GVAX Pancreas Vaccine (With CY) and CRS-207 With or Without Nivolumab
Condition: Previously Treated Metastatic Adenocarcinoma of the Pancreas
MeSH terms: Adenocarcinoma
Intervention: CRS-207; CRS-207; nivolumab; GVAX; CY
Intervention description: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6; 1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6; 3 mg/kg administered IV on Day 1 of Cycles 1-6; 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2; 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2
Intervention MeSH terms: Cyclophosphamide; Nivolumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 93.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to compare the overall survival (OS) of subjects with
      previously treated metastatic pancreatic cancer treated with cyclophosphamide
      (CY)/nivolumab/GVAX pancreas vaccine followed by nivolumab/CRS-207 (Arm A) to subjects
      treated with CY/GVAX pancreas vaccine followed by CRS-207 (Arm B).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥18 years.

          -  Have histologically- or cytologically-proven adenocarcinoma of the pancreas. Patients
             with mixed histology will be excluded.

          -  Have metastatic disease.

          -  Have failed only 1 prior chemotherapy regimen for metastatic pancreatic cancer.

          -  Patients with the presence of at least one measurable lesion.

          -  Patients 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).

          -  ECOG performance status 0 or 1.

          -  Life expectancy of greater than 3 months.

          -  Patients must have adequate organ and marrow function defined by study-specified
             laboratory tests.

          -  Must use acceptable form of birth control while on study.

          -  Ability to understand and willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  known history or evidence of brain metastases.

          -  Had surgery within the last 28 days

          -  Have received any non-oncology vaccine therapy used for prevention of infectious
             diseases including seasonal vaccinations within 28 days of study treatment.

          -  Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, GVAX or CRS-207

          -  Systemic steroids within the last 14 days

          -  Use more than 3 g/day of acetaminophen.

          -  Patients on immunosuppressive agents.

          -  Patients receiving growth factors within the last 14 days

          -  Known allergy to both penicillin and sulfa.

          -  Severe hypersensitivity reaction to any monoclonal antibody.

          -  Have artificial joints or implants that cannot be easily removed

          -  Have any evidence of hepatic cirrhosis or clinical or radiographic ascites.

          -  Have significant and/or malignant pleural effusion

          -  Infection with HIV or hepatitis B or C at screening

          -  Significant heart disease

          -  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

          -  Unable to avoid intimate contact with another individual known to be at high risk of
             listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) during the
             course of CRS-207 treatment until completion of antibiotic regimen.

          -  Are pregnant or breastfeeding.

          -  Have rapidly progressing disease