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Nivolumab in Patients With High-Risk Biochemically Recurrent Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03637543
Recruitment Status : Recruiting
First Posted : August 20, 2018
Last Update Posted : September 22, 2020
Bristol-Myers Squibb
Information provided by (Responsible Party):
David J. Einstein, MD, Beth Israel Deaconess Medical Center

Tracking Information
First Submitted Date  ICMJE August 16, 2018
First Posted Date  ICMJE August 20, 2018
Last Update Posted Date September 22, 2020
Actual Study Start Date  ICMJE October 18, 2018
Estimated Primary Completion Date March 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 16, 2018)
Disease Control [ Time Frame: 12 weeks ]
Proportion of patients with high-risk biochemically-recurrent (BCR) prostate cancer (PCa) that experiences decline or stabilization in PSA (without symptomatic/radiographic progression) after 12 weeks of nivolumab treatment
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 16, 2018)
  • Maximal change in prostate specific antigen (PSA) during nivolumab treatment [ Time Frame: 2 years ]
  • Best PSA response during nivolumab treatment as an absolute change relative to baseline [ Time Frame: 2 years ]
  • Change in PSA doubling time (PSADT) at end-of-study relative to baseline [ Time Frame: 2 years ]
  • Time from enrollment to development of radiographic metastatic disease [ Time Frame: 2 years ]
  • Time from enrollment to initiation of androgen deprivation therapy (ADT) [ Time Frame: 2 years ]
  • Treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Nivolumab in Patients With High-Risk Biochemically Recurrent Prostate Cancer
Official Title  ICMJE A Phase 2 Study of Nivolumab in Patients With High-Risk Biochemically Recurrent Prostate Cancer
Brief Summary

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

The drug involved in this study is:


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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE 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 Name: Opdivo
Study Arms  ICMJE
  • Experimental: PD-L1 Positive
    -Nivolumab will be given on day 1 of a 28-day cycle intravenously
    Intervention: Drug: Nivolumab
  • Experimental: PD-L1 Negative
    -Nivolumab will be given on day 1 of a 28-day cycle intravenously
    Intervention: Drug: Nivolumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 16, 2018)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2025
Estimated Primary Completion Date March 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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: (

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)


  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: David J. Einstein, MD 617-667-2100
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03637543
Other Study ID Numbers  ICMJE 18-249
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party David J. Einstein, MD, Beth Israel Deaconess Medical Center
Study Sponsor  ICMJE Beth Israel Deaconess Medical Center
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: David J. Einstein, MD Beth Israel Deaconess Medical Center
PRS Account Dana-Farber Cancer Institute
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP