TriangleNCT04497844 · CITED IN SOURCE DOCUMENTS
A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC)
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
- 2026-08-20
The purpose of the study is to determine if the combination of niraparib with Abiraterone Acetate (AA) plus prednisone compared with AA plus prednisone in participants with deleterious germline or somatic Homologous Recombination Repair (HRR) gene-mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC) provides superior efficacy in improving radiographic progression-free survival (rPFS).
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
Breast Cancer Gene (BRCA) Subgroup: Radiographic Progression-free Survival (rPFS) Assessed by Investigator
HRR Effector Subgroup: Radiographic Progression-free Survival (rPFS) Assessed by Investigator
All HRR: Radiographic Progression-free Survival (rPFS) Assessed by Investigator
BRCA Subgroup: Time to Symptomatic Progression
HRR Effector Subgroup: Time to Symptomatic Progression
All HRR: Time to Symptomatic Progression
Overall Survival (OS)
Time to Subsequent Therapy
Number of Participants With Treatment-emergent Serious Adverse Events
Number of Participants With Treatment-emergent Adverse Events by Severity
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion criteria: * Pathological diagnosis of prostate adenocarcinoma * Must have appropriate deleterious homologous recombination repair (HRR) gene alteration * Metastatic disease as documented by conventional imaging with computed tomography (CT) or magnetic resonance imaging (MRI) (for soft tissue lesions) or 99mTc bone scan (for bone lesions). Participants with a single bone lesion on Technetium-99m (99mTc) bone scan with no other non-nodal metastatic disease must have confirmation of bone metastasis by CT or MRI. Participants with lymph node-only disease are not eligible * Androgen deprivation therapy (either medical or surgical castration) must have been started \>=14 days prior to randomization and participants be willing to continue androgen deprivation therapy (ADT) through the treatment phase * Other allowed prior therapy for metastatic castration-sensitive prostate cancer (mCSPC): (a) maximum of 1 course of radiation and 1 surgical intervention for symptomatic control of prostate cancer (example, uncontrolled pain, impending spinal cord compression or obstructive symptoms). Participants with radiation or surgical interventions to all known sites of metastatic disease will be excluded from trial participation. Radiation must be completed prior to randomization (b) Up to a maximum of 6 months of ADT prior to randomization; (c) Up to a maximum of 45 days of abiraterone acetate + prednisone (AA-P) prior to randomization (d) Up to a maximum of 2 weeks of ketoconazole for prostate cancer prior to randomization Exclusion criteria: * Prior treatment with a poly (adenosine diphosphate-ribose) polymerase inhibitor (PARP inhibitor) * History of adrenal dysfunction * Long-term use of systemically administered corticosteroids (greater than \[\>\] 5 milligrams \[mg\] of prednisone or the equivalent) during the study is not allowed. Short-term use (\<=4 weeks, including taper) and locally administered steroids (for example, inhaled, topical, ophthalmic, and intra-articular) are allowed, if clinically indicated * History or current diagnosis of myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML)
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- MALE
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants will receive the following in each 28-day treatment cycle: niraparib 200 milligrams (mg), abiraterone acetate (AA) 1000 mg plus prednisone 5 mg once daily.
- intervention Names
- Combination Product: Niraparib+ Abiraterone acetate fixed dose combination (FDC)
- Drug: Prednisone
- Drug: Placebo AA
- label
- Niraparib with Abiraterone Acetate plus Prednisone (AAP)
- type
- EXPERIMENTAL
- description
- Participants will receive the following in each 28-day treatment cycle: matching placebo for Niraparib along with AA 1000 mg plus prednisone 5 mg once daily.
- intervention Names
- Drug: Abiraterone acetate (AA)
- Drug: Prednisone
- Drug: Placebo FDC
- label
- AA plus Prednisone (AAP)
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Niraparib with Abiraterone Acetate plus Prednisone (AAP)
- description
- Participants will receive a FDC of Niraparib 200 mg + AA 1000 mg once daily.
- name
- Niraparib+ Abiraterone acetate fixed dose combination (FDC)
- type
- COMBINATION_PRODUCT
- arm Group Labels
- AA plus Prednisone (AAP)
- description
- Participants will receive AA 1000 mg once daily.
- name
- Abiraterone acetate (AA)
- type
- DRUG
- arm Group Labels
- AA plus Prednisone (AAP)
- Niraparib with Abiraterone Acetate plus Prednisone (AAP)
- description
- Participants will receive prednisone 5 mg once daily.
