Study of CRS-207, Nivolumab, and Ipilimumab With or Without GVAX Pancreas Vaccine (With Cy) in Patients With Pancreatic Cancer
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: Cyclophosphamide; Nivolumab; Ipilimumab; GVAX Pancreas Vaccine; CRS-207; CRS-207
Intervention description: Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Cyclophosphamide (200 mg/m2) will be administered IV on day 1 of Cycles 1 and 2.; Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Nivolumab (360 mg) will be administered IV on day 1 of Cycles 1-6.; Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Ipilimumab (1 mg/kg) will be administered IV on Day 1 of Cycles 1, 3, and 5.; Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Vaccine will be administered on Day 2 of Cycles 1 and 2.; Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). CRS-207 (1 × 109 CFU) will be administered IV on Day 2 of Cycles 3-6.; Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). CRS-207 (1 × 109 CFU) will be administered IV on Day 2 of Cycles 1-6.
Intervention MeSH terms: Cyclophosphamide; Nivolumab; Ipilimumab; Pancrelipase; Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 61.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CY; Cyclophosphamide; Pancreatic Vaccine; GVAX; Nivolumab; Vaccine; Ipilimumab; CRS-207; Immunotherapy; PD-1; Adenocarcinoma; Carcinoma; Neoplasms

Summary:

      The purpose of this study is to study the safety and clinical activity of nivolumab and
      ipilimumab in combination with either sequential administration of CY/GVAX pancreas vaccine
      followed by CRS-207 (Arm A) or with administration of CRS-207 alone (Arm B) in patients with
      pancreatic cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age ≥18 years.

          2. Have histologically or cytologically proven adenocarcinoma of the pancreas.

          3. Have metastatic disease.

          4. Have disease progression.

          5. Patients with the presence of at least one measurable lesion.

          6. Patient's acceptance to have a tumor biopsy of an accessible lesion at baseline and on
             treatment if the lesion can be biopsied with acceptable clinical risk (as judged by
             the investigator).

          7. ECOG performance status 0 or 1

          8. Life expectancy of greater than 3 months.

          9. Patients must have adequate organ and marrow function defined by study-specified
             laboratory tests.

         10. Must use acceptable form of birth control while on study.

         11. Ability to understand and willingness to sign a written informed consent document.

        Exclusion Criteria:

          1. Known history or evidence of brain metastases.

          2. Had surgery within the last 28 days

          3. Had chemotherapy, radiation, or biological cancer therapy within the last 14 days

          4. Have received a prophylactic vaccine within 14 days or received a live vaccine within
             30 days of planned start of study therapy.

          5. Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2,or anti-CTLA4

          6. Systemic steroids within the last 14 days

          7. Use more than 2 g/day of acetaminophen.

          8. Patients on immunosuppressive agents.

          9. Patients receiving growth factors within the last 14 days

         10. Known allergy to both penicillin and sulfa.

         11. Severe hypersensitivity reaction to any monoclonal antibody.

         12. Have artificial joints or implants that cannot be easily removed

         13. Have any evidence of clinical or radiographic ascites.

         14. Have significant and/or malignant pleural effusion

         15. Have had a new pulmonary embolism, extremity deep venous thromboembolism, or portal
             vein thrombosis within 2 months of study treatment

         16. Infection with HIV or hepatitis B or C at screening

         17. Significant heart disease

         18. Conditions, including alcohol or drug dependence, intercurrent illness, or lack of
             sufficient peripheral venous access, that would affect the patient's ability to comply
             with study visits and procedures

         19. Are pregnant or breastfeeding.

         20. Have rapidly progressing disease