Pancreatic Tumor Cell Vaccine (GVAX), Low Dose Cyclophosphamide, Fractionated Stereotactic Body Radiation Therapy (SBRT), and FOLFIRINOX Chemotherapy in Patients With Resected Adenocarcinoma of the Pancreas

Study Overview
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Brief Summary
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The purpose of this study is to estimate safety of a whole cell vaccine with immune modulating doses of cyclophosphamide followed by SBRT and FOLFIRINOX chemotherapy in pancreatic cancer patients after surgery.

Official Title
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Pilot Study Evaluating An Allogeneic GM-CSF-Transduced Pancreatic Tumor Cell Vaccine (GVAX) and Low Dose Cyclophosphamide Integrated With Fractionated Stereotactic Body Radiation Therapy (SBRT) and FOLFIRINOX Chemotherapy in Patients With Resected Adenocarcinoma of the Pancreas

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Cyclophosphamide
* Biological: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1/GM-Neo vaccine
* Radiation: Stereotactic Body Radiation (SBRT)
* Drug: FOLFIRINOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (abbreviated): Documented cancer of the pancreas (head, neck, and/or uncinate process), that has been completely resected No prior Chemotherapy, radiation therapy or biologic therapy for pancreatic cancer Must be within 10 weeks from surgical resection of cancer Titanium clips (minimum 1) must be placed at the time of surgery to aid in SBRT treatment planning ECOG Performance Status of 0 to 1 Adequate organ function as defined by study-specified laboratory tests Must use acceptable form of birth control through the study and for 28 days after final dose of study drug Signed informed consent form Willing and able to comply with study procedures Exclusion criteria (abbreviated): Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, immune or other medical conditions Presence of metastatic disease Clinical metabolic or laboratory abnormalities defined as Grade 3 or 4 of the National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 Systemically active steroids Chemotherapy, radiation therapy or biologic therapy within 28 days prior to receiving study drug Inability to begin protocol treatment within 70 days (10 weeks) after surgery to remove cancer History of HIV, hepatitis B or C infection Pregnant or lactating Conditions, including alcohol or drug dependence, or intercurrent illness that would affect the patient's ability to comply with study visits and procedures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 76 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SBRT and FOLFIRINOX<br>The first 6 patients will receive SBRT and FOLFIRINOX only. | Radiation: Stereotactic Body Radiation (SBRT)<br>* SBRT (6.6 Gy) will be administered over 5 days starting between 13-17 days after the first vaccine dose (Arm 2) or within 6-10 weeks of surgery (Arm 1).<br>Drug: FOLFIRINOX<br>* FOLFIRINOX will be administered over 6 cycles starting at least 14 days after SBRT (Arms 1 and 2) and at least 28 days after the first vaccine (Arm 2).<br>* Other names: Fluorouracil;|
| Experimental: Cyclophosphamide, Vaccine, SBRT, and FOLFIRINOX<br>The last 12 patients will receive cyclophosphamide, Vaccine, SBRT, and FOLFIRINOX. | Drug: Cyclophosphamide<br>* Cyclophosphamide 200 mg/m2 will be administered one day prior to vaccination (day 0). One dose will be given prior to SBRT and FOLFIRINOX and four additional doses after FOLFIRINOX completion for a total of 5 doses. Additional Cy-vaccine boosts may be given every 6 months thereafter until disease recurrence.<br>* Other names: Cytoxan;Biological: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1/GM-Neo vaccine<br>* Vaccine will be administered one day after cyclophosphamide (day 1). One dose will be given prior to SBRT and FOLFIRINOX and four additional doses after FOLFIRINOX completion for a total of 5 doses. Additional Cy-vaccine boosts may be given every 6 months thereafter until disease recurrence.<br>* Other names: Pancreatic cancer vaccine;Radiation: Stereotactic Body Radiation (SBRT)<br>* SBRT (6.6 Gy) will be administered over 5 days starting between 13-17 days after the first vaccine dose (Arm 2) or within 6-10 weeks of surgery (Arm 1).<br>Drug: FOLFIRINOX<br>* FOLFIRINOX will be administered over 6 cycles starting at least 14 days after SBRT (Arms 1 and 2) and at least 28 days after the first vaccine (Arm 2).<br>* Other names: Fluorouracil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events as a measure of toxicity | To determine the safety profile of the whole cell vaccine (GVAX) administered along with cyclophosphamide; fractionated SBRT, and FOLFIRINOX. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | To estimate the median overall survival (OS), disease-free survival (DFS), and distant metastases free survival (DMFS) using Kaplan-Meier techniques. | 4 years | 
| Time to disease progression using immune correlates | Correlate progression with the immune response through vaccine-induced changes in the number, function, avidity, size and diversity of the mesothelin-specific T cell repertoire). | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stereotactic radiation therapy, FOLFIRINOX, Adjuvant therapy, Immunotherapy, Cytoxan, Cyclophosphamide, Pancreatic Vaccine, SBRT