Clinical Trials /

Combination of Nivolumab Immunotherapy With Radiation Therapy and Androgen Deprivation Therapy

NCT03543189

Description:

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.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: MCC-19435
  • SECONDARY ID: CA209-9MJ
  • NCT ID: NCT03543189

Conditions

  • Prostate Cancer
  • Prostate Disease

Interventions

DrugSynonymsArms
NivolumabOpdivo®Combination Therapy
Androgen Deprivation TherapyADTCombination Therapy

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Combination TherapyExperimentalPost androgen deprivation therapy (ADT), participants will receive nivolumab, HDR brachytherapy and external beam radiation therapy, followed by a 2 year follow-up period.
  • Nivolumab
  • 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

          -  Must have normal organ function

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Safety Run In - Rate of Dose Limiting Toxicity (CTCAE V5.0)
Time Frame:Up to 12 weeks after initiation of Nivolumab
Safety Issue:
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

Secondary Outcome Measures

Measure:Time to PSA Nadir
Time Frame:Up to 2 years
Safety Issue:
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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • Gleason Group 5
  • PCa
  • Advanced Stage Prostate Cancer
  • Immunotherapy
  • Oligometastaic Disease
  • Brachytherapy
  • Androgen Deprivation Therapy

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