PROSTVAC in Combination With Nivolumab in Men With Prostate Cancer

Prostate Cancer Clinical Trial

Official title: Phase I/II Study of PROSTVAC in Combination With Nivolumab in Men With Prostate Cancer

Status Completed

Clinical Trial Summary

Background:

The immune system is the cells and organs in the body that recognize and fight infection and cancer. The prostate specific antigen (PSA)/TRICOM (PROSTVAC) vaccine might teach the immune system to find and kill certain prostate cancer cells. Nivolumab is a drug that allows the immune system to fight tumors. It might help PROSTVAC work better.

Objective:

To test the safety and effectiveness of the combination of PROSTVAC and nivolumab. To test this for people with castration resistant prostate cancer and then for other people with localized prostate cancer who are candidates for surgical removal of the prostate.

Eligibility:

Men ages 18 and older with prostate cancer

Design:

Participants will be screened with:

Medical history

Physical exam

Blood and urine tests

Electrocardiogram

Bone scan

Computed tomography (CT) scan or magnetic resonance imaging (MRI)

Tumor sample. This may be from a previous procedure.

All participants will get a combination of the study drugs over 8 weeks. They will have 1 visit for the initial injection then 3 booster injection / nivolumab infusion visits. Blood will be tested at these visits.

Over the next 4 weeks, some participants will have:

An exam of the large intestine through the rectum.

CT and bone scans

Standard hormonal treatment

Option to continue treatment every 3 weeks if their disease does not get worse. They will have scans every 12 weeks.

Other participants will have surgery to remove the prostate in week 9.

Participants will have a safety visit about a month after their last treatment. This will include a physical exam, blood tests, and possibly scans.

If their cancer progresses, participants will leave the study and may enroll in a long-term follow-up study. They will be contacted once a year to ask about their cancer and treatment.

Clinical Trial Description

Background:

Immune checkpoint inhibitors interfere with the immune systems autoregulatory mechanisms, allowing for a potentially expanded and prolonged T-cell response with the possibility of greater antitumor effects.

Nivolumab is a fully human Immunoglobulin G4 (IgG4) monoclonal antibody that targets the programmed cell death protein 1 (PD-1) protein. Specifically, the antibody binds to the PD-1 receptor and blocks its interaction with programmed death-ligand 1 (PD-L1) and programmed cell death 1 ligand 2 (PD-L2), thereby releasing PD-1 pathway-mediated inhibition of the immune response, including anti-tumor immune response.

PROSTVAC (developed by the National Cancer Institute [NCI] and licensed to Bavarian Nordic Immunotherapeutics, Mountain View, California (CA) is a therapeutic cancer vaccine for prostate cancer. Early studies have demonstrated immunologic efficacy and suggested clinical benefit. A phase III trial has completed accrual.

A previous study combining the immune checkpoint inhibitor ipilimumab and PROSTVAC suggested greater efficacy than PROSTVAC alone. Additional studies have demonstrated the potential efficacy of immunologic combination therapy with the immune checkpoint inhibitor nivolumab.

This study will aim to evaluate the impact of the combination of PROSTVAC and the immune checkpoint inhibitor nivolumab on the tumor microenvironment focusing on immune cell infiltration as the primary endpoint.

United States (US)-MRI imaging technology will be employed to sample the tumor before treatment and after radical prostatectomy.

The findings from this study could serve as the basis for future studies with this combination in this population of participants and more advanced disease.

Objectives:

Safety (For castration resistant prostate cancer (CRPC) lead-in cohort)

Evaluate changes in T-cell infiltration in the tumor after neoadjuvant treatment with PROSTVAC and nivolumab, relative to changes seen in a phase 2 trial with PROSTVAC alone in the neoadjuvant setting- NCT02153918 (For the neoadjuvant cohort).

Eligibility:

Participants must have histopathological documentation of adenocarcinoma of the prostate prior to starting this study and evaluable biopsy tissue (e.g., unstained slides or blocks) available for analysis.

For the castration resistant lead in cohort, if histopathological documentation is unavailable, a rising prostate specific antigen (PSA) and a clinical course consistent with prostate cancer would be acceptable.

Participants must have a performance status of 0 to 1 according to the Eastern Cooperative Oncology Group (ECOG) criteria.

Hematological eligibility parameters (within 16 days of starting therapy):

Granulocyte count 1,500/mm^3

Platelet count 100,000/mm^3

Hemoglobin (Hgb) >= 8 g/dL

Biochemical eligibility parameters (within 16 days of starting therapy):

Hepatic function: Bilirubin < 1.5 mg/dl (OR in participants with Gilbert's syndrome, total bilirubin <= 3.0 mg/dL), aspartate aminotransferase (AST) and alanine transaminase (ALT) <= 2.5 times upper limit of normal.

Creatinine <= 1.5 X ULN

Design:

The primary focus of this study will be to evaluate PROSTVAC and nivolumab in the neoadjuvant setting.

Lead-in cohort evaluating the safety and tolerability of this combination in the castration resistant setting (CRPC cohort)

Following this lead-in cohort in the CRPC setting, we will enroll a cohort in the neoadjuvant setting evaluating the combination of PROSTVAC and nivolumab.

The lead-in safety cohort will require 10 participants and the neoadjuvant cohort will require 17 evaluable participants. In order to allow for a small number of inevaluable participants, the accrual ceiling will be set to 29 participants. ;

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

• NCT number: NCT02933255
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 18, 2017
• Completion date: December 1, 2023