Description:
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.
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
- Castration-Resistant Prostatic Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| Niraparib | JNJ-64091742 | Cohort 1: Participants with mCRPC and HRR Gene Alteration |
| Abiraterone Acetate | | Cohort 1: Participants with mCRPC and HRR Gene Alteration |
| Prednisone | | Cohort 1: Participants with mCRPC and HRR Gene Alteration |
| Placebo | | Cohort 1: Participants with mCRPC and HRR Gene Alteration |
| New Formulation of Niraparib and Abiraterone Acetate (AA) | | Cohort 3 (Open-label): Participants with mCRPC |
Purpose
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.
Detailed Description
This study will assess efficacy and safety of niraparib in combination with AAP for the
treatment of participants with metastatic castration resistant 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
17 alpha-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 anomalies are identified in approximately 15 percent (%) to 20% of tumors. The
study will consist of 5 phases: a prescreening phase for biomarker evaluation only, a
screening phase, a treatment phase, a follow up phase, and an extension phase (either
open-label extension [OLE] or long-term extension [LTE]). During the prescreening phase
participants will be evaluated for homologous recombination repair (HRR) gene alteration
status 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 66 months.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Cohort 1: Participants with mCRPC and HRR Gene Alteration | Experimental | 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. | - Niraparib
- Abiraterone Acetate
- Prednisone
- Placebo
|
| Cohort 2: Participants with mCRPC and No HRR Gene Alteration | Experimental | 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. | - Niraparib
- Abiraterone Acetate
- Prednisone
- Placebo
|
| Cohort 3 (Open-label): Participants with mCRPC | Experimental | Participants with mCRPC will receive a new formulation of niraparib 200 mg and AA 1000 mg tablets plus prednisone 10 mg. | - Prednisone
- New Formulation of Niraparib and Abiraterone Acetate (AA)
|
Eligibility Criteria
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Male |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Cohort 1 and 3: Radiographic Progression Free Survival (rPFS) |
| Time Frame: | Up to 28 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. Participants whose confirmatory scan shows >=2 new lesions will be considered to have bone scan progression and participants whose confirmatory scans 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: | Cohort 1: Overall survival (OS) |
| Time Frame: | Up to 66 months |
| Safety Issue: | |
| Description: | OS is defined as the time from date of randomization to date of death from any cause. |
| Measure: | Cohort 1: Time to Symptomatic Progression |
| Time Frame: | Up to 28 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: | Cohort 1: Time to Initiation of Cytotoxic Chemotherapy |
| Time Frame: | Up to 28 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: | Cohort 1: 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: | Cohort 1: 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: | Cohort 1: Number of Participants with Treatment-Emergent Adverse events (TEAEs) |
| Time Frame: | Up to 66 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: | Cohort 1: Number of Participants with Treatment-Emergent Adverse events by Severity |
| Time Frame: | Up to 66 months |
| Safety Issue: | |
| Description: | Adverse event is any untoward medical occurrence in clinical study participant administered a medicinal (investigational or non-investigational) product. AE does not necessarily have 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 and 5) Death. |
| Measure: | Cohort 1: Number of Participants with Laboratory Abnormalities as Measure of Safety |
| Time Frame: | Up to 66 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 |
Last Updated
August 20, 2021
