Clinical Trials /

Nivolumab and BMS-986253 for Hormone-Sensitive Prostate Cancer (MAGIC-8)

NCT03689699

Description:

MAGIC-8 is a two-arm, multicenter, phase 1b/2 study to assess the efficacy of immunotherapy with either Nivolumab (anti-PD-1) or Nivolumab plus BMS-986253 combined with ADT using Degarelix (LHRH antagonist) for men with hormone-sensitive prostate cancer and a rising prostate-sepcific antigen (PSA). The purpose of this study is to see whether immunotherapy with either Nivolumab alone or Nivolumab plus BMS-986253 combined with Degarelix, which suppresses testosterone, is safe and can decrease the chance that the cancer will come back. The primary objectives are to 1) determine the rate of PSA recurrence defined as a PSA >0.2ng/ml for radical prostatectomy patients or PSA >2.0ng/ml for patients who received primary radiation therapy at a time point of 10 months after start of therapy; and 2) determine the safety and tolerability of either nivolumab or nivolumab plus BMS-986253 in combination with degarelix in men with hormone-sensitive prostate cancer. The secondary objectives include determining relapse-free survival (RFS) and % change in PSA to immunotherapy alone.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab and BMS-986253 for Hormone-Sensitive Prostate Cancer (MAGIC-8)
  • Official Title: Randomized Phase 1b/2 Study of Nivolumab or Nivolumab Plus BMS-986253 in Combination With Intermittent Androgen Deprivation Therapy in Men With Hormone-Sensitive Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: AAAR7949
  • NCT ID: NCT03689699

Conditions

  • Prostate Cancer
  • Adenocarcinoma of the Prostate

Interventions

DrugSynonymsArms
NivolumabOpdivo®Arm A: Nivolumab alone
DegarelixFirmagon®Arm A: Nivolumab alone
BMS-986253HuMax IL-8Arm B: Nivolumab plus BMS-986253

Purpose

MAGIC-8 is a two-arm, multicenter, phase 1b/2 study to assess the efficacy of immunotherapy with either Nivolumab (anti-PD-1) or Nivolumab plus BMS-986253 combined with ADT using Degarelix (LHRH antagonist) for men with hormone-sensitive prostate cancer and a rising prostate-sepcific antigen (PSA). The purpose of this study is to see whether immunotherapy with either Nivolumab alone or Nivolumab plus BMS-986253 combined with Degarelix, which suppresses testosterone, is safe and can decrease the chance that the cancer will come back. The primary objectives are to 1) determine the rate of PSA recurrence defined as a PSA >0.2ng/ml for radical prostatectomy patients or PSA >2.0ng/ml for patients who received primary radiation therapy at a time point of 10 months after start of therapy; and 2) determine the safety and tolerability of either nivolumab or nivolumab plus BMS-986253 in combination with degarelix in men with hormone-sensitive prostate cancer. The secondary objectives include determining relapse-free survival (RFS) and % change in PSA to immunotherapy alone.

Detailed Description

      Prostate cancer is common and remains a major cause of death in men. Following local therapy
      with surgery or radiation, a significant number of men recur either with a rising PSA only
      (biochemical recurrence (BCR)) or clear metastatic disease on imaging. Although androgen
      deprivation therapy (ADT) is a frequently used and effective treatment for prostate cancer,
      it is associated with significant side effects including fatigue, hot flashes, decreased
      libido and bone loss. Therefore, new approaches to decrease the time on ADT are crucial to
      improving quality of life for men with prostate cancer.

      Once initiated, ADT can be given either continuously or intermittently. However, even with an
      intermittent approach the ADT-free interval typically decreases with each cycle and most men
      eventually develop castration resistance. Therefore new treatment strategies are needed to
      improve disease control while minimizing ADT exposure for men with early prostate cancer.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A: Nivolumab aloneExperimentalMen with hormone-sensitive prostate cancer will receive Nivolumab alone every 4 weeks for 8 weeks (2 doses), followed by Nivolumab + Degarelix every 4 weeks for 16 weeks (4 doses).
  • Nivolumab
  • Degarelix
Arm B: Nivolumab plus BMS-986253ExperimentalMen with hormone-sensitive prostate cancer will receive Nivolumab plus BMS-986253 every 4 weeks for 8 weeks (2 doses), followed by Nivolumab + BMS-986253 + Degarelix every 4 weeks for 16 weeks (4 doses).
  • Nivolumab
  • Degarelix
  • BMS-986253

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥18 years.

          -  Histologically confirmed adenocarcinoma of the prostate.

          -  Previously undergone primary therapy for prostate cancer (radical prostatectomy (RP)
             or external beam radiation (XRT) or RP + XRT). Salvage XRT following RP ≥ 6 months
             prior to registration is allowed.