- name
- Prednisone
- type
- DRUG
- arm Group Labels
- AA plus Prednisone (AAP)
- description
- Participants will receive matching placebo for Niraparib +AA FDC once daily.
- name
- Placebo FDC
- type
- DRUG
- arm Group Labels
- Niraparib with Abiraterone Acetate plus Prednisone (AAP)
- description
- Participants will receive matching placebo for AA once daily.
- name
- Placebo AA
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- TRIPLE
- who Masked
- PARTICIPANT
- INVESTIGATOR
- OUTCOMES_ASSESSOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 696
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- rPFS: time interval from date of randomization to first date of radiographic progression as assessed by investigator or death due to any cause, whichever occurred first. rPFS was determined by: (1) progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) per response evaluation criteria in solid tumors (RECIST) 1.1; (2) progression of bone lesions observed by bone scan per prostate cancer working group 3 (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. A confirmatory scan with \>=2 new lesions indicated progression; A confirmatory scan not showing \>=2 new lesions means no progression. If Week 8 scan shows \<2 new bone lesions compared to baseline, first scan with \>=2 new lesions compared to Week 8 scan indicated progression, when confirmed by a subsequent scan \>=6 weeks later.
- measure
- Breast Cancer Gene (BRCA) Subgroup: Radiographic Progression-free Survival (rPFS) Assessed by Investigator
- time Frame
- From date of randomization (Day -3 to Day 1) up to approximately 49 months
- description
- rPFS: time interval from date of randomization to first date of radiographic progression as assessed by investigator or death due to any cause, whichever occurred first. rPFS was determined by: (1) progression of soft tissue lesions measured by CT or MRI per RECIST 1.1; (2) progression of bone lesions observed by bone scan per 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. A confirmatory scan with \>=2 new lesions indicated progression; A confirmatory scan not showing \>=2 new lesions means no progression. If Week 8 scan shows \<2 new bone lesions compared to baseline, first scan with \>=2 new lesions compared to Week 8 scan indicated progression, when confirmed by a subsequent scan \>=6 weeks later.
- measure
- HRR Effector Subgroup: Radiographic Progression-free Survival (rPFS) Assessed by Investigator
- time Frame
- From date of randomization (Day -3 to Day 1) up to approximately 49 months
- description
- rPFS: time interval from date of randomization to first date of radiographic progression as assessed by investigator or death due to any cause, whichever occurred first. rPFS was determined by: (1) progression of soft tissue lesions measured by CT or MRI per RECIST 1.1; (2) progression of bone lesions observed by bone scan per 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. A confirmatory scan with \>=2 new lesions indicated progression; A confirmatory scan not showing \>=2 new lesions means no progression. If Week 8 scan shows \<2 new bone lesions compared to baseline, first scan with \>=2 new lesions compared to Week 8 scan indicated progression, when confirmed by a subsequent scan \>=6 weeks later.
- measure
- All HRR: Radiographic Progression-free Survival (rPFS) Assessed by Investigator
- time Frame
- From date of randomization (Day -3 to Day 1) up to approximately 49 months
- secondary Outcomes
- description
- Time to symptomatic progression was defined as time from the date of randomization to the date of any of the following (whichever occurred first): (a) the use of external beam radiation therapy for skeletal or pelvic symptoms, (b) the need for tumor-related orthopedic surgical intervention, (c) other cancer-related procedures (example: nephrostomy insertion, bladder catheter insertion, external beam radiation therapy, or surgery for tumor symptoms), (d) cancer-related morbid events (that is, fracture \[symptomatic and/or pathologic\], cord compression, urinary obstructive events), (e) initiation of a new systemic anti-cancer therapy because of cancer symptoms.
- measure
- BRCA Subgroup: Time to Symptomatic Progression
- time Frame
- From date of randomization (Day -3 to Day 1) up to approximately 49 months
- description
- Time to symptomatic progression was defined as time from the date of randomization to the date of any of the following (whichever occurred first): (a) the use of external beam radiation therapy for skeletal or pelvic symptoms, (b) the need for tumor-related orthopedic surgical intervention, (c) other cancer-related procedures (example: nephrostomy insertion, bladder catheter insertion, external beam radiation therapy, or surgery for tumor symptoms), (d) cancer-related morbid events (that is, fracture \[symptomatic and/or pathologic\], cord compression, urinary obstructive events), (e) initiation of a new systemic anti-cancer therapy because of cancer symptoms.
