GVAX Pancreas Vaccine (With CY) in Combination With Nivolumab and SBRT for Patients With Borderline Resectable Pancreatic Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety and clinical activity of FOLFIRINOX along with a whole cell vaccine with immune modulating doses of cyclophosphamide and nivolumab combined with Stereotactic Body Radiation Therapy (SBRT) in patients with pancreatic cancer.

Official Title
-----------------
A Phase II Clinical Trial of GVAX Pancreas Vaccine (With Cyclophosphamide) in Combination With Nivolumab and Stereotactic Body Radiation Therapy (SBRT) Followed by Definitive Resection for Patients With Borderline Resectable Pancreatic Adenocarcinoma

Conditions
-----------------
Pancreatic Cancer

Intervention / Treatment
-----------------
* Drug: Cyclophosphamide
* Drug: Nivolumab
* Drug: GVAX Pancreas Vaccine
* Radiation: Stereotactic Body Radiation (SBRT)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have histologically proven pancreatic cancer that is borderline resectable No more than 1 month/cycle (28 days) of systemic therapy for pancreatic cancer Age >18 years old. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Patients must have adequate organ and marrow function defined by study-specified laboratory tests. Woman of child bearing potential must have a negative pregnancy test. Must use an acceptable form of birth control while on study. Must be candidate for Stereotactic Body Radiation Therapy (SBRT) Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Had major surgery within the last 28 days Had an investigational drug or device within the past 28 days Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, etc) Completed more than 1 month/cycle (28 days) of chemotherapy for pancreas cancer Patient on an immunosuppressive systemic treatment, such as steroids, in the past 2 years. Other cancer diagnosis requiring treatment within two years History of allergic reactions related to the drugs (Nivolumab, Cyclophosphamide, GM-hetastarch, corn, dimethyl sulfoxide, fetal bovine serum, trypsin (porcine origin), yeast or any other component of the GVAX vaccine) in this study. Patients receiving growth factors within the last 14 days. Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, psychological, immune or other medical conditions. Pregnant or breastfeeding. Have known history of infection with HIV, hepatitis B, or hepatitis C. Unwilling or unable to follow the study schedule for any reason. Presence of tissue or organ allograft, regardless of need for immunosuppression (including corneal allograft) Squamous pancreatic cancer or adenosquamous pancreatic cancer with malignant squamous cells >30%

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CY, Nivolumab, GVAX, and SBRT<br>CY, Nivolumab, GVAX, and SBRT | Drug: Cyclophosphamide<br>* Cyclophosphamide 200 mg/m2 will be administered one day prior to vaccination (day 0). First dose will be given within 4 to 6 weeks after chemotherapy. 3 weeks after the first dose of immunotherapy the second dose will be given.<br>* Other names: CY;Drug: Nivolumab<br>* Nivolumab (240 mg) will be administered one day prior to vaccination. First dose will be given within 4 to 6 weeks after chemotherapy. 3 weeks after the first dose of immunotherapy the second dose will be given.<br>* Other names: OPDIVO;Drug: GVAX Pancreas Vaccine<br>* Vaccine will be administered one day after cyclophosphamide and nivolumab. 3 weeks after the first dose of immunotherapy the second dose will be given.<br>* Other names: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1/GM-Neo vaccine;Radiation: Stereotactic Body Radiation (SBRT)<br>* SBRT (6.6 Gy over 5 days) will be started during the second dose of immunotherapy (3 weeks after the first dose of immunotherapy).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD8 count (cells/mm^3) in the tumor microenvironment | Whether the CD8 count in the tumor microenvironment is higher for patients with BR-PDAC treated with neoadjuvant chemotherapy, SBRT, and Cy/GVAX/nivolumab immunotherapy as compared to archived samples from patients treated with FOLFIRINOX and SBRT. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic complete response (pCR) rate at surgical resection | Pathologic complete response (pCR) rate at surgical resection of BR-PDAC treated with neoadjuvant sequential chemotherapy, SBRT, and Cy/GVAX/nivolumab immunotherapy. | 4 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Neoadjuvant therapy, immunotherapy, Cytoxan, Cyclophosphamide, Pancreatic Vaccine, SBRT, GVAX, Nivolumab, borderline resectable, Radioimmunotherapy, Vaccine, Antibody, Anti-PD-1