          -  Rising PSA (two consecutive values ≥2.0 ng/mL above the PSA nadir taken ≥3 weeks
             apart). PSA level of 2-25 ng/mL (PSA up to 50 is allowed for patients undergoing pre-
             and on-treatment biopsies).

          -  For the biopsy sub-groups, subjects must be willing to undergo pre- and on-treatment
             biopsies.

          -  PSA Doubling Time (PSADT) ≤12 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1 or Karnofsky score
             ≥70.

          -  Adequate bone marrow, hepatic, and renal function.

          -  Willingness to use barrier contraception during treatment.

          -  Willingness to provide written informed consent and HIPAA authorization.

        Exclusion Criteria:

          -  Received any experimental immunotherapy on an experimental clinical trial ≤ 1 year
             prior to registration.

          -  PSA > 25 at time of enrollment (or PSA >50 for patients receiving pre- and
             on-treatment biopsies).

          -  Other histologic types of prostate cancers such as ductal, sarcomatous, lymphoma,
             small cell, and neuroendocrine tumors

          -  Received salvage XRT ≤ 6 months prior to registration

          -  Received ADT ≤ 6 months prior to registration

          -  Received any form of chemotherapy ≤ 90 days prior to registration

          -  Received granulocyte colony-stimulating factor or granulocyte-macrophage
             colony-stimulating factor (GM-CSF) ≤ 90 days prior to registration

          -  Any major surgery requiring general anesthesia ≤ 28 days prior to registration.

          -  Any other concurrent or prior treatment for prostate cancer ≤ 28 days prior to
             registration.

          -  An active infection requiring parenteral antibiotic therapy or causing fever
             (temperature > 100.5 F or 38.1 C) within 1 week prior to registration.

          -  Prior systemic, ongoing immunosuppressive therapy ≤ 14 days prior to study treatment
             administration (except for adrenal replacement steroid doses ≤ 10mg daily prednisone
             equivalent in the absence of active autoimmune disease or a short course of steroids
             (<5 days) up to 7 days prior to initiating study treatment).

          -  Prior use of experimental agents for prostate cancer

          -  Prior participation in an anti-interleukin 8 (IL8) clinical study

          -  A candidate is scheduled or likely to be scheduled for salvage external beam XRT or
             surgery for prostate cancer during the study period

          -  Concomitant treatment with other hormonal therapy or 5α-reductase inhibitors (prior
             use of these agents is allowed if ≥3 months prior to registration).

          -  History of known or suspected autoimmune disease with the following exceptions:

               -  Asthma and/or allergic rhinitis (seasonal allergies)

               -  Vitiligo

               -  Resolved childhood atopic dermatitis

               -  Psoriasis not requiring systemic treatment, or conditions not expected to recur
                  in the absence of an external trigger.

               -  Residual hypothyroidism due to an autoimmune condition only requiring hormone
                  replacement

               -  Euthyroid participants with a history of Grave's disease (participants with
                  suspected autoimmune thyroid disorders must be negative for thyroglobulin and
                  thyroid peroxidase antibodies and thyroid stimulating immunoglobulin (Ig) prior
                  to the first dose of study treatment).

               -  Type 1 diabetes mellitus

          -  History of malignancy within the last 2 years (except non-melanoma skin cancers and
             superficial bladder cancer) and for which no additional therapy is required or
             anticipated to be required during the study period.

          -  Uncontrolled major active infectious, cardiovascular, pulmonary, hematologic, or
             psychiatric illnesses that would make the patient a poor study candidate

          -  Known prior or current history of HIV and/or hepatitis B/C

          -  Prior organ allograft
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of PSA recurrence
Time Frame:Up to 10 months after completion of therapy
Safety Issue:
Description:Defined as a PSA >0.2ng/ml for radical prostatectomy patients or PSA >2.0ng/ml for patients who received primary radiation therapy at a time point of 10 months after start of therapy.

Secondary Outcome Measures

Measure:Percentage change in PSA
Time Frame:Baseline, 8 weeks
Safety Issue:
Description:Determine the % change in PSA in response to immunotherapy by comparing the PSA prior to and following 8 weeks of immunotherapy and before initiation of ADT
Measure:Relapse-free survival (RFS)
Time Frame:Up to two years
Safety Issue:
Description:Relapse defined as a PSA >0.2ng/ml for radical prostatectomy patients or PSA >2.0ng/ml for patients who received primary radiation therapy.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Charles G. Drake

Trial Keywords

  • Immunotherapy
  • Nivolumab
  • BMS-986253
  • Degarelix
  • HuMax IL-8

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