- measure
- HRR Effector Subgroup: Time to Symptomatic Progression
- time Frame
- From date of randomization (Day -3 to Day 1) up to approximately 49 months
- description
- Time to symptomatic progression was defined as time from the date of randomization to the date of any of the following (whichever occurred first): (a) the use of external beam radiation therapy for skeletal or pelvic symptoms, (b) the need for tumor-related orthopedic surgical intervention, (c) other cancer-related procedures (example: nephrostomy insertion, bladder catheter insertion, external beam radiation therapy, or surgery for tumor symptoms), (d) cancer-related morbid events (that is, fracture \[symptomatic and/or pathologic\], cord compression, urinary obstructive events), (e) initiation of a new systemic anti-cancer therapy because of cancer symptoms.
- measure
- All HRR: Time to Symptomatic Progression
- time Frame
- From date of randomization (Day -3 to Day 1) up to approximately 49 months
- measure
- Overall Survival (OS)
- time Frame
- From date of randomization (Day -3 to Day 1) up to 83 months
- measure
- Time to Subsequent Therapy
- time Frame
- From date of randomization (Day -3 to Day 1) up to 83 months
- measure
- Number of Participants With Treatment-emergent Serious Adverse Events
- time Frame
- From Cycle 1 Day 1 up to 83 months
- measure
- Number of Participants With Treatment-emergent Adverse Events by Severity
- time Frame
- From Cycle 1 Day 1 up to 83 months
Full study description
- brief Summary
- The purpose of the study is to determine if the combination of niraparib with Abiraterone Acetate (AA) plus prednisone compared with AA plus prednisone in participants with deleterious germline or somatic Homologous Recombination Repair (HRR) gene-mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC) provides superior efficacy in improving radiographic progression-free survival (rPFS).
- detailed Description
- Prostate cancer is a heterogenous disease and recent genomic analyses have highlighted specific germline and somatic mutations and alternative driver growth signaling pathways in patients with metastatic disease. Abiraterone acetate plus prednisone (AAP) is an established standard of care for the treatment of participants with mCSPC and is included in widely accepted clinical treatment guidelines. Niraparib in combination with AAP has been approved for the treatment of BRCA-mutated Metastatic Castration-Resistant Prostate Cancer (mCRPC). Niraparib is an investigational agent in the Metastatic Castration-Sensitive Prostate Cancer (mCSPC) population. Whether the addition of niraparib to the AAP standard of care may improve initial disease control and long-term outcomes compared with AAP alone in a biomarker selected mCSPC population is being evaluated on this trial. The study will consist of 4 phases; a Prescreening Phase for biomarker evaluation for eligibility only, a Screening Phase, a Treatment Phase, and a Follow-up Phase. Efficacy evaluations include the following: tumor measurements by computed tomography (CT), magnetic resonance imaging (MRI; abdomen, chest, and pelvis), Technetium-99m (99mTc) bone scans, serum prostate sensitive antigen (PSA) evaluations, and patient reported outcomes (PROs). Safety evaluations include incidence of adverse events and clinical laboratory parameters.
Source references
- references
- citation
- Attard G, Agarwal N, Graff JN, Sandhu S, Efstathiou E, Ozguroglu M, Pereira de Santana Gomes AJ, Vianna K, Luo H, Gotto GT, Cheng HH, Kim W, Varela CR, Schaeffer D, Kramer K, Li S, Baron B, Shen F, Mundle SD, McCarthy SA, Olmos D, Chi KN, Rathkopf DE. Niraparib and abiraterone acetate plus prednisone for HRR-deficient metastatic castration-sensitive prostate cancer: a randomized phase 3 trial. Nat Med. 2025 Dec;31(12):4109-4118. doi: 10.1038/s41591-025-03961-8. Epub 2025 Oct 7.
- pmid
- 41057655
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- 14 CLINICAL STUDIES 14.1 BRCA2 -mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC) The efficacy of AKEEGA was investigated in AMPLITUDE (NCT04497844), a randomized double-blind, placebo-controlled, multi-cohort, multi-center study in which 696 patients with homologous recombination repair (HRR) gene-mutated
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- ;<a href="https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm">Drugs@FDA</a>.</p><h2>Efficacy and Safety</h2><p>Efficacy was evaluated in AMPLITUDE (NCT04497844), a randomized, double-blind trial in 696 patients with homologous recombination repair (HRR) gene-mutated (HRRm) mCSPC. Patients were randomized (1:1) to rece
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Preserved source evidence · Not medical advice