Neoantigen DNA Vaccine in Combination With Nivolumab/Ipilimumab and PROSTVAC in Metastatic Hormone-Sensitive Prostate Cancer

Part of paid clinical trials in St Louis, Missouri.

Sponsor
Washington University School of Medicine
Study ID
NCT03532217
Phase
PHASE1
Status
Completed

Conditions

  • Metastatic Hormone-Sensitive Prostate Cancer

Eligibility Criteria

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

Interventions

  • PROSTVAC-V — BIOLOGICAL
    -Replication-competent vaccinia virus which has been engineered to encode the sequences for a modified human prostate-specific antigen (PSA) and a triad of co-stimulatory molecules (TRICOM)
  • PROSTVAC-F — BIOLOGICAL
    -Fowlpox virus which does not replicate in human cells and has been engineered to encode the same sequences present in PROSTVAC-V.
  • Nivolumab — DRUG
    -Nivolumab is a human monoclonal antibody (mAb)
  • Ipilimumab — DRUG
    -Ipilimumab is a mAb blocking the inhibitory signal mediated by cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4), a protein receptor that downregulates the immune system.
  • Neoantigen DNA vaccine — BIOLOGICAL
    Each DNA vaccination will be 1 mL vaccine administered intramuscularly. At each vaccination time point, patients will receive two injections at separate sites.
  • TriGrid Delivery System — DEVICE
    -Electroporation device
  • Tumor biopsy — PROCEDURE
    -Pre-treatment, post-treatment A (optional), and end of treatment
  • Peripheral blood — PROCEDURE
    -At the time of pre-treatment biopsy, mid-treatment of chemo-ADT, at time of enrollment (prior to POSTVAC administration), mid-treatment A, mid-treatment B (multiple)
  • Fecal samples — PROCEDURE
    -Post chemo/pre-treatment A, post-treatment A, pre-treatment B, post-treatment B
  • Leukapheresis — PROCEDURE
    * Post-treatment A/pre-treatment B * Mid-Treatment B, after Cycle 9 Day 1 and prior to Cycle 10 Day 1 * End of treatment

Study Details

This study study aims to elucidate the immune responses to a shared antigen vaccine (PROSTVAC) and tumor specific antigens generated DNA vaccine in combination with checkpoint blockade using nivolumab (anti-PD-1), and ipilimumab (anti-CTLA-4). Additionally, the investigators will study the impact of the combination immunotherapy on peripheral T cell activation, as well as immune response in the tumor microenvironment. Finally, the investigators will evaluate the safety and tolerability to this novel personalized immunotherapy in combination with checkpoint blockade.

Key Dates

Start date
Sep 14, 2018
Status verified
Aug 2022
Primary completion
Apr 1, 2022
Completion
Jul 25, 2022

Study Design

Enrollment
19 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: PROSTVAC/Ipilimumab/Nivolumab/Neoantigen DNA vaccine
    * Within 60 days after the last chemo, patients will start a priming dose of PROSTVAC-V, and subsequent doses of PROSTVAC- F (weeks 0, 2, 5, 8, 11, 14, and 17). During "Treatment A" phase, subjects should receive nivolumab intravenously on Day 1 of each cycle every 3 weeks for 6 doses. Ipilimumab on Day 1 of each cycle every 3 weeks for 2 doses. * Patients will then receive a neoantigen DNA vaccine with continuous nivolumab treatment. The vaccine will be administered starting approximately week 21 by intramuscular injection for a total of 6 treatments every 28 days +/-7 days. Each DNA vaccination will be 4 mg vaccine administered intramuscularly using a TriGrid electroporation device. Patients will receive nivolumab at 480 mg every 28 days concurrently with neoantigen DNA vaccine. This is Treatment B. In the event the DNA vaccine production is delayed, patients will receive single agent nivolumab every 4 weeks beginning week 21 until the vaccine is ready

Primary Outcome Measure

Safety and tolerability of regimen as defined by incidence of adverse events [ Time Frame: Through 100 days after completion of treatment (estimated to be 55 weeks) ]

Locations (1)

FacilityCityStateZIPSite coordinators
Washington University School of MedicineSt LouisMissouri63110-

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By research site
Washington University School of Medicine· St Louis, MO

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