Nivolumab in Patients With High-Risk Biochemically Recurrent Prostate Cancer

A Phase 2 Study of Nivolumab in Patients With High-Risk Biochemically Recurrent Prostate Cancer

This research study is studying an immune-based cancer drug as a possible treatment for prostate cancer.

The drug involved in this study is:

-Nivolumab

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Nivolumab

Detailed Description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved nivolumab for this specific disease but it has been approved for other uses. Nivolumab is an antibody inhibitor of the programmed death-1 (PD-1) pathway. By blocking PD-1, this medication may allow the immune system to recognize and fight cancer.

In this research study, the investigators are investigating whether nivolumab has any activity in patients who have a rising PSA (prostate specific antigen) after previously undergoing surgery or radiation for prostate cancer. Although nivolumab was previously not found to have significant effect in advanced prostate cancer after all other therapies had failed, based on new research, the investigators are testing whether nivolumab could have a greater effect earlier in the disease course and before patients receive hormone therapies.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02135
      • St. Elizabeth's Medical Center
    • South Weymouth, Massachusetts, United States, 02190
      • DFCI South Shore
  • New Hampshire
    • Londonderry, New Hampshire, United States, 03053
      • DFCI Londonderry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have signed an informed-consent form indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study.
• Patients must have a history of prostate adenocarcinoma (adenocarcinoma must be the primary histology; secondary components of variant histologies are acceptable) confirmed on biopsy and treated with primary radical prostatectomy (RP) or definitive radiation (RT). Prior salvage RT is acceptable.

• Patients must have experienced biochemical recurrence (BCR) plus have minimum PSA values noted below:

  • Following primary RP: Any detectable rising PSA after RP (or after salvage RT if performed), minimum PSA 1.0 at time of screening
  • Following primary RT: PSA rise to ≥2 ng/mL above the nadir
  • No evidence of metastases on conventional imaging (CT or MRI plus bone scan)
• PSA doubling time (PSADT) <10 months --PSADT: calculated as per Prostate Cancer Working Group 3 (PCWG3) and the Memorial Sloan Kettering Cancer Center calculator: (https://www.mskcc.org/nomograms/prostate/psa_doubling_time)

With linear regression model of normal logarithm of PSA and time, based on:

• At least 3 consecutive PSA values with each value ≥0.2 ng/mL

• Interval between first and last PSA values is ≥8 weeks but ≤12 months.

  -Archival tissue is mandatory, either prostatectomy specimen or (in patients who received primary RT) diagnostic core biopsies. Patients must consent to next-generation sequencing performed on this tissue.

• If diagnostic core biopsies are only available tissue, at least 3 cores must be involved by tumor

  • Easteron Cooperative Oncology Group (ECOG) performance status 0-1
  • Age ≥18 years
  • Adequate organ and marrow function:
  • System Laboratory Value
• Hematological
• White blood cell (WBC) ≥ 2000/µL
• Absolute Neutrophil Count (ANC) ≥ 1500/μL
• Platelets (Plt) ≥ 100 x103/μL

• Hemoglobin (Hgb) > 9.0 g/dL (with or without transfusion)

  -Renal

• Serum Creatinine ≤ 2 x ULN
• Hepatic
• Bilirubin1 ≤ 1.5× upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 3 × ULN

• Alanine aminotransferase (ALT) ≤ 3 × ULN

  • Except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL
  • Baseline testosterone ≥100 ng/dL
  • Recovery from acute toxicity related to prior therapy, including surgery and radiation, or no treatment-related toxicity ≥ grade 2.
  • History of prior malignancy or concurrent separate malignancy is not an exclusion criterion so long as the non-prostate malignancy is stable and does not require any treatment.
  • Able to understand and sign informed consent and adhere to study procedures.
  • Male patients whose female partners are of reproductive potential must agree to use a contraception during the trial period

Exclusion Criteria:

