Official Title: “A Safety and Efficacy Trial of Lethally Irradiated Allogeneic Pancreatic Tumor Cells Transfected With the GM-CSF Gene in Combination With Adjuvant Chemoradiotherapy for the Treatment of Adenocarcinoma of the Pancreas”

RATIONALE: Vaccines made from gene-modified pancreatic cancer cells may make the body build an immune response to kill tumor cells. Drugs used in chemotherapy, such as fluorouracil, work in different ways to stop tumor cells from dividing so they stop growing or die.

Radiation therapy uses high-energy x-rays to damage tumor cells. Giving vaccine therapy together with chemotherapy and radiation therapy after surgery may kill any remaining tumor cells.

PURPOSE: This phase II trial is studying how well giving vaccine therapy together with adjuvant chemoradiotherapy works in treating patients with resected stage I or stage II adenocarcinoma (cancer) of the pancreas.

Study Type: Interventional

Study Design: Treatment, Open Label

OBJECTIVES:

Primary - Determine overall and disease-free survival of patients with resected stage I or II adenocarcinoma of the pancreas treated with adjuvant chemoradiotherapy in combination with GVAX pancreatic cancer vaccine.

Secondary - Correlate specific in vivo parameters of immune response (post-vaccination delayed-type hypersensitivity reactions to autologous tumor, mesothelin-specific T-cell response, and the degree of local eosinophil, macrophage, and T-cell infiltration at the vaccine site) with clinical responses in patients treated with this regimen. - Determine the toxic effects associated with intradermal injections of this vaccine in these patients.

OUTLINE: This is an open-label study. - Post surgery vaccination: Within 8-10 weeks after pancreaticoduodenectomy, patients receive GVAX pancreatic cancer vaccine intradermally (ID) on day 0. - Adjuvant chemoradiotherapy: Within 16-28 days after the first vaccination, patients receive fluorouracil (5-FU) IV continuously for 3 weeks. Approximately 1-2 weeks after completion of 5-FU, patients receive chemoradiotherapy comprising radiotherapy daily and 5-FU IV continuously for 26-28 weeks. Approximately 3-5 weeks after completion of chemoradiotherapy, patients receive 5-FU IV continuously for 4 weeks. 5-FU repeats every 6 weeks for 2 courses. - Post chemoradiotherapy vaccination: Within 4-8 weeks after the completion of chemoradiotherapy, patients receive GVAX pancreatic cancer vaccine ID on days 0, 28, 56, and 196.

Treatment continues in the absence of unacceptable toxicity.

Patients are followed every 3 months for 1 year and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: GVAX pancreatic cancer vaccine
• Drug: fluorouracil
• Procedure: adjuvant therapy
• Procedure: radiation therapy

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive ductal adenocarcinoma of the head, neck, and uncinate process of the pancreas
• Mixed adenocarcinoma tumors allowed if the predominant invasive component of the tumor is adenocarcinoma
• Stage I or II (clinical stage T1-3, N0-1, M0) disease
• Has undergone pancreaticoduodenectomy at the Johns Hopkins Hospital within the past 8-10 weeks
• Completely resected (R0) or microscopic residual (R1) disease
• No diagnosis other than ductal adenocarcinoma, including any of the following:
• Adenosquamous
• Squamous cell
• Colloid
• Islet cell
• Non-invasive intraductal papillary mucinous neoplasms
• Serous or mucinous cystadenoma or cystadenocarcinoma
• Carcinoid
• Small or large cell carcinoma
• Intraductal oncocytic papillary neoplasms
• Osteoclast-like giant cell tumors
• Acinar cell carcinoma
• Pancreatoblastoma
• Solid pseudopapillary tumors
• Undifferentiated small cell carcinoma
• Non-epithelial tumors (sarcoma, gastrointestinal stromal tumor, or lymphoma)
• Adenocarcinoma of the ampulla
• Adenocarcinoma of the distal bile duct
• Adenocarcinoma of the duodenum
• No recurrent disease
• No metastatic disease, including peritoneal implants or liver and/or lung involvement

PATIENT CHARACTERISTICS:

• Age
• 18 and over
• Performance status
• ECOG 0-1
• Life expectancy
• Not specified
• Hematopoietic
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL
• Hepatic
• Bilirubin ≤ 2 mg/dL
• AST/ALT ≤ 2 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 5 times ULN
• Renal
• Creatinine ≤ 2 mg/dL
• Pulmonary
• No asthma or chronic obstructive pulmonary disease requiring systemic corticosteroids
• Immunologic
• HIV negative
• No active infection
• No prior or concurrent autoimmune disease requiring treatment with systemic immunosuppressants, including any of the following:
• Inflammatory bowel disease
• Systemic vasculitis
• Scleroderma
• Psoriasis
• Multiple sclerosis
• Hemolytic anemia or immune thrombocytopenia
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Sjögren's syndrome
• Sarcoidosis
• Negative results to viral delayed-type hypersensitivity serology testing if autologous tumor cells are available
• Other
• No postoperative complications (e.g., inability to take oral nutrition ≥ 1,500 calories/day, ongoing requirement for long-term biliary stenting, or persistence of wound infection)
• No other malignancy within the past 5 years except nonmelanoma skin cancer
• No uncontrolled medical conditions that would preclude study participation
• No other major active medical or psychosocial problem that could be exacerbated by study treatment
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 4 weeks after study participation

PRIOR CONCURRENT THERAPY:

• Biologic therapy
• More than 1 month since prior biologic therapy
• No other concurrent biologic therapy, immunotherapy, or gene therapy for pancreatic cancer
• Chemotherapy
• More than 1 month since prior chemotherapy
• No other concurrent chemotherapy for pancreatic cancer
• Endocrine therapy
• More than 28 days since prior systemic steroids
• No concurrent systemic corticosteroids
• Radiotherapy
• More than 1 month since prior radiotherapy
• No other concurrent radiotherapy for pancreatic cancer
• Surgery
• See Disease Characteristics
• Recovered from prior surgery
• Other
• More than 1 month since prior participation in an investigational new drug trial
• No other concurrent investigational therapy for pancreatic cancer

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center

Overall Clinical Trial Officials and Contacts

Daniel A. Laheru, MD Principal Investigator Sidney Kimmel Comprehensive Cancer Center  

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00084383

Study ID Number: CDR0000361806

ClinicalTrials.gov Identifier: NCT00084383

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database