Study With CY, Pembrolizumab, GVAX Pancreas Vaccine, and SBRT in Patients With Locally Advanced Pancreatic Cancer
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: Cyclophosphamide; GVAX Pancreatic Cancer Vaccine; Pembrolizumab; SBRT
Intervention description: 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.; 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.; 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.; Patients will receive SBRT (6.6 Gy for 5 days) with the second dose of combined immunotherapy (CY/Pembrolizumab/GVAX Pancreas Vaccine).
Intervention MeSH terms: Cyclophosphamide; Pembrolizumab; Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 58.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: vaccine; immunotherapy; antibody; PD-1; radiation

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Locally advanced pancreatic adenocarcinoma

          2. 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.

          3. Age >18 years

          4. No metastatic disease

          5. ECOG Performance Status of 0 to 1

          6. Adequate organ function as defined by study-specified laboratory tests

          7. Patients must be able to have fiducials placed for SBRT

          8. Must use acceptable form of birth control through the study

          9. Signed informed consent form

         10. Willing and able to comply with study procedures

        Exclusion Criteria:

          1. Patients who have been off of mFOLFIRINOX or gemcitabine/abraxane therapy for more
             than 49 days

          2. Patients who have had more than one line of chemotherapy

          3. 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

          4. 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

          5. Patients receiving active immunosuppressive agents or chronic use of systemic
             corticosteroids within 14 days prior to first dose of study drug

          6. 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

          7. 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.

          8. Patients who have known history of infection with HIV, hepatitis B, or hepatitis C

          9. Patients with evidence of interstitial lung disease

         10. Patients on home oxygen

         11. Patients with oxygen saturation of <92% on room air by pulse oximetry

         12. Pregnant or lactating

         13. Conditions, including alcohol or drug dependence, or intercurrent illness that would
             affect the patient's ability to comply with study visits and procedures