This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Participants With Metastatic Prostate Cancer (MAGNITUDE)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03748641
Recruitment Status : Active, not recruiting
First Posted : November 21, 2018
Results First Posted : October 4, 2023
Last Update Posted : March 28, 2024
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to evaluate the effectiveness of niraparib in combination with abiraterone acetate plus prednisone (AAP) compared to AAP and placebo.

Condition or disease Intervention/treatment Phase
Castration-Resistant Prostatic Cancer Drug: Niraparib Drug: Abiraterone Acetate Drug: Prednisone Drug: Placebo Drug: New Formulation of Niraparib and Abiraterone Acetate (AA) Phase 3

Detailed Description:
This study will assess efficacy and safety of niraparib in combination with AAP for the treatment of participants with metastatic castration resistant prostate cancer. Niraparib is an orally available, highly selective poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, with potent activity against PARP-1 and PARP-2 deoxyribonucleic acid (DNA)-repair polymerases. AA is a pro-drug of abiraterone and selectively inhibits the enzyme 17 alpha-hydroxylase/C17,20-lyase (CYP17), which is found in the testes and adrenals, as well as in prostate tissues and tumors. In participants with metastatic prostate cancer, DNA-repair anomalies are identified in approximately 15 percent (%) to 20% of tumors. The study will consist of 5 phases: a prescreening phase for biomarker evaluation only, a screening phase, a treatment phase, a follow up phase, and an extension phase (either open-label extension [OLE] or long-term extension [LTE]). During the prescreening phase participants will be evaluated for homologous recombination repair (HRR) gene alteration status and then will be assigned to one of the 2 cohorts based on their biomarker status. Treatment will be administered daily and is planned to be continuous until disease progression, unacceptable toxicity, death, or the sponsor terminates the study. Efficacy, pharmacokinetics, biomarkers, participants reported outcomes and safety will be assessed. The total duration of study will be approximately 66 months.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 765 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Placebo-controlled, Double-blind Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone in Subjects With Metastatic Prostate Cancer
Actual Study Start Date : January 25, 2019
Actual Primary Completion Date : October 8, 2021
Estimated Study Completion Date : February 19, 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1: Participants with mCRPC and HRR Gene Alteration
Participants with L1 metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alteration will receive combination of niraparib 200 milligrams (mg) or matching placebo and abiraterone acetate (AA) 1000 mg plus prednisone 10 mg. In the open label extension (OLE) phase participants earlier receiving the combination of niraparib and AAP may continue to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg and those receiving placebo and AAP may cross over depending on the outcome of study to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg.
Drug: Niraparib
Participants will receive niraparib 200 mg capsules once daily.
Other Name: JNJ-64091742

Drug: Abiraterone Acetate
Participants will receive AA 1000 mg tablets once daily.

Drug: Prednisone
Participants will receive prednisone 10 mg tablets daily.

Drug: Placebo
Participants will receive matching placebo once daily.

Experimental: Cohort 2: Participants with mCRPC and No HRR Gene Alteration
Participants with L1 mCRPC and no HRR Gene alteration will receive combination of niraparib 200 mg or matching placebo and AA 1000 mg plus prednisone 10 mg. In the OLE phase participants earlier receiving the combination of niraparib and AAP may continue to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg and those receiving placebo and AAP may cross over depending on the outcome of study to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg.
Drug: Niraparib
Participants will receive niraparib 200 mg capsules once daily.
Other Name: JNJ-64091742

Drug: Abiraterone Acetate
Participants will receive AA 1000 mg tablets once daily.

Drug: Prednisone
Participants will receive prednisone 10 mg tablets daily.

Drug: Placebo
Participants will receive matching placebo once daily.

Experimental: Cohort 3 (Open-label): Participants with mCRPC
Participants with mCRPC will receive a new formulation of niraparib 200 mg and AA 1000 mg tablets plus prednisone 10 mg.
Drug: Prednisone
Participants will receive prednisone 10 mg tablets daily.

Drug: New Formulation of Niraparib and Abiraterone Acetate (AA)
Participants will receive a new formulation of niraparib 200 mg and AA 1000 mg tablets once daily.




