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GVAX Pancreas Vaccine (With CY) and CRS-207 With or Without Nivolumab

Phase 2
Completed
Conditions
Previously Treated Metastatic Adenocarcinoma of the Pancreas
Interventions
Biological: CRS-207
Biological: GVAX
Registration Number
NCT02243371
Lead Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Brief 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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
93
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm A: CY/ GVAX/ CRS-207/ nivolumabCRS-207-
Arm A: CY/ GVAX/ CRS-207/ nivolumabnivolumab-
Arm A: CY/ GVAX/ CRS-207/ nivolumabCY-
Arm B: CY/ GVAX/ CRS-207CRS-207-
Arm B: CY/ GVAX/ CRS-207GVAX-
Arm A: CY/ GVAX/ CRS-207/ nivolumabGVAX-
Arm B: CY/ GVAX/ CRS-207CY-
Primary Outcome Measures
NameTimeMethod
Overall Survival (OS)2 years and 7 months

OS will be measured from date of randomization until death or end of followup (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis).

Secondary Outcome Measures
NameTimeMethod
Tumor Marker Kinetics (CA 19-9) in Patients With Baseline Abnormal Levels as Measured by Number of Participants With Stable or Responding CA19-9 Concentration120 days

Number of participants with stable or responding (\<50% increase of serum CA19-9 concentration) at 120 days.

Immune-related Progression-free Survival (irPFS) by IRRC in Metastatic Pancreatic Cancer Patients2 years and 7 months

irPFS is defined as the number of months from the date of randomization to disease progression (PD or relapse from CR as assessed using irRC RECIST 1.1 criteria) or death due to any cause. Per irRC criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in tumor burden compared with baseline, Progressive Disease (PD) is \>20% increase in tumor burden compared with nadir, Stable Disease (SD) is \<30% decrease in tumor burden compared with baseline or \<20% increase in tumor burden compared to nadir.

Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity2 years and 7 months

When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.

Progression-free Survival (PFS) in Metastatic Pancreatic Cancer Patients2 years and 7 months

PFS is defined as the number of months from the date of randomization to disease progression (progressive disease \[PD\] or relapse from complete response \[CR\] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.

Time to Progression (TTP) by RECIST 1.1 in Metastatic Pancreatic Cancer Patients2 years and 7 months

Time to progression (TTP) is defined as the time from randomization to the date of documented disease progression as defined by RECIST 1.1 criteria. Individuals are censored at the date of the last radiological assessment that occurs prior to any of the following: death, switch to another anti-cancer therapy, or end of follow-up. Individuals without follow-up or baseline measurements are censored at 1 day. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.

Number of Participants With Partial Response (PR) or Complete Response (CR) as Defined by RECIST 1.1 in Metastatic Pancreatic Cancer Patients2 years and 7 months

Per RECIST 1.1 criteria, PR is defined as =\>30% decrease in sum of diameters of target lesions and CR is the disappearance of all target lesions.

Trial Locations

Locations (5)

University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

Stanford University

🇺🇸

Stanford, California, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

🇺🇸

Baltimore, Maryland, United States

Providence Portland Medical Center

🇺🇸

Portland, Oregon, United States

University of California, San Francisco

🇺🇸

San Francisco, California, United States

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