We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

Combination of Nivolumab Immunotherapy With Radiation Therapy and Androgen Deprivation Therapy

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.
ClinicalTrials.gov Identifier: NCT03543189
Recruitment Status : Recruiting
First Posted : June 1, 2018
Last Update Posted : November 14, 2022
Bristol-Myers Squibb
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Brief Summary:
The purpose of this study is to test the safety, tolerability, and effectiveness of the investigational drug nivolumab (Opdivo™) in combination with high dose radiation. Investigators also want to see if these study drugs help to delay the progression of prostate cancer.

Condition or disease Intervention/treatment Phase
Prostate Cancer Prostate Disease Drug: Nivolumab Radiation: Brachytherapy Radiation: External Beam Radiation Therapy Drug: Androgen Deprivation Therapy Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Combination of Nivolumab Immunotherapy With Radiation Therapy and Androgen Deprivation Therapy in the Management of Gleason Group 5 Prostate Cancer
Actual Study Start Date : October 3, 2018
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Combination Therapy
Post androgen deprivation therapy (ADT), participants will receive nivolumab, HDR brachytherapy and external beam radiation therapy, followed by a 2 year follow-up period.
Drug: Nivolumab
Treatment with nivolumab will begin four weeks prior to the first brachytherapy treatment. Nivolumab will be given through a vein every 2 weeks for 4 courses. Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response, resulting in decreased tumor growth.
Other Name: Opdivo®

Radiation: Brachytherapy
High dose rate (HDR) Brachytherapy involves the delivery of a high dose of radiation, internally, directly to the prostate. This procedure is completed in one day as an outpatient procedure.
Other Name: HDR Brachytherapy

Radiation: External Beam Radiation Therapy
External beam radiation therapy to the participant's prostate will be given once a day, five days a week (Monday-Friday), for a total of five weeks. External radiation therapy treatments are given as an outpatient procedure and take about 10-15 minutes each day.
Other Names:
  • Radiotherapy
  • EBRT

Drug: Androgen Deprivation Therapy
Standard of care.
Other Name: ADT

Primary Outcome Measures :
  1. Phase 1: Safety Run In - Rate of Dose Limiting Toxicity (CTCAE V5.0) [ Time Frame: Up to 12 weeks after initiation of Nivolumab ]
    An initial set of 6 participants will be enrolled at Dose Level 1. If 0 or 1 dose limiting toxicity (DLT) is observed during Cycle 1, enrollment in the phase II at Dose Level 1 will be initiated. If DLT is observed in 2 patients during Cycle 1, an additional 3 participants will be enrolled at Dose Level 1 (total 9 patients). If DLT is observed in ≤ 2 of 9 patients, enrollment in the phase II as Dose Level 1 will be initiated. If DLT is observed in 3 or more of 9 patients at Dose Level 1, the maximum tolerated dose (MTD) will have been exceeded, this combination will be determined to be unsafe to conduct the phase II portion of the trial, and the trial will be discontinued. CTCAE

  2. Phase II: Relapse Free Survival Rate [ Time Frame: Up to 2 years ]
    PSA failure is defined for first line Radiotherapy (RT) treatment in accordance with NCCN guidelines: PSA failure for treatment with RT is defined as PSA increase by 2 ng/mL or more above the nadir PSA.

Secondary Outcome Measures :
  1. Time to PSA Nadir [ Time Frame: Up to 2 years ]
    To observe and record anti-tumor activity as defined by "time to PSA nadir". The PSA nadir is the absolute lowest level that the PSA drops after treatment.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Provision of signed and dated informed consent form.
  • Stated willingness to comply with all study procedures and availability for the duration of the study.
  • Male, aged ≥ 18 years
  • ECOG Performance Status: 0-1
  • Diagnosed with Grade Group 5 prostate cancer (PCa): Gleason grade 9 (4+5 or 5+4) or 10 (5+5) with >30% of cores involved; Any PSA or T-stage
  • Pathologically (histologically) proven diagnosis of PCa undergoing their first line of treatment
  • Biopsy specimen available
  • Patients with oligometastaic disease (defined as ≤3 sites of distant metastatic disease, and/or positive lymph nodes confined to the pelvis) being treated with curative intent are eligible for study participation
  • Eligible for definitive RT (HDR + EBRT) + short-term ADT
  • Undergoing radiation treatment at Moffitt Cancer Center
  • Participants being treated with nivolumab must have normal organ function as defined in protocol.
  • Males who are sexually active with women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug plus 5 half-lives of the study drug (half-life up to 25 days) plus 90 days (duration of sperm turnover) for a total of 31 weeks post-treatment completion; Azoospermic males are exempt from contraceptive requirements; Male participants must be willing to refrain from sperm donation during the entire study and for 5 half-lives of study drug plus 90 days (duration of sperm turnover).

Exclusion Criteria:

  • Autoimmune disease: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's Granulomatosis]) and motor neuropathy considered to be of autoimmune origin (e.g., Guillain-Barre Syndrome and Myasthenia Gravis). Patients with Hashimoto's thyroiditis are eligible to go on study. Active, known, or suspected autoimmune disease. Patients with an autoimmune paraneoplastic syndrome requiring concurrent immunosuppressive treatment are excluded. Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
  • A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study entry. Corticosteroids with minimal systemic absorption (inhaled or topical steroids) and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease
  • Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways)
  • Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
  • Previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, melanoma, or breast) unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period
  • Known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug(s) administration or interfere with the interpretation of safety results
  • Major surgery or significant traumatic injury that is not recovered at least 14 days before the initiation of prostate radiation therapy
  • Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBVsAg) test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection
  • Individuals with a positive test for HCV antibody but no detection of HCV RNA indicating no current infection are eligible
  • Known medical history of testing positive for human immunodeficiency virus (HIV) or known medical history of acquired immunodeficiency syndrome (AIDS)
  • Inadequate hematologic function; hepatic function; pancreatic function
  • History of allergy or hypersensitivity to any of the study drugs or study drug components.
  • Uncontrolled intercurrent illnesses including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness.
  • Social situations that could limit the patient's compliance with study requirements.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03543189

Layout table for location information
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Angelina Fink    813-745-2588    angelina.fink@moffitt.org   
Principal Investigator: Kosj Yamoah, M.D., Ph.D.         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Bristol-Myers Squibb
Layout table for investigator information
Principal Investigator: Kosj Yamoah, M.D., Ph.D. H. Lee Moffitt Cancer Center and Research Institute
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT03543189    
Other Study ID Numbers: MCC-19435
CA209-9MJ ( Other Identifier: Bristol-Myers Squibb Protocol Number )
First Posted: June 1, 2018    Key Record Dates
Last Update Posted: November 14, 2022
Last Verified: November 2022

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Gleason Group 5
Advanced Stage Prostate Cancer
Oligometastaic Disease
Androgen Deprivation Therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Prostatic Diseases
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs