- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03689699
Nivolumab and BMS-986253 for Hormone-Sensitive Prostate Cancer (MAGIC-8)
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
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-specific 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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Georgia
-
Atlanta, Georgia, United States, 30322
- Winship Cancer Institute, Emory University
-
-
New York
-
New York, New York, United States, 10032
- Columbia University Irving Medical Center
-
New York, New York, United States, 10021
- Weill Cornell Medical Center
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19107
- Sidney Kimmel Cancer Center- Thomas Jefferson University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Histologically documented prostatic adenocarcinoma confirmed by a pathology report from prostate biopsy or a radical prostatectomy specimen.
- Age ≥18 years
- Previously undergone primary therapy for prostate cancer. Salvage XRT or cryotherapy following primary therapy ≥ 6 months prior to randomization is allowed.
A rising PSA defined as the following:
- If the subject's primary therapy was RP (radical prostatectomy) (with or without adjuvant or salvage XRT), rising PSA is defined as 2 consecutive rising values above 0.2 ng/mL, each taken ≥ 3 weeks apart, and the last value ≥ 2.0 ng/mL
- If the subject received other primary therapies (e.g. XRT, cryosurgery, brachytherapy), rising PSA is defined per the Phoenix definition, i.e., 2 consecutive rising values above the PSA nadir plus 2.0 ng/mL.
- For the biopsy sub-groups, patients must be willing to undergo pre and on- treatment biopsies.
- PSADT ≤ 12 months. PSADT(prostate-specific antigen doubling time) will be determined from all non-zero PSA values collected preferably, however not limited to, from the 12 months prior to randomization. To calculate PSADT, there must be at least THREE PSA values, with at least 4 weeks between each measurement. The PSADT will be computed from the formula: PSADT = (loge2)/k, with k being the estimated slope of the logarithm of PSA over time. The following web site may also be used: http://www.mskcc.org/applications/nomograms/prostate/PsaDoublingTime.aspx
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1, or Karnofsky score ≥ 70% (see Appendix A)
- Testosterone ≥ 150 ng/dL ≤ 28 days of prior to registration
Adequate bone marrow, hepatic, and renal function:
- White Blood Cell (WBC)>3,000 cells/mm3
- Absolute neutrophil count (ANC)>1,500 cells/mm3
- Hemoglobin >9.0 g/dL
- Platelet count >100,000 cells/mm3
- Serum creatinine <1.5 × upper limit of normal (ULN)
- Serum total bilirubin <1.5 × ULN
- ALT (alanine aminotransferase) <3 × ULN
- AST(aspartate aminotransferase) <3 × ULN
- Willingness to provide written informed consent and HIPAA authorization for the release of personal health information, and the ability to comply with the study requirements (note: HIPAA authorization will be included in the informed consent)
- Willingness to use barrier contraception during treatment plus 5 half-lives of nivolumab (~125 days) plus 90 days (duration of sperm turnover) for a total of 215 days post-treatment completion (azoospermic men are not exempt from contraceptive requirements)
Exclusion Criteria:
Received any experimental immunotherapy on an experimental clinical trial ≤ 1 year prior to randomization
- PSA > 50 at time of enrollment
- High volume disease defined as >5 bone metastases or lymph nodes >3cm in size.
- Histologic predominance of other types of prostate cancers such as sarcomatous, lymphoma, small cell, and neuroendocrine tumors (note: a maximum of 5 subjects with ductal prostate cancer will be allowed to enroll to each arm of study treatment across all sites).
- Received salvage XRT ≤ 6 months prior to randomization
- Received ADT ≤ 6 months prior to randomization
- Received any form of chemotherapy ≤ 90 days prior to randomization
- Received granulocyte colony-stimulating factor or GM-CSF ≤ 90 days prior to randomization
- Any major surgery requiring general anesthesia ≤ 28 days prior to randomization.
- Any other concurrent or prior treatment for prostate cancer ≤ 28 days prior to randomization.
- An active infection requiring parenteral antibiotic therapy or causing fever (temperature > 100.5 o F or 38.1 o C) within 1 week prior to randomization
- Prior systemic, ongoing immunosuppressive therapy ≤ 14 days prior to study treatment administration (except for adrenal replacement steroid doses ≤ 10mgdaily 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 participation in an anti-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 such as Dutasteride or Finasteride (prior use of these agents is allowed if ≥3 months prior to randomization).
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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).
|
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 Names:
Standard treatment at a dose of 240mg subcutaneously (SQ) as a loading dose followed by 80mg SQ every 4 weeks for 4 doses.
Other Names:
|
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).
|
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 Names:
Standard treatment at a dose of 240mg subcutaneously (SQ) as a loading dose followed by 80mg SQ every 4 weeks for 4 doses.
Other Names:
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 Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to 10 months after completion of therapy
|
Incidence of adverse events that are serious in nature and related to the investigational product.
Time Frame: Up to two years
|
All participants receiving at least one dose of the study drug will be evaluated for safety and toxicity.
Adverse events will be classified and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
|
Up to two years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Baseline, 8 weeks
|
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.
|
Up to two years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Mark N. Stein, MD, Columbia University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Male
- Prostatic Diseases
- Urogenital Diseases
- Male Urogenital Diseases
- Genital Diseases, Male
- Genital Diseases
- Prostatic Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Nivolumab
Other Study ID Numbers
- AAAR7949
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Prostate Cancer
-
Roswell Park Cancer InstituteRecruitingObesity | Overweight | Cancer Survivor | Prostate Adenocarcinoma | Stage I Prostate Cancer | Stage II Prostate Cancer | Stage III Prostate Cancer | Stage IV Prostate Cancer | Stage IIA Prostate Cancer | Stage IIB Prostate Cancer | Stage IVA Prostate Cancer | Stage IVB Prostate Cancer | Stage A Prostate Cancer | Stage... and other conditionsUnited States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...Regeneron Pharmaceuticals; Prostate Cancer FoundationWithdrawnStage III Prostate Cancer | Stage IV Prostate Cancer | Stage IVA Prostate Cancer | Stage IVB Prostate Cancer | Stage IIIA Prostate Cancer | Stage IIIB Prostate Cancer | Stage IIIC Prostate Cancer
-
Jonsson Comprehensive Cancer CenterProgenics Pharmaceuticals, Inc.TerminatedRandomized Trial of PSMA PET Scan Before Definitive Radiation Therapy for Prostate Cancer (PSMA-dRT)Stage II Prostate Cancer AJCC v8 | Stage IIIA Prostate Cancer AJCC v8 | Stage IIIB Prostate Cancer AJCC v8 | Stage IIC Prostate Cancer AJCC v8 | Stage III Prostate Cancer AJCC v8 | Stage IIIC Prostate Cancer AJCC v8 | Stage IIA Prostate Cancer AJCC v8 | Stage IIB Prostate Cancer AJCC v8 | Stage I Prostate...United States
-
University of Southern CaliforniaNational Cancer Institute (NCI); SanofiTerminatedDiarrhea | Recurrent Prostate Cancer | Hormone-resistant Prostate Cancer | Stage I Prostate Cancer | Stage III Prostate Cancer | Stage IV Prostate Cancer | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
-
Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI)CompletedRecurrent Prostate Cancer | Stage I Prostate Cancer | Stage III Prostate Cancer | Adenocarcinoma of the Prostate | Stage IV Prostate Cancer | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
-
Ryan Kohlbrenner, MDRadiological Society of North AmericaCompletedProstate Adenocarcinoma | Stage IV Prostate Cancer AJCC v8 | Prostate Carcinoma | Stage IIIA Prostate Cancer AJCC v8 | Stage IIIB Prostate Cancer AJCC v8 | Stage IIC Prostate Cancer AJCC v8 | Stage III Prostate Cancer AJCC v8 | Stage IIIC Prostate Cancer AJCC v8 | Stage IVA Prostate Cancer AJCC v8 | Stage...United States
-
Mayo ClinicNational Cancer Institute (NCI)WithdrawnStage I Prostate Cancer AJCC v8 | Stage II Prostate Cancer AJCC v8 | Stage IIIA Prostate Cancer AJCC v8 | Stage IIIB Prostate Cancer AJCC v8 | Stage IIC Prostate Cancer AJCC v8 | Stage III Prostate Cancer AJCC v8 | Stage IIIC Prostate Cancer AJCC v8 | Stage IIA Prostate Cancer AJCC v8 | Stage IIB Prostate...United States
-
Barbara Ann Karmanos Cancer InstituteGenentech, Inc.CompletedRecurrent Prostate Cancer | Stage I Prostate Cancer | Stage III Prostate Cancer | Adenocarcinoma of the Prostate | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
-
Ohio State University Comprehensive Cancer CenterRiverside Methodist HospitalCompletedStage I Prostate Cancer | Stage III Prostate Cancer | Stage IV Prostate Cancer | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
-
University of California, IrvineCompletedRecurrent Prostate Cancer | Stage I Prostate Cancer | Stage III Prostate Cancer | Adenocarcinoma of the Prostate | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
Clinical Trials on Nivolumab
-
Universitair Ziekenhuis BrusselNot yet recruiting
-
Brown UniversityBristol-Myers Squibb; The Miriam Hospital; Rhode Island Hospital; Women and Infants...Terminated
-
Bristol-Myers SquibbRecruitingMelanomaSpain, United States, Italy, Chile, Greece, Argentina
-
Baptist Health South FloridaBristol-Myers Squibb; NovoCure Ltd.TerminatedRecurrent GlioblastomaUnited States
-
HUYABIO International, LLC.Bristol-Myers SquibbRecruitingUnresectable or Metastatic Melanoma | Progressive Brain MetastasisSpain, United States, Italy, Japan, Belgium, France, New Zealand, Brazil, Korea, Republic of, Australia, Germany, Singapore, Czechia, Austria, South Africa, United Kingdom, Puerto Rico
-
Jason J. Luke, MDArray BioPharmaActive, not recruitingMelanoma | Renal Cell Carcinoma | Solid Tumor | Non-small Cell Lung Cancer | Head and Neck Squamous Cell CarcinomaUnited States
-
Michael B. Atkins, MDBristol-Myers Squibb; Hoosier Cancer Research NetworkActive, not recruitingAdvanced Renal Cell CarcinomaUnited States
-
Bristol-Myers SquibbCompletedLung CancerItaly, United States, France, Russian Federation, Spain, Argentina, Belgium, Brazil, Canada, Chile, Czechia, Germany, Greece, Hungary, Mexico, Netherlands, Poland, Romania, Switzerland, Turkey, United Kingdom
-
IRCCS San RaffaeleBristol-Myers SquibbRecruiting
-
National Health Research Institutes, TaiwanNational Taiwan University Hospital; Mackay Memorial Hospital; China Medical... and other collaboratorsRecruitingHepatocellular Carcinoma (HCC)Taiwan