Prostate CancerPhase 1/2NCT03543189
Combination of Nivolumab Immunotherapy With Radiation Therapy and Androgen Deprivation Therapy
A Phase 1/2 study testing Nivolumab, Brachytherapy and External Beam Radiation Therapy in people with Prostate Cancer and Prostate Disease, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer, Prostate Disease
- What is being tested?
- Nivolumab, Brachytherapy and External Beam Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Oct 2018to 19 Jun 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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).
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: Combination of Nivolumab Immunotherapy With Radiation Therapy and Androgen Deprivation Therapy in the Management of Gleason Group 5 Prostate Cancer
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.
- Conditions
- Prostate Cancer, Prostate Disease
- Being tested
- Nivolumab, Brachytherapy, External Beam Radiation Therapy, Androgen Deprivation Therapy
- Keywords
- Gleason Group 5, PCa, Advanced Stage Prostate Cancer, Immunotherapy, Oligometastaic Disease, Brachytherapy, Androgen Deprivation Therapy
- Medical subject headings
- Prostatic Neoplasms, Prostatic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo®
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.
BrachytherapyRadiation
Also called HDR 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.
External Beam Radiation TherapyRadiation
Also called Radiotherapy, EBRT
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.
Androgen Deprivation TherapyDrug
Also called ADT
Standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Combination Therapy | Experimental | Post androgen deprivation therapy (ADT), participants will receive nivolumab, HDR brachytherapy and external beam radiation therapy, followed by a 2 year follow-up period. Receives: Drug: Nivolumab; Radiation: Brachytherapy; Radiation: External Beam Radiation Therapy; Drug: Androgen Deprivation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Safety Run In - Rate of Dose Limiting Toxicity (CTCAE V5.0)
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
Measured: Up to 12 weeks after initiation of Nivolumab
Phase II: Relapse Free Survival Rate
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.
Measured: Up to 2 years
Secondary outcomes (1)
Time to PSA Nadir
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.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2018
- Study start3 Oct 2018
- Primary completion19 Jun 2026
- Study completion19 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Kosj Yamoah, M.D., Ph.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03543189
- Sponsor's protocol ID
- MCC-19435
- Other IDs
- CA209-9MJ
- Status last verified
- Sep 2026
- First submitted
- 18 May 2018
- Last updated
- 16 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Yuan Z, Fernandez D, Dhillon J, Abraham-Miranda J, Awasthi S, Kim Y, Zhang J, Jain R, Serna A, Pow-Sang JM, Poch M, Li R, Manley B, Fink A, Naghavi A, Torres-Roca JF, Grass GD, Kim S, Latifi K, Hunt D, Johnstone PAS, Yamoah K. Proof-of-principle Phase I results of combining nivolumab with brachytherapy and external beam radiation therapy for Grade Group 5 prostate cancer: safety, feasibility, and exploratory analysis. Prostate Cancer Prostatic Dis. 2021 Mar;24(1):140-149. doi: 10.1038/s41391-020-0254-y. Epub 2020 Jul 10.
PubMed 32651467
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination of Nivolumab Immunotherapy With Radiation Therapy and Androgen Deprivation Therapy in the Management of Gleason Group 5 Prostate Cancer
- ClinicalTrials.gov ID
- NCT03543189
- Acronym / sponsor ID
- MCC-19435
- Conditions
- Prostate Cancer, Prostate Disease
- Keywords
- Gleason Group 5, PCa, Advanced Stage Prostate Cancer, Immunotherapy, Oligometastaic Disease, Brachytherapy, Androgen Deprivation Therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 3 Oct 2018 (actual)
- Primary completion
- 19 Jun 2026 (actual)
- Study completion
- 19 Jun 2026 (actual)
- First posted
- 1 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination Therapy | Experimental | Drug: Nivolumab, Radiation: Brachytherapy, Radiation: External Beam Radiation Therapy, Drug: Androgen Deprivation TherapyPost androgen deprivation therapy (ADT), participants will receive nivolumab, HDR brachytherapy and external beam radiation therapy, followed by a 2 year follow-up period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: Opdivo®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. | Drug | Combination Therapy |
| BrachytherapyAlso: HDR BrachytherapyHigh 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. | Radiation | Combination Therapy |
| External Beam Radiation TherapyAlso: Radiotherapy, EBRTExternal 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. | Radiation | Combination Therapy |
| Androgen Deprivation TherapyAlso: ADTStandard of care. | Drug | Combination Therapy |
Primary outcome
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
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.
1 secondary outcome
Time to PSA Nadir
Time frame: Up to 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2026.
- Derived from this study: PubMed 32651467Yuan Z, Fernandez D, Dhillon J, Abraham-Miranda J, Awasthi S, Kim Y, Zhang J, Jain R, Serna A, Pow-Sang JM, Poch M, Li R, Manley B, Fink A, Naghavi A, Torres-Roca JF, Grass GD, Kim S, Latifi K, Hunt D, Johnstone PAS, Yamoah K. Proof-of-principle Phase I results of combining nivolumab with brachytherapy and external beam radiation therapy for Grade Group 5 prostate cancer: safety, feasibility, and exploratory analysis. Prostate Cancer Prostatic Dis. 2021 Mar;24(1):140-149. doi: 10.1038/s41391-020-0254-y. Epub 2020 Jul 10.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kosj Yamoah, M.D., Ph.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Nivolumab, Brachytherapy and External Beam Radiation Therapy in people with Prostate Cancer and Prostate Disease, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Safety Run In - Rate of Dose Limiting Toxicity (CTCAE V5.0) (time frame: Up to 12 weeks after initiation of Nivolumab). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03543189, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2026.