Combination of Nivolumab Immunotherapy With Radiation Therapy and Androgen Deprivation Therapy
Primary Purpose
Prostate Cancer, Prostate Disease
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Nivolumab
Brachytherapy
External Beam Radiation Therapy
Androgen Deprivation Therapy
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring Gleason Group 5, PCa, Advanced Stage Prostate Cancer, Immunotherapy, Oligometastaic Disease, Brachytherapy, Androgen Deprivation Therapy
Eligibility Criteria
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.
Sites / Locations
- H. Lee Moffitt Cancer Center and Research InstituteRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Combination Therapy
Arm Description
Post androgen deprivation therapy (ADT), participants will receive nivolumab, HDR brachytherapy and external beam radiation therapy, followed by a 2 year follow-up period.
Outcomes
Primary Outcome Measures
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
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.
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT03543189
First Posted
May 18, 2018
Last Updated
September 21, 2023
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Bristol-Myers Squibb
1. Study Identification
Unique Protocol Identification Number
NCT03543189
Brief Title
Combination of Nivolumab Immunotherapy With Radiation Therapy and Androgen Deprivation Therapy
Official Title
Combination of Nivolumab Immunotherapy With Radiation Therapy and Androgen Deprivation Therapy in the Management of Gleason Group 5 Prostate Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 3, 2018 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Bristol-Myers Squibb
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer, Prostate Disease
Keywords
Gleason Group 5, PCa, Advanced Stage Prostate Cancer, Immunotherapy, Oligometastaic Disease, Brachytherapy, Androgen Deprivation Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
44 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Combination Therapy
Arm Type
Experimental
Arm Description
Post androgen deprivation therapy (ADT), participants will receive nivolumab, HDR brachytherapy and external beam radiation therapy, followed by a 2 year follow-up period.
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
Opdivo®
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
Brachytherapy
Other Intervention Name(s)
HDR Brachytherapy
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
External Beam Radiation Therapy
Other Intervention Name(s)
Radiotherapy, EBRT
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Androgen Deprivation Therapy
Other Intervention Name(s)
ADT
Intervention Description
Standard of care.
Primary Outcome Measure Information:
Title
Phase 1: Safety Run In - Rate of Dose Limiting Toxicity (CTCAE V5.0)
Description
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
Time Frame
Up to 12 weeks after initiation of Nivolumab
Title
Phase II: Relapse Free Survival Rate
Description
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.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Time to PSA Nadir
Description
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.
Time Frame
Up to 2 years
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kosj Yamoah, M.D., Ph.D.
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amalin Asous
Phone
813-745-6470
Email
Amalin.Asous@moffitt.org
First Name & Middle Initial & Last Name & Degree
Kosj Yamoah, M.D., Ph.D.
12. IPD Sharing Statement
Citations:
PubMed Identifier
32651467
Citation
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.
Results Reference
derived
Links:
URL
https://www.moffitt.org/clinical-trials-research/clinical-trials/?gclid=EAIaIQobChMImIymzIa-9gIVAZ2GCh3uzAWJEAAYASAAEgI0ovD_BwE
Description
Moffitt Cancer Center Clinical Trials website
Learn more about this trial
Combination of Nivolumab Immunotherapy With Radiation Therapy and Androgen Deprivation Therapy
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