Primary Outcome Measures :
  1. Cohort 1: Radiographic Progression-Free Survival (rPFS) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to 32 months ]
    As per BICR, rPFS is time interval from the date of randomization to radiographic progression or death, whichever occurs first. Radiographic progression was determined by: 1) progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) as per response evaluation criteria in solid tumors (RECIST) 1.1; 2) Progression of bone lesions observed by bone scan based on prostate cancer working group 3 (PCWG3) criteria. PCWG3 criteria: bone progression was confirmed by subsequent scan greater than or equal to (>=) 6 weeks later. Week 8 scan was baseline to which all subsequent scans were compared to determine progression. Confirmatory scan >=2 new lesions indicate progression; scan does not show >= 2 new lesions means no progression. If Week 8 scan less than (<) 2 new bone lesions compared to baseline, the initial scan >=2 new lesions compared to Week 8 scan indicates progression if confirmed by subsequent scan >=6 weeks later.


Secondary Outcome Measures :
  1. Cohort 1: Overall Survival (OS) [ Time Frame: Up to 97 months ]
  2. Cohort 1: Time to Symptomatic Progression [ Time Frame: Up to 97 months ]
  3. Cohort 1: Time to Initiation of Cytotoxic Chemotherapy [ Time Frame: Up to 97 months ]
  4. Observed Plasma Concentrations of Niraparib [ Time Frame: Up to 97 months ]
  5. Observed Plasma Concentrations of Abiraterone [ Time Frame: Up to 97 months ]
  6. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to 96 months ]
  7. Number of Participants With Treatment-Emergent Adverse Events by Severity [ Time Frame: Up to 96 months ]
  8. Number of Participants With Abnormalities in Laboratory Values [ Time Frame: Up to 96 months ]


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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HRR gene alteration (as identified by the sponsor's required assays) as follows:

    1. Cohort 1: positive for HRR gene alteration
    2. Cohort 2: not positive for DRD (that is, HRR gene alteration)
    3. Cohort 3: eligible by HRR status
  • Metastatic disease documented by positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI)
  • Metastatic prostate cancer in the setting of castrate levels of testosterone less than or equal to (<=) 50 nanogram per deciliter (ng/dL) on a gonadotropin releasing hormone analog (GnRHa) or bilateral orchiectomy
  • Able to continue GnRHa during the study if not surgically castrate
  • Score of <= 3 on the brief pain inventory-short form (BPI-SF) question number 3 (worst pain in last 24 hours)

Exclusion Criteria:

  • Prior treatment with a poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor
  • Systemic therapy (that is, novel second-generation AR-targeted therapy such as enzalutamide, apalutamide, or darolutamide; taxane-based chemotherapy, or more than 4 months of abiraterone acetate plus prednisone [AAP] prior to randomization) in the metastatic castration-resistant prostate cancer (mCRPC) setting; or AAP outside of the mCRPC setting
  • Symptomatic brain metastases
  • History or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
  • Other prior malignancy (exceptions: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) <= 2 years prior to randomization, or malignancy that currently requires active systemic therapy

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): NCT03748641


Locations
Show Show 318 study locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Layout table for investigator information
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  Study Documents (Full-Text)

Documents provided by Janssen Research & Development, LLC:
Study Protocol  [PDF] September 30, 2021
Statistical Analysis Plan  [PDF] June 2, 2022

Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03748641    
Other Study ID Numbers: CR108534
2017-003364-12 ( EudraCT Number )
64091742PCR3001 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: November 21, 2018    Key Record Dates
Results First Posted: October 4, 2023
Last Update Posted: March 28, 2024
Last Verified: March 2024

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Prostatic Neoplasms, Castration-Resistant
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Genital Diseases
Urogenital Diseases
Prostatic Diseases
Male Urogenital Diseases
Prednisone
Abiraterone Acetate
Niraparib
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Cytochrome P-450 Enzyme Inhibitors
Poly(ADP-ribose) Polymerase Inhibitors