Study With CY, Pembrolizumab, GVAX Pancreas Vaccine, and SBRT in Patients With Locally Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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This study will be looking at whether combining cyclophosphamide, pembrolizumab (an antibody that blocks negative signals to T cells), GVAX (pancreatic cancer vaccine), and SBRT (focused radiation) is effective (anti-tumor activity) and safe in patients with locally advanced pancreatic cancer.

Official Title
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A Phase II Study of GM-CSF Secreting Allogeneic Pancreatic Cancer Vaccine in Combination With PD-1 Blockade Antibody (Pembrolizumab) and Stereotactic Body Radiation Therapy (SBRT) for the Treatment of Patients With Locally Advanced Adenocarcinoma of the Pancreas

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: GVAX Pancreatic Cancer Vaccine
* Drug: Pembrolizumab
* Radiation: SBRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally advanced pancreatic adenocarcinoma Patients must have received mFOLFIRINOX or Gemcitabine/ Abraxane based chemotherapy for 4 cycles with last dose of therapy between 2-5 weeks of study enrollment. Age >18 years No metastatic disease ECOG Performance Status of 0 to 1 Adequate organ function as defined by study-specified laboratory tests Patients must be able to have fiducials placed for SBRT Must use acceptable form of birth control through the study Signed informed consent form Willing and able to comply with study procedures Exclusion Criteria: Patients who have been off of mFOLFIRINOX or gemcitabine/abraxane therapy for more than 49 days Patients who have had more than one line of chemotherapy Patients with uncontrolled intercurrent illness, including but not limited to ongoing or active infection, systematic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric condition that would limit compliance with study requirements Patient who have had prior treatment with IL-2, interferon, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, or anti-CTLA-4 antibodies Patients receiving active immunosuppressive agents or chronic use of systemic corticosteroids within 14 days prior to first dose of study drug Patients who have received growth factors, including but not limited to granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 14 days of study drug administration Patients with history of any autoimmune disease:inflammatory bowel disease, (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematous (SLE) autoimmune vasculitis, CNS or motor neuropathy considered to be of autoimmune origin. Patients who have known history of infection with HIV, hepatitis B, or hepatitis C Patients with evidence of interstitial lung disease Patients on home oxygen Patients with oxygen saturation of <92% on room air by pulse oximetry 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

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: Cyclophosphamide, Pembrolizumab, GVAX Pancreas Vaccine, SBRT<br> | Drug: Cyclophosphamide<br>* 200 mg/m2 is to be administered as a 30 minute IV infusion one day prior to GVAX Pancreas Vaccine every 21 days for a total of 8 doses. In the extended treatment phase, eligible patients may receive 200 mg/m2 as a 30 minute IV infusion one day prior to GVAX Pancreas Vaccine every 6 months for an additional 4 doses.<br>* Other names: CY;Drug: GVAX Pancreatic Cancer Vaccine<br>* 2.5E8 cells of each cell line (Panc 6.03/Panc 10.05) for a total of 5E8 cells is to be administered one day after CY and pembrolizumab for a total of 8 doses. In the extended treatment phase, eligible patients may receive 2.5E8 cells of each cell line (Panc 6.03/Panc 10.05) for a total of 5E8 cells administered one day after CY every 6 months for an additional 4 doses.<br>* Other names: Panc 10.05 pcDNA1/GM-Neo, Panc 6.03 pcDNA1/GM-Neo;Drug: Pembrolizumab<br>* 200 mg will be administered as a 30 minute IV infusion one day prior to the GVAX pancreas vaccine every 21 days for a total of 8 doses. In the extended treatment phase, eligible patients may receive 200 mg as a 30 minute IV infusion every 21 days for an additional 9 doses.<br>* Other names: KEYTRUDA;Radiation: SBRT<br>* Patients will receive SBRT (6.6 Gy for 5 days) with the second dose of combined immunotherapy (CY/Pembrolizumab/GVAX Pancreas Vaccine).<br>* Other names: Stereotactic Body Radiation Therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distant Metastasis Free Survival (DMFS) | DMFS is defined as the duration of time from start of treatment to identification of distant metastases on imaging or death, whichever occurs first. Estimation based on the Kaplan-Meier curve. | 62 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing a Grade 3 or Above Treatment Related Toxicities | When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject. | 41 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccine, immunotherapy, antibody, PD-1, radiation