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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)

NCT04497844

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).

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

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

  • Castration-Resistant Prostatic Cancer

Interventions

DrugSynonymsArms
NiraparibNiraparib with Abiraterone Acetate plus Prednisone (AA-P)
Abiraterone acetate (AA)Niraparib with Abiraterone Acetate plus Prednisone (AA-P)
PrednisoneAA plus Prednisone (AA-P)
Placebo for NiraparibAA 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 with 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

NameTypeDescriptionInterventions
Niraparib with Abiraterone Acetate plus Prednisone (AA-P)ExperimentalParticipants 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)ExperimentalParticipants 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

          -  Willing to provide an archival tumor tissue sample or a fresh tumor tissue sample. If
             germline positive for deleterious germline or somatic homologous recombination repair
             (HRR) gene mutations, an archived or fresh tumor tissue sample is not required

          -  Metastatic disease documented by greater than or equal to (>=) 1 bone lesion(s) on
             Technetium-99m (99mTc) bone scan. Participants with a single bone lesion must have
             confirmation of bone metastasis by computed tomography (CT) or magnetic resonance
             imaging (MRI)

          -  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. Participants who start a gonadotropin-releasing hormone (GnRH) agonist less
             than or equal to (<=) 28 days prior to randomization will be required to take a
             first-generation anti-androgen for >=14 days prior to randomization. The anti-androgen
             must be discontinued prior to randomization

          -  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:

          -  Pathological finding consistent with small cell ductal or neuroendocrine carcinoma of
             the prostate

          -  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:Not yet recruiting
Lead Sponsor:Janssen Research & Development, LLC

Last Updated

July 31, 2020