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

Primary Purpose

Previously Treated Metastatic Adenocarcinoma of the Pancreas

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CRS-207
CRS-207
nivolumab
GVAX
CY
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Previously Treated Metastatic Adenocarcinoma of the Pancreas

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California, San Francisco
  • Stanford University
  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Providence Portland Medical Center
  • University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A: CY/ GVAX/ CRS-207/ nivolumab

Arm B: CY/ GVAX/ CRS-207

Arm Description

Outcomes

Primary Outcome Measures

Overall Survival (OS)
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

Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity
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 Patients
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.
Immune-related Progression-free Survival (irPFS) by IRRC in Metastatic Pancreatic Cancer Patients
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.
Time to Progression (TTP) by RECIST 1.1 in Metastatic Pancreatic Cancer Patients
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 Patients
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.
Tumor Marker Kinetics (CA 19-9) in Patients With Baseline Abnormal Levels as Measured by Number of Participants With Stable or Responding CA19-9 Concentration
Number of participants with stable or responding (<50% increase of serum CA19-9 concentration) at 120 days.

Full Information

First Posted
September 15, 2014
Last Updated
March 17, 2021
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
Bristol-Myers Squibb, Stand Up To Cancer, Aduro Biotech, Inc., American Association for Cancer Research, Lustgarten Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT02243371
Brief Title
GVAX Pancreas Vaccine (With CY) and CRS-207 With or Without Nivolumab
Official Title
A Randomized Phase 2 Study of the Safety, Efficacy, and Immune Response of GVAX Pancreas Vaccine (With Cyclophosphamide) and CRS-207 With or Without Nivolumab in Patients With Previously Treated Metastatic Pancreatic Adenocarcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
January 2, 2015 (Actual)
Primary Completion Date
July 21, 2017 (Actual)
Study Completion Date
July 21, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
Bristol-Myers Squibb, Stand Up To Cancer, Aduro Biotech, Inc., American Association for Cancer Research, Lustgarten Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Previously Treated Metastatic Adenocarcinoma of the Pancreas

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
93 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A: CY/ GVAX/ CRS-207/ nivolumab
Arm Type
Experimental
Arm Title
Arm B: CY/ GVAX/ CRS-207
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
CRS-207
Intervention Description
1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6
Intervention Type
Biological
Intervention Name(s)
CRS-207
Intervention Description
1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6
Intervention Type
Drug
Intervention Name(s)
nivolumab
Other Intervention Name(s)
BMS-936558; anti-PD-1 mAb
Intervention Description
3 mg/kg administered IV on Day 1 of Cycles 1-6
Intervention Type
Biological
Intervention Name(s)
GVAX
Other Intervention Name(s)
GVAX pancreas vaccine, Panc 10.05 pcDNA-1/GM-Neo, Panc 6.03 pcDNA-1/GM-Neo
Intervention Description
5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2
Intervention Type
Drug
Intervention Name(s)
CY
Other Intervention Name(s)
Cytoxan, Cyclophosphamide
Intervention Description
200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
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).
Time Frame
2 years and 7 months
Secondary Outcome Measure Information:
Title
Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity
Description
When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.
Time Frame
2 years and 7 months
Title
Progression-free Survival (PFS) in Metastatic Pancreatic Cancer Patients
Description
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 Frame
2 years and 7 months
Title
Immune-related Progression-free Survival (irPFS) by IRRC in Metastatic Pancreatic Cancer Patients
Description
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.
Time Frame
2 years and 7 months
Title
Time to Progression (TTP) by RECIST 1.1 in Metastatic Pancreatic Cancer Patients
Description
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.
Time Frame
2 years and 7 months
Title
Number of Participants With Partial Response (PR) or Complete Response (CR) as Defined by RECIST 1.1 in Metastatic Pancreatic Cancer Patients
Description
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.
Time Frame
2 years and 7 months
Title
Tumor Marker Kinetics (CA 19-9) in Patients With Baseline Abnormal Levels as Measured by Number of Participants With Stable or Responding CA19-9 Concentration
Description
Number of participants with stable or responding (<50% increase of serum CA19-9 concentration) at 120 days.
Time Frame
120 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dung Le, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Providence Portland Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
29997287
Citation
Hopkins AC, Yarchoan M, Durham JN, Yusko EC, Rytlewski JA, Robins HS, Laheru DA, Le DT, Lutz ER, Jaffee EM. T cell receptor repertoire features associated with survival in immunotherapy-treated pancreatic ductal adenocarcinoma. JCI Insight. 2018 Jul 12;3(13):e122092. doi: 10.1172/jci.insight.122092.
Results Reference
derived

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

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