A Trial of Perioperative CV301 Vaccination in Combination With Nivolumab and Systemic Chemotherapy for Metastatic CRC

Part of paid clinical trials in Duarte, California.

Sponsor
Patrick Boland
Study ID
NCT03547999
Phase
PHASE2
Status
Terminated

Conditions

  • Metastatic Colorectal Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • mFOLFOX6 — DRUG
    The control arm (Arm A) and experimental arm (Arm B) will receive mFOLFOX6 every 2 weeks for 4 cycles. Once patients in the post-operative period are deemed ready to begin therapy, patients in the control arm will then undergo another 8 cycles of mFOLFOX6.
  • MVA-BN-CV301 — BIOLOGICAL
    The experimental arm (Arm B) will receive MVA-BN-CV301 in 4 injections of 4 x 10(8) infectious units/0.5 mL given subcutaneously prior to the start of chemotherapy on days -28 and -14.
  • FPV-CV301 — BIOLOGICAL
    The experimental arm (Arm B) will receive FPV-CV301 in 1 dose of 1 x 10(9) infectious units/0.5 mL given subcutaneously concurrently with chemotherapy (at least an hour prior to chemotherapy) on days 0, 14, 28 and 42 pre-operatively, and FVP-CV301 boosters on day 0 and 14 and then every 4 weeks (day 42, 70, 98). After day 98, FVP-CV301 will then be administered every twelve weeks completing therapy at week 110.
  • Nivolumab — DRUG
    Nivolumab at a dose of 240 mg as a 30 minute IV infusion every 2 weeks until progression. Arm B will receive Nivolumab starting with the vaccinations. Arm A will begin the Nivolumab with the initiation mFOLFOX.

Study Details

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.

Key Dates

Start date
Jun 26, 2018
Status verified
Jul 2025
Primary completion
Mar 13, 2024
Completion
Mar 13, 2024

Study Design

Enrollment
17 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Arm A - Control
    mFOLFOX6 and Nivolumab every 2 weeks for 4 cycles. After neoadjuvant therapy, patients will be re-evaluated for surgical resection. Patients still considered resectable will undergo surgical resection with the goal of completely treating all of their disease by either resection and/or ablation. Patients with bilobar disease must have all of their disease treated in a single operation. Once patients in the post-operative period are deemed ready to begin therapy, patients in the control arm will then undergo another 8 cycles of mFOLFOX6 in addition to Nivolumab. After this, Nivolumab will be given every 4 weeks completing therapy at week 110.
  • Experimental: Arm B - Experimental
    Two doses of Nivolumab and MVA-BN-CV301 each given 2 weeks apart (Days -28, -14), followed by four doses of Nivolumab plus FPV-CV301 given 2 weeks apart concurrently with mFOLFOX6, which will again be administered every 2 weeks for 4 cycles (Nivolumab, FPV-CV301 and mFOLFOX6). After neoadjuvant therapy, patients will be re-evaluated for surgical resection. Patients still considered resectable will undergo surgical resection with the goal of completely treating all of their disease by either resection and/or ablation. Patients with bilobar disease must have all of their disease treated in a single operation. Patients in the experimental arm will receive 8 cycles of mFOLFOX6 in addition to Nivolumab and FVP-CV301 boosters with the first two given on Day 0 and 14 and then every 4 weeks. FVP-CV301 will then be administered every twelve weeks completing therapy at week 110.

Primary Outcome Measure

3-year Overall Survival (OS) Rate From Metastasectomy [ Time Frame: 3 years ]

Locations (7)

FacilityCityStateZIPSite coordinators
City of HopeDuarteCalifornia91010-
University of MiamiMiamiFlorida33136-
University of Kansas Medical Center Research Institute, Inc.WestwoodKansas66205-
Rutgers Cancer Institute of New JerseyNew BrunswickNew Jersey08903-
Cleveland ClinicClevelandOhio44195-
Ohio State University Comprehensive Cancer CenterColumbusOhio43210-
Oregon Health & Science UniversityPortlandOregon97239-

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