Description:
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).
Title
- Brief Title: 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)
- 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 for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC)
Clinical Trial IDs
- ORG STUDY ID:
CR108852
- SECONDARY ID:
2020-002209-25
- SECONDARY ID:
67652000PCR3002
- NCT ID:
NCT04497844
Conditions
- Metastatic Castrate Sensitive Prostate Cancer
Interventions
Drug | Synonyms | Arms |
---|
Niraparib | | Niraparib with Abiraterone Acetate plus Prednisone (AA-P) |
Abiraterone acetate (AA) | | Niraparib with Abiraterone Acetate plus Prednisone (AA-P) |
Prednisone | | AA plus Prednisone (AA-P) |
Placebo for Niraparib | | AA plus Prednisone (AA-P) |
Purpose
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 (AA-P) is an
established standard of care for the treatment of participants with mCSPC and is included in
widely accepted clinical treatment guidelines. Niraparib is an investigational agent in the
castration-sensitive cancer population and has been approved for the treatment of ovarian
cancer. The addition of niraparib to the AA-P backbone regimen may improve initial disease
control and long-term outcomes compared with AA-P alone in a biomarker selected population.
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Niraparib with Abiraterone Acetate plus Prednisone (AA-P) | Experimental | 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. | - Niraparib
- Abiraterone acetate (AA)
- Prednisone
|
AA plus Prednisone (AA-P) | Experimental | 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. | - Prednisone
- Placebo for Niraparib
|
Eligibility Criteria
Inclusion criteria:
- Diagnosis of prostate adenocarcinoma
- Must have appropriate deleterious homologous recombination repair (HRR) gene
alteration
- Metastatic disease as documented by at least one bone lesion
- Androgen deprivation therapy (either medical or surgical castration) must have been
started >=14 days prior to randomization and willing to continue through the treatment
phase.
- Other allowed prior therapy for metastatic castration-sensitive prostate cancer
(mCSPC): (a) maximum of 1 course of radiation or surgical intervention to manage
symptoms of prostate cancer. Radiation with curative intent is not allowed. Radiation
must be completed prior to randomization (b) <= 6 months of androgen deprivation
therapy (ADT) prior to randomization; and (c) 30 days of abiraterone acetate +
prednisone (AA-P) allowed if required
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)
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Male |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Radiographic Progression-free Survival (rPFS) |
Time Frame: | Up to 47 months |
Safety Issue: | |
Description: | rPFS is defined as time from randomization date to date of radiographic progression or death, whichever occurs first. Radiographic progression will be evaluated by Prostate Cancer Working Group 3 (PCWG3) criteria. |
Secondary Outcome Measures
Measure: | Overall Survival (OS) |
Time Frame: | Up to 78 months |
Safety Issue: | |
Description: | OS is defined as the time from date of randomization to date of death from any cause. |
Measure: | Symptomatic Progression-free Survival |
Time Frame: | Up to 47 months |
Safety Issue: | |
Description: | Symptomatic progression free survival is defined as time from the date of randomization to the onset of symptoms consistent with progression of metastatic prostate cancer. |
Measure: | Time to Subsequent Therapy |
Time Frame: | Up to 47 months |
Safety Issue: | |
Description: | Time to Subsequent Therapy is defined as the time from date of randomization to the date of initiation of subsequent therapy for prostate cancer. |
Measure: | Number of Participants with Adverse Events as a Measure of Safety and Tolerability |
Time Frame: | Up to 78 months |
Safety Issue: | |
Description: | An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. AE does not necessarily have a causal relationship with intervention. |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Janssen Research & Development, LLC |
Last Updated
August 20, 2021