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A Phase 3 Study of Niraparib in Combination with Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Patients with Metastatic Prostate Cancer

Phase 1
Conditions
Metastatic Prostate Cancer
MedDRA version: 21.1Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2017-003364-12-IT
Lead Sponsor
JANSSEN CILAG INTERNATIONAL NV
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
Male
Target Recruitment
1100
Inclusion Criteria

1. Criterion modified per Amendment 3
1.1 Criterion modified per Amendment 4
1.2 HRR gene alteration status (as identified by the sponsor's required assays or local testing for HRR gene alteration) as follows:
a. Cohort 1: positive for HRR gene alteration
b. Cohort 2: not positive for HRR gene alteration (ie, no HRR gene alteration)
c. Cohort 3
2. Metastatic disease documented by radiographic imaging
4. Able to continue GnRHa during the study if not surgically castrate
5. ECOG PS Grade of 0 or 1
6 Score of <=3 on the Brief Pain Inventory-Short Form (BPI-SF) Question #3 (worst pain in last 24 hours).
7. Adequate clinical laboratory values at Screening
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 260
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 840

Exclusion Criteria

1. Prior treatment with a PARP inhibitor
2. No prior systemic therapy for mCRPC except for GnRHa and limited AA-P
4. Symptomatic brain metastases
5. History or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
6. Other prior malignancy =2 years prior to randomization, or malignancy that currently requires active systemic therapy
7. Severe or unstable angina, myocardial infarction or ischemia requiring coronary artery bypass graft or stent within the previous 6 months, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g. adequate cardiac function), or clinically significant ventricular arrhythmias within 6 months prior to randomization or New York Heart Association (NYHA) Class II to IV heart disease
8. Presence of uncontrolled hypertension
9. Current evidence of any of the following:
a. Any medical condition that would make prednisone use contraindicated
b. Any chronic medical condition requiring a higher equivalent dose of corticosteroid than 10 mg prednisone (or equivalent) per day
11. History of adrenal dysfunction
13. Subjects who are receiving opioid analgesics at the time of screening
14. Active human immunodeficiency virus (HIV) infection

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To evaluate the effectiveness of niraparib plus AA-P compared to AA-P plus placebo.;Secondary Objective: * To assess the clinical benefit of niraparib plus AA-P compared to AA-P plus placebo<br>* To characterize the safety profile of niraparib when given with AA-P compared to AA-P with placebo;Primary end point(s): Radiographic progression-free survival (rPFS);Timepoint(s) of evaluation of this end point: While on study treatment, radiographic imaging will be performed at Cycle 3 Day 1, Cycle 5 Day 1, Cycle 7 Day 1, and then every 12 weeks
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): * OS<br>* Time to symptomatic progression<br>* Time to initiation of cytotoxic chemotherapy<br>* Observed plasma concentrations of niraparib and abiraterone and estimated population PK and exposure parameters for niraparib <br>* Incidence and severity of AEs<br>* Clinical laboratory test results;Timepoint(s) of evaluation of this end point: Assessments of the secondary endpoints are variable but carried out on a regular basis from C1D1 through the follow up as described in the endpoint requirements
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