• Current use of ADT or plan to initiate ADT during trial period
• Major surgery or radiation therapy within 14 days of starting study treatment
• Subjects with active autoimmune disease. Patients with a history of autoimmune disease that has not required systemic immunosuppressive therapy or does not threaten vital organ function including central nervous system, heart, lungs, kidneys, skin, and gastrointestinal tract will be allowed.
• Known history of immune deficiencies or chronic viral infections including HIV, hepatitis B (HBV), and hepatitis C (HCV) (patients with prior therapy for HBV or HCV is permitted if viral clearance was documented).
• Concurrent medical condition requiring use of systemic corticosteroids with prednisone >10 mg per day or equivalent. Use of inhaled, nasal, and topical steroids (applied to small body areas) is allowed.
• Current use (within past 4 weeks) of other prohibited medications including anti-cancer therapies, hormonal therapies, 5-alpha reductase inhibitors, and alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto).
• Prior treatment with immune checkpoint inhibitors. (Prior cancer vaccines are allowed.)
• Serious intercurrent medical or psychiatric illness that, in the judgment of the investigator, would interfere with patient's ability to carry out the treatment program

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PD-L1 Positive; -Nivolumab will be given on day 1 of a 28-day cycle intravenously	Drug: Nivolumab; Nivolumab is an antibody inhibitor of the programmed death-1 (PD-1) pathway. By blocking PD-1, this medication may allow the immune system to recognize and fight cancer; Other Names: Opdivo
Experimental: PD-L1 Negative; -Nivolumab will be given on day 1 of a 28-day cycle intravenously	Drug: Nivolumab; Nivolumab is an antibody inhibitor of the programmed death-1 (PD-1) pathway. By blocking PD-1, this medication may allow the immune system to recognize and fight cancer; Other Names: Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate at 12 Weeks	Proportion of patients with high-risk biochemically-recurrent (BCR) prostate cancer (PCa) who achieve disease control at 12 weeks, defined as a decline or stabilization in prostate-specific antigen (PSA) levels without symptomatic or radiographic progression, following 12 weeks of nivolumab treatment.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Maximal Change in Prostate Specific Antigen (PSA) During Nivolumab Treatment	Maximum percent change in prostate-specific antigen (PSA) from baseline observed at any time during nivolumab treatment, defined as the greatest decrease or increase in PSA relative to baseline. Participants are categorized based on maximum percent change in PSA as <10% or ≥10% change.	2 years
Change in PSA Doubling Time (PSADT) Prior to End of Treatment Relative to Baseline	Pre-treatment PSA doubling time (PSADT) was calculated using at least three PSA values obtained prior to treatment initiation. On-treatment PSADT required three consecutive PSA values ≥ 0.2 ng/mL, with the first and last measurements occurring within 12 months. End-of-treatment (EOT) PSADT was calculated using the three PSAs obtained immediately prior to EOT; it was not calculated for patients who discontinued treatment before cycle 4. PSADT was estimated using a linear regression model of the natural logarithm of PSA over time, following PCWG3 recommendations and the MSKCC calculator.	2 years
Median Time to Radiographic Progression to Metastatic Disease	Time to radiographic progression to metastatic disease was defined as the interval from treatment initiation to the first documentation of radiographic disease progression to metastatic disease per RECIST v1.1 criteria and Prostate Cancer Working Group (PCWG) guidelines, or censored at the date of last imaging assessment.	From initiation of nivolumab treatment until the date of first documented disease progression, assessed up to the end of the study.
Median Time to Initiation of Androgen Deprivation Therapy (ADT) After Nivolumab	Time to initiation of ADT was defined as the interval from initiation of nivolumab to the start of systemic ADT. Participants who did not initiate ADT were censored at the date of last follow-up.	From the first dose of nivolumab to initiation of ADT, assessed through end of study follow-up.
Number of Participants With Treatment Related Grade ≥3 Adverse Events	The number of participants experiencing treatment-related adverse events of Grade 3 or higher that were assessed as definitely or probably related to study treatment, graded according to CTCAE v5.0.	2 years

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: Bristol-Myers Squibb; Dana-Farber Cancer Institute
• Investigators: Principal Investigator: David J. Einstein, MD, Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2018
• Primary Completion (Actual): September 30, 2023
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 16, 2018
• First Submitted That Met QC Criteria: August 16, 2018
• First Posted (Actual): August 20, 2018

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Prostate Cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab
• Other Study ID Numbers: 18-249

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No