GVAX Pancreas Vaccine (With CY) And CRS-207 With Or Without Nivolumab

Study Overview

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

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).

N/A

Previously Treated Metastatic Adenocarcinoma of the Pancreas

BIOLOGICAL: CRS-207
BIOLOGICAL: CRS-207
DRUG: nivolumab
BIOLOGICAL: GVAX
DRUG: CY

J14113
ADU-CL-06
IRB00043936 (OTHER Identifier) (OTHER: JHMIRB)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2014-09-15	Results First Submitted 2019-08-06	Last Update Submitted that met QC Criteria 2021-03-17
First Submitted that Met QC Criteria 2014-09-16	Results First Submitted that Met QC Criteria 2019-09-16	Last Update Posted (ACTUAL) 2021-04-06
First Posted (ACTUAL) 2014-09-17	Results First Posted 2019-10-08	Last Verified 2020-02

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Arm A: CY/ GVAX/ CRS-207/ nivolumab	BIOLOGICAL: CRS-207 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6 DRUG: nivolumab 3 mg/kg administered IV on Day 1 of Cycles 1-6 BIOLOGICAL: GVAX 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 DRUG: CY 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2
EXPERIMENTAL: Arm B: CY/ GVAX/ CRS-207	BIOLOGICAL: CRS-207 1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6 BIOLOGICAL: GVAX 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2 DRUG: CY 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2

Participant Group/Arm

Intervention/Treatment

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

BIOLOGICAL: CRS-207

1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6

DRUG: nivolumab

3 mg/kg administered IV on Day 1 of Cycles 1-6

BIOLOGICAL: GVAX

5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2

DRUG: CY

200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2

EXPERIMENTAL: Arm B: CY/ GVAX/ CRS-207

BIOLOGICAL: CRS-207

1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6

BIOLOGICAL: GVAX

5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2

DRUG: CY

200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2

Primary Outcome Measures	Measure Description	Time Frame
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).	2 years and 7 months

Secondary Outcome Measures	Measure Description	Time Frame
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.	2 years and 7 months
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.	2 years and 7 months
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.	2 years and 7 months
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.	2 years and 7 months
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.	2 years and 7 months
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.	120 days

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Bristol-Myers Squibb
Stand Up To Cancer
Aduro Biotech, Inc.
American Association for Cancer Research
Lustgarten Foundation

Investigators

PRINCIPAL_INVESTIGATOR: Dung Le, MD, Johns Hopkins University

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.

Learn

Resources

Patients

Caregivers

Clinical Trial Record