Vaccine Therapy Combined With Adjuvant Chemoradiotherapy in Treating Patients With Resected Stage I or Stage II Adenocarcinoma (Cancer) of the Pancreas

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Biological: GVAX pancreatic cancer vaccine


Participation Criteria
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Eligibility Criteria
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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 Sjogren'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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GVAX pancreatic cancer vaccine<br>5E8 vaccine cells. The first vaccination is administered 6-8 weeks after surgery. Four to eight weeks following the completion of the last cycle of adjuvant radiation and chemotherapy (chemo-radiation therapy is standard of care and not part of the protocol) eligible patients will receive three additional vaccinations at one month intervals. Patients who continue to remain disease-free will receive a fifth booster vaccination, six months following the fourth vaccination | Biological: GVAX pancreatic cancer vaccine<br>* Patients will receive vaccinations consisting of 5E8 vaccine cells. The first vaccination is administered 6-8 weeks after surgery. Four to eight weeks following the completion of the last cycle of adjuvant radiation and chemotherapy (chemo-radiation therapy is standard of care and not part of the protocol) eligible patients will receive three additional vaccinations at one month intervals. Patients who continue to remain disease-free will receive a fifth booster vaccination, six months following the fourth vaccination.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival in patients treated with adjuvant chemoradiotherapy in sequence with the irradiated allogeneic GM-CSF transfected pancreatic tumor cell lines. Overall survival is defined as time from surgery until death, regardless of cause. | Participants were followed for the duration of the study, an average of 2 years | 
| Disease-free Survival | Disease-free Survival in Patients Treated With Adjuvant Chemoradiotherapy in Sequence With the Irradiated Allogeneic GM-CSF Transfected Pancreatic Tumor Cell Lines. DFS is defined as time from surgery until clinical evidence of disease (eg, CT scan) or death due to any cause. | Participants were followed for the duration of the study, an average of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Further Identify and Characterize Toxicities Associated With Intradermal Injections of the Vaccine That Were Initially Reported in the Phase 1 Trial. |  | 4 years | 
| Estimate the Association of Specific in Vivo Parameters of Immune Response With Clinical Responses in Patients Treated With Combination Chemoradiotherapy Together With the Irradiated Allogeneic GM-CSF Transfected Pancreatic Tumor Cell Lines. | The specific immune parameters include: post-vaccination delayed type hypersensitivity reactions to autologous tumor and the degree of local eosinophil, macrophage, and T cell infiltration at the vaccine site, and mesothelin-specific T cell responses. | Continuous | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I pancreatic cancer, stage II pancreatic cancer, duct cell adenocarcinoma of the pancreas