Nivolumab with Radiation Therapy and Androgen Deprivation Therapy in Treating Patients with Gleason Group 5 Prostate Cancer

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
• Eastern Cooperative Oncology Group (ECOG) performance status: 0-1
• Diagnosed with grade group 5 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, when available
• Patients with oligometastatic 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
• Absolute neutrophil count > 1,500/uL (Patients being treated with nivolumab)
• Hemoglobin > 9 g/dL (Patients being treated with nivolumab)
• Platelets > 100,000/uL (Patients being treated with nivolumab)
• Total bilirubin =< 1.5 mg/dL X institutional upper limits of normal (ULN) (Patients being treated with nivolumab)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 3 X institutional ULN (Patients being treated with nivolumab)
• Serum creatinine of =< 1.5 X ULN or creatinine clearance > 40 mL/minute (using Cockcroft/Gault formula) (Patients being treated with nivolumab)
• Males who are sexually active with women of childbearing potential (WOCBP) 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; b) Azoospermic males are exempt from contraceptive requirements * 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)
• HIGHLY EFFECTIVE METHODS OF CONTRACEPTION At a minimum, participants must agree to the use of one highly effective method of contraception as listed below: Highly effective methods of contraception have a failure rate of < 1% when used consistently and correctly. Female partners of male participants who are WOCBP are expected to use one of the highly effective methods of contraception listed below. Male participants must inform their female partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner. Contraception methods are as follows: * Progestogen-only hormonal contraception associated with inhibition of ovulation * Hormonal methods of contraception, including oral contraceptive pills containing combined estrogen + progesterone, vaginal ring, injectables, implants, and intrauterine devices (IUDs) such as Mirena * Nonhormonal IUDs, such as ParaGard * Bilateral tubal occlusion * Vasectomized partner with documented azoospermia 90 days after procedure ** Vasectomized partner is a highly effective birth control method provided the vasectomized partner has received medical assessment of the surgical success * Intrauterine hormone-releasing system (IUS) * Complete abstinence ** Complete abstinence is defined as the complete avoidance of heterosexual intercourse ** Complete abstinence is an acceptable form of contraception for all study drugs and must be used throughout the duration of the study treatment (plus 5 half-lives of the investigational drug plus 30 days) ** It is not necessary to use any other method of contraception when complete abstinence is elected ** Acceptable alternate methods of highly effective contraception must be discussed in the event that the participant chooses to forego complete abstinence ** The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant * UNACCEPTABLE METHODS OF CONTRACEPTION 1) Periodic abstinence (calendar, symptothermal, post-ovulation methods) 2) Withdrawal (coitus interruptus) 3) Spermicide only 4) Lactation amenorrhea method (LAM)

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 (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., 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)
• Absolute neutrophil count (ANC) < 1,500/mm^3
• Platelet count < 100,000/mm^3, or
• Hemoglobin level < 9.0 g/dL
• Inadequate hepatic function as defined by either: * Total bilirubin level > 1.5 times the ULN (except patients with Gilbert syndrome, who are excluded if total bilirubin >= 3 times ULN), or * AST and ALT levels >= 3.0 times the ULN or >= 5 times the ULN if liver metastases are present
• Inadequate pancreatic function as defined by either: * Lipase > 1.5 ULN. Participants with lipase > 1.5 ULN may enroll if there are neither clinical nor radiographic signs of a pancreatitis * Amylase > 1.5 ULN. Participants with amylase > 1.5 ULN may enroll if there are neither clinical nor radiographic signs of a pancreatitis
• 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