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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03689699
Recruitment Status : Recruiting
First Posted : September 28, 2018
Last Update Posted : July 25, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Charles G. Drake, Columbia University

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Prostate Cancer Adenocarcinoma of the Prostate Drug: Nivolumab Drug: Degarelix Drug: BMS-986253 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The study will include a total of approximately 30 patients per arm to achieve at least 23 evaluable patients per arm.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 11, 2018
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A: Nivolumab alone
Men 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).
Drug: Nivolumab
A dose of 480mg every 4 weeks as a 30 minute IV infusion for 6 doses has been selected for this study. 6 total doses.
Other Name: Opdivo®

Drug: Degarelix
Standard treatment at a dose of 240mg subcutaneously (SQ) as a loading dose followed by 80mg SQ every 4 weeks for 4 doses.
Other Name: Firmagon®

Experimental: Arm B: Nivolumab plus BMS-986253
Men 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).
Drug: Nivolumab
A dose of 480mg every 4 weeks as a 30 minute IV infusion for 6 doses has been selected for this study. 6 total doses.
Other Name: Opdivo®

Drug: Degarelix
Standard treatment at a dose of 240mg subcutaneously (SQ) as a loading dose followed by 80mg SQ every 4 weeks for 4 doses.
Other Name: Firmagon®

Drug: BMS-986253
BMS-986253 (also referred to as anti-IL8 mAb or HuMax IL8) is a fully human-sequence IgG1κ monoclonal antibody (mAb) directed against human interleukin-8 (IL-8). Subjects will be treated with an intravenous (IV) flat dose of 2400mg every 2 weeks.
Other Name: HuMax IL-8




Primary Outcome Measures :
  1. Rate of PSA recurrence [ Time Frame: Up to 10 months after completion of therapy ]
    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.

  2. Number of adverse events [ Time Frame: Up to two years ]
    Adverse event that are serious in nature and related to the investigational product will be recorded.


Secondary Outcome Measures :
  1. Percentage change in PSA [ Time Frame: Baseline, 8 weeks ]
    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

  2. Relapse-free survival (RFS) [ Time Frame: Up to two years ]
    Relapse defined as a PSA >0.2ng/ml for radical prostatectomy patients or PSA >2.0ng/ml for patients who received primary radiation therapy.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03689699


Contacts
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Contact: Lisa Olmos 212.342.5162 cancerclinicaltrials@cumc.columbia.edu

Locations
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United States, New York
Weill Cornell Medical Center Not yet recruiting
New York, New York, United States, 10021
Contact: David Nanus, MD    646-962-2072    dnanus@med.cornell.edu   
Principal Investigator: David Nanus, MD         
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Lisa Olmos    212-342-5162    cancerclinicaltrials@cumc.columbia.edu   
Principal Investigator: Charles G. Drake, MD, PhD         
Sub-Investigator: Matthew Dallos, MD         
United States, Pennsylvania
Sidney Kimmel Cancer Center- Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Kevin Kelly, DO    215-955-8874    kevin.kelly@jefferson.edu   
Principal Investigator: Kevin Kelly, DO         
Sponsors and Collaborators
Charles G. Drake
Bristol-Myers Squibb
Investigators
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Principal Investigator: Charles G. Drake, MD, PhD Columbia University
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Responsible Party: Charles G. Drake, Professor of Medicine, Columbia University
ClinicalTrials.gov Identifier: NCT03689699    
Other Study ID Numbers: AAAR7949
First Posted: September 28, 2018    Key Record Dates
Last Update Posted: July 25, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Charles G. Drake, Columbia University:
Immunotherapy
Nivolumab
BMS-986253
Degarelix
HuMax IL-8
Additional relevant MeSH terms:
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Prostatic Neoplasms
Adenocarcinoma
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents