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)

Janssen (J&J Innovative Medicine)

Status and phase: Active, not recruiting; Phase 3

Conditions: Castration-Resistant Prostatic Cancer

Treatments: Drug: Prednisone; Drug: New Formulation of Niraparib and Abiraterone Acetate (AA); Drug: Niraparib; Drug: Abiraterone Acetate; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03748641

2023-503254-12-00 (Registry Identifier)

CR108534

2017-003364-12 (EudraCT Number)

64091742PCR3001 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 765 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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765 participants in 3 patient groups

Cohort 1: Participants with mCRPC and HRR Gene Alteration

Experimental group

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.

Treatment:

Drug: Placebo

Drug: Abiraterone Acetate

Drug: Niraparib

Drug: Prednisone

Cohort 2: Participants with mCRPC and No HRR Gene Alteration

Experimental group

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.

Treatment:

Drug: Placebo

Drug: Abiraterone Acetate

Drug: Niraparib

Drug: Prednisone

Cohort 3 (Open-label): Participants with mCRPC

Experimental group

Description:

Participants with mCRPC will receive a new formulation of niraparib 200 mg and AA 1000 mg tablets plus prednisone 10 mg.

Treatment:

Drug: New Formulation of Niraparib and Abiraterone Acetate (AA)

Drug: Prednisone