A Trial of Boost Vaccinations of Pancreatic Tumor Cell Vaccine

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and feasibility of long term boost vaccination of a lethally irradiated, allogenic pancreatic tumor cell vaccine transfected with the granulocyte macrophage colony-stimulating factor (GM-CSF) gene alone or given in combination with either a single intravenous dose or daily metronomic oral doses of cyclophosphamide for the treatment of patients with surgically resected adenocarcinoma of the head, neck, tail or the uncinate process of the pancreas.

Detailed Description
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Primary Objective: 1. To evaluate the safety and feasibility of long term boost vaccinations of a lethally irradiated, allogeneic pancreatic tumor cell vaccine transfected with the GM-CSF gene given alone or in combination with either a single intravenous dose or daily metronomic oral doses of cyclophosphamide for the treatment of patients with surgically resected adenocarcinoma of the head, neck, or uncinate process of the pancreas. Secondary Objective: To assess the effect of boost vaccinations and long-term treatment of immune modulating doses of cyclophosphamide on the number, repertoire and avidity of peripheral mesothelin-specific CD8+ T cells. To estimate disease-free and overall survival of surgically resected pancreatic adenocarcinoma patients treated with vaccine boosts with or without low dose cyclophosphamide.

Official Title
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A Safety and Feasibility Trial of Boost Vaccinations of a Lethally Irradiated, Allogeneic Pancreatic Tumor Cell Vaccine Transfected With the GM-CSF Gene

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Biological: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a history of surgically resected and pathologically proved AJCC stage I or stage II adenocarcinoma of the head, neck, or uncinate of the pancreas. Cohorts 1, 3, 4 and 5: Have been a participant in Hopkins IRB protocol J0810, J1568, J15237 or J1766. Cohort 2: Have never received any type of pancreatic cancer vaccine/immunotherapy, had the Whipple surgery within 18 months and completed the planned adjuvant chemotherapy and/or chemoradiation. Cohorts 1, 3, 4 and 5: Received the last irradiated GM-CSF transfected allogeneic pancreatic cell lines Panc 10.05 and Panc 6.03 at least 6-12 months prior. Has received the last anti-cancer therapy at least 28 days ago. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Has provided informed consent. Has adequate hematologic function.(Hemoglobin ≥ 9 g/dL ANC ≥ 1500/mm3 Platelets ≥ 100,000 K/ mm3). Has adequate renal function (Serum creatinine ≤ 2 mg/dL). Has adequate hepatic function. (Bilirubin ≤ 2.0 mg/dl, unless known Gilbert's Syndrome; AST, ALT and amylase ≤ 2x upper limit of normal, Alk Phos ≤ 5x upper limit of normal). Agree to use adequate birth control, if of childbearing potential. Exclusion Criteria: Has radiographic evidence of pancreatic cancer recurrence. Has any documented history of autoimmune diseases including systemic lupus erythematosus, sarcoidosis, rheumatoid arthritis, glomerulonephritis,or vasculitis. Has any uncontrolled medical problems. Has had systemic steroid therapy within 28 days before vaccine administration. Has an anticipated need for systemic steroid therapy within 28 days after vaccine administration. Has any evidence of active infections. Is pregnant. Has a history of another cancer (other than pancreatic cancer) or myeloproliferative disorders in the past five years except for treated non-melanoma skin cancer, superficial bladder cancer, or carcinoma in-situ of the cervix. Has a history of noncompliance during previous vaccination cycles with study treatment and/or monitoring which is concerning for continued noncompliance.

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
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort 1<br>Arm A: Vaccine only. Arm B receives vaccine as well as a single dose of intravenous cyclophosphamide. Arm C: In addition to Vaccine Cohort 3 receives a daily dose of metronomic cyclophosphamide orally. Only patients from the J0810 study are eligible. Closed to enrollment. | Biological: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine.<br>* A pancreatic vaccine secreting a granulocyte-macrophage colony-stimulating factor(GM-CSF). The vaccine consists of equal numbers of pancreatic cancer cells (Panc 6.03)and (Panc. 10.05) into a single vaccine. The vaccine is administered every 6 months.<br>* Other names: Cyclophosphamide;|
| Other: Cohort 2<br>Cohort 2 receives vaccine as well as a single dose of intravenous cyclophosphamide. Vaccine-naïve cohort. Closed to enrollment. | Biological: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine.<br>* A pancreatic vaccine secreting a granulocyte-macrophage colony-stimulating factor(GM-CSF). The vaccine consists of equal numbers of pancreatic cancer cells (Panc 6.03)and (Panc. 10.05) into a single vaccine. The vaccine is administered every 6 months.<br>* Other names: Cyclophosphamide;|
| Other: Cohort 3<br>Cohort 3 receives vaccine as well as a single dose of intravenous cyclophosphamide. Only participants from J1568 study are eligible. | Biological: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine.<br>* A pancreatic vaccine secreting a granulocyte-macrophage colony-stimulating factor(GM-CSF). The vaccine consists of equal numbers of pancreatic cancer cells (Panc 6.03)and (Panc. 10.05) into a single vaccine. The vaccine is administered every 6 months.<br>* Other names: Cyclophosphamide;|
| Other: Cohort 4<br>Cohort 4 receives vaccine as well as a single dose of intravenous cyclophosphamide. Only participants from J15237 study are eligible. | Biological: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine.<br>* A pancreatic vaccine secreting a granulocyte-macrophage colony-stimulating factor(GM-CSF). The vaccine consists of equal numbers of pancreatic cancer cells (Panc 6.03)and (Panc. 10.05) into a single vaccine. The vaccine is administered every 6 months.<br>* Other names: Cyclophosphamide;|
| Other: Cohort 5<br>Cohort 5 receives vaccine as well as a single dose of intravenous cyclophosphamide. Only participants from J1766 study are eligible. | Biological: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine.<br>* A pancreatic vaccine secreting a granulocyte-macrophage colony-stimulating factor(GM-CSF). The vaccine consists of equal numbers of pancreatic cancer cells (Panc 6.03)and (Panc. 10.05) into a single vaccine. The vaccine is administered every 6 months.<br>* Other names: Cyclophosphamide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free overall survival. | Safety as measured by local and systemic toxicity according to NCI CTCAE v 3.0 | total of 13 years with 6 months between vaccines. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adenocarcinoma, Cyclophosphamide, Immunotherapy, Neo-Adjuvant, Pancreatic tumor vaccine, GM-CSF, Randomize