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A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Participants With Metastatic Prostate Cancer

NCT03748641

Description:

The purpose of this study is to evaluate the effectiveness of niraparib in combination with abiraterone acetate and prednisone (AA-P) compared to AA-P plus placebo.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

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 Treatment of Participants With Metastatic Prostate Cancer
  • 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 in Subjects With Metastatic Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: CR108534
  • SECONDARY ID: 2017-003364-12
  • SECONDARY ID: 64091742PCR3001
  • NCT ID: NCT03748641

Conditions

  • Metastatic Prostate Cancer

Interventions

DrugSynonymsArms
NiraparibJNJ-64091742Niraparib + Abiraterone Acetate-Prednisone (AA-P)
Abiraterone AcetateNiraparib + Abiraterone Acetate-Prednisone (AA-P)
PrednisoneNiraparib + Abiraterone Acetate-Prednisone (AA-P)
PlaceboPlacebo + AA-P

Purpose

The purpose of this study is to evaluate the effectiveness of niraparib in combination with abiraterone acetate and prednisone (AA-P) compared to AA-P plus placebo.

Detailed Description

      This study will assess efficacy and safety of niraparib in combination with AA-P for the
      treatment of participants with metastatic prostate cancer. Niraparib is an orally available,
      highly selective poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, with
      potent activity against PARP-1 and PARP-2 deoxyribonucleic acid (DNA)-repair polymerases. AA
      is a pro-drug of abiraterone and selectively inhibits the enzyme 17α-hydroxylase/C17,20-lyase
      (CYP17), which is found in the testes and adrenals, as well as in prostate tissues and
      tumors. In participants with metastatic prostate cancer, DNA-repair gene defects (DRD) are
      identified in approximately 15 percent (%) to 20% of tumors. The study will consist of 4
      phases: a prescreening phase for biomarker evaluation only, a screening phase, a double-blind
      treatment phase, and a follow up phase. During the prescreening phase participants will be
      evaluated for DRD and then will be assigned to one of the 2 cohorts based on their biomarker
      status. Treatment will be administered daily and is planned to be continuous until disease
      progression, unacceptable toxicity, death, or the sponsor terminates the study. Efficacy,
      pharmacokinetics, biomarkers, participants reported outcomes and safety will be assessed. The
      total duration of study will be approximately up to 73 months.
    

Trial Arms

NameTypeDescriptionInterventions
Niraparib + Abiraterone Acetate-Prednisone (AA-P)ExperimentalParticipants will receive oral administration of niraparib 200 milligram (mg) (2 capsules of 100 mg each) in combination with abiraterone acetate (AA) 1000 mg (4 tablets of 250 mg each) tablets and prednisone 10 mg (2 tablets of 5 mg each) tablets daily in each cycle (each cycle of 28 days).
  • Niraparib
  • Abiraterone Acetate
  • Prednisone
Placebo + AA-PActive ComparatorParticipants will receive oral administration of matching placebo capsules in combination with AA 1000 mg (4 tablets of 250 mg each) tablets and prednisone 10 mg (2 tablets of 5 mg each) tablets daily in each cycle (each cycle of 28 days).
  • Abiraterone Acetate
  • Prednisone
  • Placebo

Eligibility Criteria

        Inclusion Criteria:

          -  Deoxyribonucleic acid (DNA)-repair gene defects (DRD) status (as identified by the
             sponsor's required assays) as follows:

               1. Cohort 1: positive for DRD

               2. Cohort 2: not positive for DRD (i.e. No DRD)

          -  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 [AA-P] prior to randomization) in the
             metastatic castration-sensitive prostate cancer (mCRPC) setting; or AA-P 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
      
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:Approximately 40 months
Safety Issue:
Description:As per blinded independent central review, 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) as follows: progression of soft tissue lesions measured by computed tomography/magnetic resonance imaging as per response evaluation criteria in solid tumors (RECIST) 1.1; progression by bone lesions observed by bone scan and based on PCWG3. As per criteria, any bone progression must be confirmed by a subsequent scan greater than or equal to (>=) 6 weeks later. Week 8 scan will be baseline to which all subsequent scans will be compared to determine progression. Bone progression is defined as one of the following: participants whose confirmatory scan shows >=2 new lesions will be considered to have bone scan progression and who did not show >= 2 new lesions will not be considered to have bone scan progression when compared to Week 8 scan.

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:Approximately up to 73 months
Safety Issue:
Description:OS is defined as the time from date of randomization to date of death from any cause.
Measure:Time to Symptomatic Progression
Time Frame:Up to 40 months
Safety Issue:
Description:Time to symptomatic progression is defined as the need to initiate/record any of the following; a. the use of external beam radiation therapy (EBRT) for skeletal symptoms; b. the need for tumor-related orthopedic surgical intervention; c. other cancer-related procedures (for example: nephrostomy insertion, bladder catheter insertion, EBRT, or surgery for tumor symptoms other than skeletal); d. cancer-related morbid events (for example: fracture [symptomatic and/or pathologic, cord compression, urinary obstructive events); e. initiation of new systemic anti-cancer therapy because of cancer pain.
Measure:Time to Initiation of Cytotoxic Chemotherapy
Time Frame:Up to 40 months
Safety Issue:
Description:Time to initiation of cytotoxic chemotherapy is defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy for prostate cancer.
Measure:Observed Plasma Concentrations of Niraparib
Time Frame:Cycle 2 to 7; Each Cycle is of 28 days (Up to 7 months)
Safety Issue:
Description:Observed plasma concentrations of niraparib with descriptive statistics will be reported.
Measure:Observed Trough Plasma Concentrations of Abiraterone
Time Frame:Cycles 2 and 3; Each Cycle is of 28 days (Up to 3 months)
Safety Issue:
Description:Observed trough plasma concentrations of abiraterone with descriptive statistics will be reported.
Measure:Number of Participants with Treatment-Emergent Adverse events (TEAEs)
Time Frame:Approximately up to 73 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. AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal product. TEAEs are those events that occur or worsen on or after first dose of study drug through 30 days after last dose of study drug.
Measure:Number of Participants with Treatment-Emergent Adverse events by Severity
Time Frame:Approximately up to 73 months
Safety Issue:
Description:An adverse event 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. AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal product. TEAEs are those events that occur or worsen on or after first dose of study drug through 30 days after last dose of study drug. Severity criteria includes grades:1) Mild: easily tolerated, causing minimal discomfort and no interference with everyday activities 2) Moderate: sufficient discomfort to cause interference with normal activity 3) Severe: extreme distress, significant impairment of functioning/incapacitation. Prevents everyday activities 4) Life-threatening: urgent intervention indicated 5) Death
Measure:Number of Participants with Laboratory Abnormalities as Measure of Safety
Time Frame:Approximately up to 73 months
Safety Issue:
Description:Number of participants with laboratory abnormalities (hematology, serum chemistry and liver function test) will be determined.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Janssen Research & Development, LLC

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