Clinical Trial 19435

• Overview

  Study Title:

  Combination of Nivolumab Immunotherapy with Radiation Therapy and Androgen Deprivation Therapy in the Management of Gleason Group 5 Prostate Cancer

  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.

  Objective:

  Primary Objectives: Phase I safety lead in: To determine the safety and feasibility of combining nivolumab with RT and ADT in patients with Gleason Group 5 PCa. Phase II: To determine the 2-year biochemical relapse free survival rate of nivolumab combined with definitive RT in patients with Gleason Group 5 PCa. Secondary Objectives: - To observe and record anti-tumor activity as defined by "time to PSA nadir". Although the clinical benefit of nivolumab has not yet been established in PCa, the intent of offering this treatment is to provide a possible therapeutic benefit, and thus the patient will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability. - To assess the acute and late nonhematologic and hematologic toxicity profile - To describe patient-reported outcomes including EPIC, AUA Symptom Index, and SHIM for patients treated with nivolumab, combined with RT and ADT. Exploratory Objectives: - To understand the impact of nivolumab on the temporal expression pattern of immune ligands in prostate tissue. - To understand the immune milieu (T cell repertoire, macrophage and NK cells), T cell dynamics, and clonal shifts in the presence of nivolumab and RT. - To identify blood biomarkers that immune-mediated treatment response in PCa.

• Treatments

  Therapies:

  Hormonal Therapy; Immunotherapy; Radiotherapy

  Medications:

  BMS-936558 (Nivolumab); Casodex (Bicalutamide); Lupron (leuprolide acetate); Nivolumab (Opdivo)

• 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 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
  • Patients 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 and motor neuropathy considered to be of autoimmune origin. 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 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 or other immunosuppressive medications within 14 days of study entry. Some exceptions apply.
  • 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

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