TriangleNCT03748641 · CITED IN SOURCE DOCUMENTS
A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Participants With Metastatic Prostate Cancer
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2026-07-31
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Cohort 1: Radiographic Progression-Free Survival (rPFS) as Assessed by Blinded Independent Central Review (BICR)
Cohort 1 Breast Cancer Gene (BRCA) Subgroup: Radiographic Progression-Free Survival (rPFS) as Assessed by Blinded Independent Central Review (BICR)
Cohort 1: Overall Survival (OS)
Cohort 1: Time to Symptomatic Progression
Cohort 1: Time to Initiation of Cytotoxic Chemotherapy
Observed Plasma Concentrations of Niraparib
Observed Plasma Concentrations of Abiraterone
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Number of Participants With Treatment-Emergent Adverse Events by Severity
Number of Participants With Abnormalities in Laboratory Values
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility 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
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- MALE
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- 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.
- intervention Names
- Drug: Niraparib
- Drug: Abiraterone Acetate
- Drug: Prednisone
- Drug: Placebo
- label
- Cohort 1: Participants with mCRPC and HRR Gene Alteration
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Niraparib
- Drug: Abiraterone Acetate
- Drug: Prednisone
- Drug: Placebo
- label
- Cohort 2: Participants with mCRPC and No HRR Gene Alteration
- type
- EXPERIMENTAL
- description
- Participants with mCRPC will receive a new formulation of niraparib 200 mg and AA 1000 mg tablets plus prednisone 10 mg.
- intervention Names
- Drug: Prednisone
- Drug: New Formulation of Niraparib and Abiraterone Acetate (AA)
- label
- Cohort 3 (Open-label): Participants with mCRPC
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Cohort 1: Participants with mCRPC and HRR Gene Alteration
- Cohort 2: Participants with mCRPC and No HRR Gene Alteration
- description
- Participants will receive niraparib 200 mg capsules or tablets once daily.
- name
- Niraparib
- other Names
- JNJ-64091742
- type
- DRUG
- arm Group Labels
- Cohort 1: Participants with mCRPC and HRR Gene Alteration
- Cohort 2: Participants with mCRPC and No HRR Gene Alteration
- description
- Participants will receive AA 1000 mg tablets once daily.
- name
- Abiraterone Acetate
- type
- DRUG
- arm Group Labels
- Cohort 1: Participants with mCRPC and HRR Gene Alteration
- Cohort 2: Participants with mCRPC and No HRR Gene Alteration
- Cohort 3 (Open-label): Participants with mCRPC
- description
- Participants will receive prednisone 10 mg tablets daily.
- name
- Prednisone
- type
- DRUG
- arm Group Labels
- Cohort 1: Participants with mCRPC and HRR Gene Alteration
- Cohort 2: Participants with mCRPC and No HRR Gene Alteration
- description
- Participants will receive matching placebo once daily.
- name
- Placebo
- type
- DRUG
- arm Group Labels
- Cohort 3 (Open-label): Participants with mCRPC
- description
- Participants will receive a new formulation of niraparib 200 mg and AA 1000 mg tablets once daily.
- name
- New Formulation of Niraparib and Abiraterone Acetate (AA)
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- QUADRUPLE
- who Masked
- PARTICIPANT
- CARE_PROVIDER
- INVESTIGATOR
- OUTCOMES_ASSESSOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 765
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- As per BICR, rPFS is time interval from the date of randomization to radiographic progression or death, whichever occurred 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.
- measure
- Cohort 1: Radiographic Progression-Free Survival (rPFS) as Assessed by Blinded Independent Central Review (BICR)
- time Frame
- Up to 32 months
- description
- As per BICR, rPFS is time interval from the date of randomization to radiographic progression or death, whichever occurred first. Radiographic progression was determined by: (1) progression of soft tissue lesions measured by CT or MRI as per RECIST 1.1; (2) Progression of bone lesions observed by bone scan based on PCWG3 criteria. PCWG3 criteria: bone progression was confirmed by subsequent scan \>=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 \<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.
- measure
- Cohort 1 Breast Cancer Gene (BRCA) Subgroup: Radiographic Progression-Free Survival (rPFS) as Assessed by Blinded Independent Central Review (BICR)
- time Frame
- Up to 32 months
- secondary Outcomes
- measure
- Cohort 1: Overall Survival (OS)
- time Frame
- Up to 97 months
- measure
- Cohort 1: Time to Symptomatic Progression
- time Frame
- Up to 97 months
- measure
- Cohort 1: Time to Initiation of Cytotoxic Chemotherapy
- time Frame
- Up to 97 months
- measure
- Observed Plasma Concentrations of Niraparib
- time Frame
- Up to 97 months
- measure
- Observed Plasma Concentrations of Abiraterone
- time Frame
- Up to 97 months
- measure
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
- time Frame
- Up to 96 months
- measure
- Number of Participants With Treatment-Emergent Adverse Events by Severity
- time Frame
- Up to 96 months
- measure
- Number of Participants With Abnormalities in Laboratory Values
- time Frame
- Up to 96 months
Full study description
- 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.
Source references
- references
- citation
- Ye D, Saad M, Lee JY, Jung W, Pang ST, Li L, Gurney H, Attard G, Chi KN, Mundle S, Zhuo J, Singh A, Lin Y, Sandhu S. Niraparib With Abiraterone Acetate Plus Prednisone as First-Line Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer With Homologous Recombination Repair Gene Alterations: Final Analysis of the Asian Subgroup From the MAGNITUDE Study. Int J Urol. 2026 Apr;33(4):e70455. doi: 10.1111/iju.70455.
- pmid
- 42015879
- type
- DERIVED
- citation
- Rathkopf DE, Roubaud G, Chi KN, Efstathiou E, Attard G, Olmos D, Small EJ, Saad M, Castro E, Kim W, Wu D, Bertzos K, Dibaj S, Zhang J, Francis P, Smith MR. Patient-reported Outcomes for Patients with Metastatic Castration-resistant Prostate Cancer and BRCA1/2 Gene Alterations: Final Analysis from the Randomized Phase 3 MAGNITUDE Trial. Eur Urol. 2025 Oct;88(4):359-369. doi: 10.1016/j.eururo.2024.09.003. Epub 2024 Sep 23.
- pmid
- 39317633
- type
- DERIVED
- citation
- Roubaud G, Attard G, Boegemann M, Olmos D, Trevisan M, Antoni L, Pascoe K, Capone C, Van Sanden S, Hashim M, Palmer S, Chi K. Adjustment for imbalances in baseline characteristics in the MAGNITUDE phase 3 study confirms the clinical benefit of niraparib in combination with abiraterone acetate plus prednisone in patients with metastatic prostate cancer. Eur J Cancer. 2024 Sep;209:114183. doi: 10.1016/j.ejca.2024.114183. Epub 2024 Jun 17.
- pmid
- 39111209
- type
- DERIVED
- citation
- De Santis M, Breijo SM, Robinson P, Capone C, Pascoe K, Van Sanden S, Hashim M, Trevisan M, Daly C, Reitsma F, van Beekhuizen S, Ruan H, Heeg B, Verzoni E. Feasibility of Indirect Treatment Comparisons Between Niraparib Plus Abiraterone Acetate and Other First-Line Poly ADP-Ribose Polymerase Inhibitor Treatment Regimens for Patients with BRCA1/2 Mutation-Positive Metastatic Castration-Resistant Prostate Cancer. Adv Ther. 2024 Aug;41(8):3039-3058. doi: 10.1007/s12325-024-02918-6. Epub 2024 Jul 3.
- pmid
- 38958846
- type
- DERIVED
- citation
- Chi KN, Rathkopf D, Smith MR, Efstathiou E, Attard G, Olmos D, Lee JY, Small EJ, Pereira de Santana Gomes AJ, Roubaud G, Saad M, Zurawski B, Sakalo V, Mason GE, Francis P, Wang G, Wu D, Diorio B, Lopez-Gitlitz A, Sandhu S; MAGNITUDE Principal Investigators. Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2023 Jun 20;41(18):3339-3351. doi: 10.1200/JCO.22.01649. Epub 2023 Mar 23.
- pmid
- 36952634
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- Chemical Structure 14.2 BRCA -mutated Metastatic Castration-Resistant Prostate Cancer (mCRPC) The efficacy of AKEEGA was investigated in Cohort 1 of MAGNITUDE (NCT03748641), a randomized double-blind, placebo-controlled, multi-cohort, multi-center study in which 423 patients with homologous recombination repair (HRR) gene-mutated
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Preserved source evidence · Not medical advice