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A Study of Niraparib Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer

NCT ID: NCT03431350

Last Updated: 2025-11-12

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

136 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-03-02

Study Completion Date

2025-12-31

Brief Summary

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The purpose of this study is to: a) establish the recommended phase 2 dose (RP2D) and to evaluate the antitumor activity and safety of niraparib combination therapies (Combinations 1 and 2) and b) to determine the relative bioavailability of niraparib and abiraterone acetate (AA) in combination (Combination 3) in participants with metastatic castration-resistant prostate cancer (mCRPC).

Detailed Description

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This multicenter study will evaluate safety and efficacy of niraparib in combination with other anti-cancer agents. Combination 1 will combine niraparib with the anti-programmed cell death protein (PD)-1 monoclonal antibody cetrelimab, in participants with mCRPC. Combination 1 has 2 parts: in Part 1 (dose selection), participants will be enrolled to establish RP2D doses of niraparib and cetrelimab; and Part 2 (dose expansion) will evaluate the combination therapy in an expanded number of participants into 2 cohorts (biomarker positive or biomarker negative). Combination 2 will combine niraparib with abiraterone acetate plus prednisone (AA-P) in mCRPC participants with DNA-repair gene defects (DRD). Combination 3 will evaluate the relative bioavailability (BA) of niraparib and AA in combination. In a pharmacokinetics (PK) assessment phase, niraparib and AA will be administered, and in an extension phase, niraparib and AA-P will be administered. Combinations 1 and 2 will have 5 phases: A Pre-screening Phase, a Screening Phase, a Treatment Phase, a Follow-up Phase, and a Long-term Extension (LTE) Phase; Combination 3 has 3 phases: A Screening Phase, A PK Assessment Phase, an Extension Phase (including LTE phase). Study evaluations will include efficacy, PK, PK/pharmacodynamics, biomarkers, safety and tolerability.

Conditions

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Prostatic Neoplasms, Castration-Resistant

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Combination 1:Dose Selection: Niraparib + cetrelimab (Part 1)

Dose regimen 1: The participants will receive niraparib 200 milligram (mg) orally once daily in combination with cetrelimab 240 mg intravenously (IV) once every 2 weeks. Dose regimen 2: The participants will receive niraparib 200 mg orally once daily in combination with cetrelimab 480 mg IV once every 4 weeks in 28-day treatment cycles until disease progression, unacceptable toxicity, death, or the sponsor terminates the study. The safety evaluation team (SET) will determine if an additional cohort is necessary, based on the data from dose regimens 1 and 2. Participants in the Treatment Phase of this combination will be offered the option to enter the Long-term Extension Phase of the study.

Group Type EXPERIMENTAL

Niraparib 200 mg

Intervention Type DRUG

Participants will receive niraparib 200 mg orally.

Cetrelimab 240 mg

Intervention Type DRUG

Participants will receive cetrelimab 240 mg IV every 2 weeks.

Cetrelimab 480 mg

Intervention Type DRUG

Participants will receive cetrelimab 480 mg IV every 4 weeks.

Combination 1:Dose Expansion: Niraparib + cetrelimab (Part 2)

Participants will be assigned to either Cohort 1A (Biomarker \[BM\] positive \[+\]) or Cohort 1B (BM negative \[-\]) and will receive established RP2D of cetrelimab and niraparib, in Part 2 until disease progression, unacceptable toxicity, death, or the sponsor terminates the study. A futility analysis will be performed for the Cohort 1B after 10 BM- participants are enrolled in Part 2. This cohort will be closed if the response is less than predetermined response rate as outlined in the protocol. Participants in the Treatment Phase of this combination will be offered the option to enter the Long-term Extension Phase of the study.

Group Type EXPERIMENTAL

Niraparib 200 mg

Intervention Type DRUG

Participants will receive niraparib 200 mg orally.

Cetrelimab 480 mg

Intervention Type DRUG

Participants will receive cetrelimab 480 mg IV every 4 weeks.

Combination 2: Dose Expansion: Niraparib + AA-P (Part 2)

Participants will be assigned to one of 4 cohorts based on biomarker status - Cohort 2A (BRCA biallelic loss), 2B (other DRD biallelic loss), 2C (BRCA monoallelic loss), or 2D (other DRD monoallelic loss), and will receive niraparib 200 mg once daily in combination with abiraterone acetate 1000 mg (4\*250 mg) plus 10 mg prednisone (5 mg twice daily) throughout treatment phase. Participants in the Treatment Phase of this combination will be offered the option to enter the Long-term Extension Phase of the study.

Group Type EXPERIMENTAL

Niraparib 200 mg

Intervention Type DRUG

Participants will receive niraparib 200 mg orally.

Abiraterone acetate 1000 mg

Intervention Type DRUG

Participants will receive AA 1000 mg orally.

Prednisone 5 mg

Intervention Type DRUG

Participants will receive prednisone 5 mg orally.

Combination 3: Niraparib + AA-P

Participants will be assigned to one of three cohorts to receive AA-P with or without niraparib. Participants in the Treatment Phase of this combination will be offered the option to enter the Long-term Extension Phase of the study.

Group Type EXPERIMENTAL

Niraparib 200 mg

Intervention Type DRUG

Participants will receive niraparib 200 mg orally.

Abiraterone acetate 1000 mg

Intervention Type DRUG

Participants will receive AA 1000 mg orally.

Prednisone 5 mg

Intervention Type DRUG

Participants will receive prednisone 5 mg orally.

Interventions

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Niraparib 200 mg

Participants will receive niraparib 200 mg orally.

