weeks after the completion of chemoradiotherapy, patients receive the vaccine on day 1 and low-dose oral cyclophosphamide twice daily on days 1-7 and 15-21. Treatment with the vaccine and cyclophosphamide repeats every 28 days for 4 courses.

Patients undergo blood sample collection periodically for correlative laboratory studies, including immune cell analysis. Immune cell analysis includes monitoring the quantitative change of peripheral blood lymphocytes, including regulatory T cells (Tregs), and functional analysis of T-cell immune response. Tumor tissue samples collected at the time of surgery are analyzed for tumor antigens and infiltrating immune cells by immunohistochemistry and quantitative real-time PCR.

After completion of study treatment, patients are followed periodically.

DISEASE CHARACTERISTICS:

• Newly diagnosed adenocarcinoma of the head, neck, or uncinate process of the pancreas

• Stage I or II disease
• Surgically resectable disease (R0 or R1) by spiral CT scan

• No distant metastases
• A clear fat plane is present around the celiac and superior mesenteric arteries
• Patent superior mesenteric and portal veins
• Candidate for a pancreaticoduodenectomy

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Hemoglobin ≥ 9 g/dL
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Serum creatinine ≤ 2 mg/dL
• AST and ALT ≤ 2 times upper limit of normal (ULN)
• Amylase ≤ 2 times ULN
• Alkaline phosphatase ≤ 5 times ULN
• Hyperbilirubinemia secondary to tumor-associated extrahepatic biliary obstruction allowed
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 4 weeks after the completion of study treatment
• No history of autoimmune disease, including systemic lupus erythematosus, sarcoidosis, rheumatoid arthritis, glomerulonephritis, or vasculitis
• No uncontrolled medical problems
• No active infections
• No other cancer within the past 5 years except for superficial bladder cancer, nonmelanoma skin cancer, or low-grade prostate cancer not requiring therapy

PRIOR CONCURRENT THERAPY:

• More than 28 days since prior anticancer therapy
• No prior cancer immunotherapy, including the same pancreatic cancer vaccine used in this study
• More than 28 days since prior systemic steroid therapy or immunosuppressive therapy
• No systemic steroid therapy or immunosuppressive therapy during and within 28 days after vaccine administration
• No other concurrent immunotherapy, chemotherapy, radiotherapy, gene therapy, biologic therapy, or investigational therapy for the treatment of pancreatic cancer