Study of CRS-207, Nivolumab, and Ipilimumab With or Without GVAX Pancreas Vaccine (With Cy) in Patients With Pancreatic Cancer

August 5, 2024 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

A Randomized Phase 2 Study of the Safety, Efficacy, and Immune Response of CRS-207, Nivolumab, and Ipilimumab With or Without GVAX Pancreas Vaccine (With Cyclophosphamide) in Patients With Previously Treated Metastatic Pancreatic Adenocarcinoma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

61

Phase

  • Phase 2

Contacts and Locations

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

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • Johns Hopkins SKCCC

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: CY, Nivolumab, Ipilimumab, GVAX, CRS-207
Drug: Cyclophosphamide
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.
Other Names:
  • CY
Drug: Nivolumab
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.
Other Names:
  • anti-PD-1, OPDIVO
Drug: Ipilimumab
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.
Other Names:
  • YERVOY®
Drug: GVAX Pancreas Vaccine
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.
Other Names:
  • GVAX, PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1/GM-Neo vaccine
Drug: CRS-207
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.
Drug: CRS-207
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.
Experimental: Arm B: Nivolumab, Ipilimumab, CRS-207
Drug: Nivolumab
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.
Other Names:
  • anti-PD-1, OPDIVO
Drug: Ipilimumab
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.
Other Names:
  • YERVOY®
Drug: CRS-207
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.
Drug: CRS-207
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1)
Time Frame: 18 months
Objective Response Rate (ORR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions. Participants who discontinue due to toxicity or clinical progression prior to post-baseline tumor assessments will be considered as non-responders. Participants who discontinue for other reasons prior to their first dose of study drug will not included in the analysis.
18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Experiencing Grade 3 or Above Study Drug-related Adverse Events (AEs)
Time Frame: 21 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. Laboratory abnormalities that were asymptomatic and not clinically significant were excluded.
21 months

Collaborators and Investigators

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

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

Bristol-Myers Squibb
National Cancer Institute (NCI)
Aduro Biotech, Inc.

Investigators

  • Principal Investigator: Dung Le, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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 Major Dates

Study Start (Actual)

December 14, 2017

Primary Completion (Actual)

August 3, 2022

Study Completion (Actual)

August 23, 2023

Study Registration Dates

First Submitted

June 15, 2017

First Submitted That Met QC Criteria

June 15, 2017

First Posted (Actual)

June 16, 2017

Study Record Updates

Last Update Posted (Actual)

August 7, 2024

Last Update Submitted That Met QC Criteria

August 5, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • J1790
  • 5P01CA247886-02 (U.S. NIH Grant/Contract)
  • IRB00137389 (Other Identifier: Johns Hopkins University)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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