Intervention Type DRUG

Cetrelimab 240 mg

Participants will receive cetrelimab 240 mg IV every 2 weeks.

Intervention Type DRUG

Cetrelimab 480 mg

Participants will receive cetrelimab 480 mg IV every 4 weeks.

Intervention Type DRUG

Abiraterone acetate 1000 mg

Participants will receive AA 1000 mg orally.

Intervention Type DRUG

Prednisone 5 mg

Participants will receive prednisone 5 mg orally.

Intervention Type DRUG

Other Intervention Names

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JNJ-63723283 JNJ-63723283

Eligibility Criteria

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Inclusion Criteria

* Diagnosed with mCRPC, who in the opinion of the investigator may benefit from treatment in Combination 3 of this study
* Able to continue gonadotropin releasing hormone analogue (GnRHa) therapy during the study if not surgically castrate (that is, subjects who has not undergone bilateral orchiectomy).
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) of less than or equal to (\<=) 1
* Toxicity associated with prior chemotherapy or radiotherapy has resolved to Grade \<= 1 (except alopecia or Grade \<= 2 neuropathy) at screening
* Participant must agree not to donate sperm while on study treatment, and for 3 months following the last dose of study treatment

Exclusion Criteria

* History or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
* Active malignancies (that is, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are: non-muscle invasive bladder cancer; skin cancer (non-melanoma or melanoma); breast cancer; malignancy that is considered cured with minimal risk of recurrence
* Active infection requiring systemic therapy
* Allergies, hypersensitivity, or intolerance to niraparib or the corresponding excipients

Combination 3:

* Symptomatic brain metastases
* Prior disease progression during combination treatment with AA and poly (adenosine diphosphate \[ADP\]-ribose) polymerase inhibitor (PARPi). Prior discontinuation of treatment with AA or PARPi due to AA- or PARPi-related toxicity
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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Urological Associates of Southern Arizona, P.C.

Tucson, Arizona, United States

Site Status

The Urology Center of Colorado

Denver, Colorado, United States

Site Status

Mayo Clinic - Division Of Hematology/oncology

Jacksonville, Florida, United States

Site Status

First Urology, PSC

Jeffersonville, Indiana, United States

Site Status

Chesapeake Urology Research Associates

Towson, Maryland, United States

Site Status

Michigan Institute of Urology

Troy, Michigan, United States

Site Status

New York Oncology Hematology

Albany, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

Harrison, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center (UPMC)

Pittsburgh, Pennsylvania, United States

Site Status

MUSC-Hollings Cancer Center

Charleston, South Carolina, United States

Site Status

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Site Status

Urology Associates

Nashville, Tennessee, United States

Site Status

Houston Metro Urology

Houston, Texas, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Utah Cancer Specialists

Salt Lake City, Utah, United States

Site Status

Urology of Virginia, PLCC

Virginia Beach, Virginia, United States

Site Status

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States

Site Status

OLV Ziekenhuis Aalst

Aalst, , Belgium

Site Status

ZNA Middelheim

Antwerp, , Belgium

Site Status

ULB Hôpital Erasme

Brussels, , Belgium

Site Status

Universitair Ziekenhuis Gent

Ghent, , Belgium

Site Status

Az Groeninge

Kortrijk, , Belgium

Site Status

Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman

Liège, , Belgium

Site Status

Southern Alberta Institute of Urology / Prostate Cancer Centre

Calgary, Alberta, Canada

Site Status

British Columbia Cancer Agency

Vancouver, British Columbia, Canada

Site Status

Princess Margaret Cancer Centre University Health Network

Toronto, Ontario, Canada

Site Status

Centre de Recherche du CHUM

Montreal, Quebec, Canada

Site Status

Asaf Harofe Medical Center

Beer Yaakov, , Israel

Site Status

Soroka Hospital

Beersheba, , Israel

Site Status

Rambam Medical Center

Haifa, , Israel

Site Status

Rabin Medical Center

Petah Tikva, , Israel

Site Status

Sheba Medical Center Tel Hashomer

Ramat Gan, , Israel

Site Status

Azienda Ospedaliera Universitaria Careggi di Firenze

Florence, , Italy

Site Status

Azienda Ospedaliera ''Vito Fazzi''

Lecce, , Italy

Site Status

UOC Oncologia Ospedale Provinciale di Macerata

Macerata, , Italy

Site Status

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Site Status

IRCCS-Fondazione Pascale

Napoli, , Italy

Site Status

Hosp. de La Santa Creu I Sant Pau

Barcelona, , Spain

Site Status

Hospital Vall D'Hebron

Barcelona, , Spain

Site Status

Hosp. Univ. de La Princesa

Madrid, , Spain

Site Status

Hosp Univ Fund Jimenez Diaz

Madrid, , Spain

Site Status

Hosp Univ Hm Sanchinarro

Madrid, , Spain

Site Status

Hosp Virgen de La Victoria

Málaga, , Spain

Site Status

Royal United Hospital

Bath, , United Kingdom

Site Status

University College London Hospitals

London, , United Kingdom

Site Status

Southampton General Hospital

Southampton, , United Kingdom

Site Status

The Royal Marsden NHS Trust Sutton

Sutton, , United Kingdom

Site Status

Royal Cornwall Hospitals NHS Trust - Royal Cornwall Hospital

Truro, , United Kingdom

Site Status

Countries

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France United States Belgium Canada Israel Italy Spain United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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64091742PCR2002

Identifier Type: OTHER

Identifier Source: secondary_id

2017-003552-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR108406

Identifier Type: -

Identifier Source: org_study_id