Immunotherapy + Chemotherapy for Metastatic Colorectal Cancer
Trial Summary
What is the purpose of this trial?
This is a multi-center Phase II randomized study. We plan to enroll 78 patients with biopsy-proven hepatic-limited metastatic colorectal cancer deemed resectable after multi-disciplinary discussion. Eligible patients must have confirmed isolated liver metastases by radiographic imaging of the investigators' choosing. Imaging must include the chest, abdomen, and pelvis regardless of imaging modality chosen. Patients will be randomized to either the control arm or the experimental arm. The control arm will receive mFOLFOX6 every 2 weeks for 4 cycles concurrently with Nivolumab. The experimental arm will first be treated with 2 vaccinations of MVA-BN-CV301 given two weeks apart (Days -28, -14) concurrently with Nivolumab followed by 4 vaccinations of FPV-CV301 given two weeks apart concurrently with mFOLFOX6 and Nivolumab, which will again be administered every 2 weeks for 4 cycles (FPV-CV301, mFOLFOX6 and Nivolumab) After Cycle 4, patients will be re-evaluated for surgical resection by re-staging CT chest, abdomen and pelvis (C/A/P). Patients still considered resectable will undergo surgical resection with the goal of complete resection. Patients who cannot be completely resected will continue to be followed on study, and an additional appropriate candidate will be randomized to the corresponding arm.We will collect peripheral blood and tumor tissue at the time of surgical resection, if applicable, or by re-biopsy if resection is not possible. Post-operative therapy will begin when patients are deemed ready by their surgical oncologist team. Patients in the control arm will then undergo another 8 cycles of mFOLFOX6 with Nivolumab administered concurrently. Nivolumab will then be administered every four weeks. The experimental arm will receive the same post-operative regimen but including FPV-CV301 boosters given concurrently with mFOLFOX6 and Nivolumab. FPV-CV301 will then be administered every 12 weeks, and Nivolumab every 4 weeks. We will collect peripheral blood for evaluation of correlates upon the completion of therapy. The vaccination approach of initial immunization during the neoadjuvant period followed by FPV-CV301 boosters for two years postoperatively was chosen to optimize the induction of a long-lasting tumor-specific host response. Neoadjuvant vaccination will also allow for analysis of the tumor microenvironment in resection specimens.Post-therapy patients will be under surveillance per NCCN guidelines with repeat CEA every 3 months for 2 years followed by every 6 months for 1 year (total 3 years), repeat CT of the C/A/P every 3 months for 2 years followed by every 6 months for up to 1 year (total 3 years), and colonoscopy at one year with repetition based on findings at the time of the procedure.
Research Team
Patrick Boland, M.D.
Principal Investigator
Rutgers Cancer Institute of New Jersey
Eligibility Criteria
This trial is for adults with colorectal cancer that has spread to the liver but can be surgically removed. They must not have had previous treatment for stage IV cancer, though past oxaliplatin therapy is okay if over a year ago. Participants need proper kidney and liver function, no serious allergies or autoimmune diseases, and women of childbearing age must test negative for pregnancy.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Neoadjuvant Treatment
Participants receive either mFOLFOX6 and Nivolumab or MVA-BN-CV301 vaccinations with Nivolumab followed by FPV-CV301, mFOLFOX6, and Nivolumab
Surgical Evaluation and Resection
Patients are re-evaluated for surgical resection and undergo surgery if resectable
Post-operative Treatment
Post-operative therapy with mFOLFOX6 and Nivolumab, with FPV-CV301 boosters in the experimental arm
Follow-up
Participants are monitored for safety and effectiveness after treatment, with surveillance per NCCN guidelines
Treatment Details
Interventions
- FPV-CV301
- mFOLFOX6
- MVA-BN-CV301
- Nivolumab
Find a Clinic Near You
Who Is Running the Clinical Trial?
Kristen Spencer
Lead Sponsor
Patrick Boland
Lead Sponsor
Hoosier Cancer Research Network
Collaborator
Bristol-Myers Squibb
Industry Sponsor
Christopher Boerner
Bristol-Myers Squibb
Chief Executive Officer since 2023
PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis
Deepak L. Bhatt
Bristol-Myers Squibb
Chief Medical Officer since 2024
MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania
Bavarian Nordic
Industry Sponsor
Paul Chaplin
Bavarian Nordic
Chief Executive Officer since 2014
PhD in Immunology from Bristol University
Jean-Christophe May
Bavarian Nordic
Chief Medical Officer since 2020
PharmD and MBA