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

NCT03431350 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 3 other identifiers: CR10840664091742PCR20022017-003552-23
• Study Type: interventional
• Target: 136
• Locations: 7 countries
• Sites: 50

Brief Summary

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).

Conditions

Prostatic Neoplasms, Castration-Resistant

Outcome Measures

Primary Outcomes (11)

• Combination 1: Part 1: Number of Participants With Specified Toxicity

  Number of participants with specified toxicity during Cycle 1 was reported. Only toxicities that occurred during safety evaluation period(defined as first 28 days of treatment-Cycle 1 of Part 1) was used for analysis of specified toxicities and for dose reduction decisions. Toxicities were graded for severity as per NCI-CTCAE, version 4.03. Safety evaluation criteria were: Any Grade(G) \>=3 non-hematological toxicity without anorexia, or constipation, fatigue improved to G\<=2 in \<7 days, vomiting and diarrhea resolved in \<=3 days, laboratory abnormalities with hospitalization, tumor flare improved to G\<=2 in \<=7 days, elevation in AST/ALT for \<=7 days and G3 hypertension controlled by medical therapy; any treatment-related(TR)G4 or G\>=3 thrombocytopenia required platelet transfusion; Any TR G4 neutropenia \>=7 days or G3 or 4 neutropenia with infection/fever \>38.5 degrees Celsius; Any TR SAE or intolerable toxicity.

  Cycle 1 (28 days)

• Combination 1: Part 2: Objective Response Rate (ORR)

  ORR of soft tissue (visceral or nodal disease) was defined as percentage of participants with measurable disease who achieved a best response of either complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with no evidence of bone progression according to prostate cancer working group 3 (PCWG3) criteria.

  Up to 37 months

• Combination 2: Composite Response Rate (RR)

  Composite response rate was defined as the percentage of participants who had a composite response which is defined as one of the following PCWG3 criteria: Objective response (percentage of participants with measurable disease who achieved a best response of either CR or PR as assessed by RECIST 1.1 with no evidence of bone progression according to PCWG3 criteria) (confirmed per RECIST 1.1), or; circulating tumor cells (CTC) response: defined as CTC=0 per 7.5 milliliters (mL) of blood at 8 weeks for participants who had CTC greater than or equal to (\>=) 1 at baseline or CTC less than (\<) 5 per 7.5 mL with CTC \>=5 at baseline, confirmed by a second consecutive value obtained 4 or more weeks later, or prostate-specific antigen (PSA) declined of \>=50 percentage (%), measured twice 3 to 4 weeks apart. This outcome measure was analyzed for specified arms only as pre-planned in the protocol.

  Up to 31 months

• Combination 1: Part 2: Number of Participants With Adverse Events (AEs)

  AE was defined as an any untoward medical occurrence in a clinical study subject administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment.

  Up to 37 months

• Combination 2: Number of Participants With Adverse Events (AEs)

  AE was defined as an any untoward medical occurrence in a clinical study subject administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment.

  Up to 31 months

• Combination 1: Part 2: Number of Participants With Adverse Events (AEs) of Grade >=3 Severity

  AE was defined as an any untoward medical occurrence in a clinical study subject administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An assessment of severity grade was made using the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) as Grade 1 (mild): awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering with everyday activities; Grade 2 (moderate): sufficient discomfort is present to cause interference with normal activity; Grade 3 (severe): extreme distress, causing significant impairment of functioning or incapacitation, prevents normal everyday activities; Grade 4 (Life-threatening): urgent intervention indicated; and Grade 5 (death).

  Up to 37 months

• Combination 2: Number of Participants With Adverse Events (AEs) of Grade >=3 Severity

  AE was defined as an any untoward medical occurrence in a clinical study subject administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An assessment of severity grade was made using the NCI-CTCAE as Grade 1 (mild): awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering with everyday activities; Grade 2 (moderate): sufficient discomfort is present to cause interference with normal activity; Grade 3 (severe): extreme distress, causing significant impairment of functioning or incapacitation, prevents normal everyday activities; Grade 4 (Life-threatening): urgent intervention indicated; and Grade 5 (death).

  Up to 31 months

• Combination 3: Maximum Observed Plasma Concentration (Cmax) of Niraparib and Abiraterone Acetate After a Single Dose

  Cmax is defined as maximum observed plasma concentration of niraparib and abiraterone acetate (AA) after a single dose.

  Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1

• Combination 3: Maximum Observed Plasma Concentration (Cmax) of Niraparib Normalized by the Dose(Niraparib) (Cmax/Dose) of Niraparib Administered With AA After a Single Dose

  Cmax/dose of niraparib was defined as maximum observed plasma concentration of niraparib Cmax normalized by the dose of niraparib administered with AA after a single dose.

  Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1

• Combination 3: Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC [0-168hr]) of Niraparib Administered With AA After a Single Dose

  AUC(0-168 hours) was defined as area under the plasma concentration-time curve from time zero to 168 hours of Niraparib administered with AA After a single dose.

  Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1

• Combination 3: Area Under the Plasma Concentration-Time Curve for Niraparib From Time Zero to 168 Hours (AUC [0-168 Hours]/Dose) of Niraparib Administered With AA After a Single Dose

  AUC0(168 hours)/dose was defined as area under the plasma concentration-time curve for niraparib from time 0 to 168 hours of niraparib administered with AA after a single dose.

  Pre-dose, 30 min, 1 hour (hr), 1.5 hr, 2hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 24 hr, 48 hr, 72 hr, and 168 hr post dose on Day 1

Secondary Outcomes (16)

• Combination 1: Parts 1 and 2: Plasma Concentrations of Niraparib

  Day 1

• Combination 1: Parts 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Niraparib

  Day 1

• Combination 1: Parts 1 and 2: Time to Reach the Maximum Plasma Concentration (Tmax) of Niraparib

  Day 1

• Combination 1: Parts 1 and 2: Minimum Observed (Predose) Concentration Following Multiple Dosing (Ctrough) of Niraparib

  Day 1

• Combination 1: Parts 1 and 2: Number of Participants With Anti-drug Antibodies of Niraparib

  From baseline up to end of study (6 years 10 months)

Study Arms (4)

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

EXPERIMENTAL

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.

Drug: Niraparib 200 mg; Drug: Cetrelimab 240 mg; Drug: Cetrelimab 480 mg

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

EXPERIMENTAL

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.

Drug: Niraparib 200 mg; Drug: Cetrelimab 480 mg

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

EXPERIMENTAL

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.

Drug: Niraparib 200 mg; Drug: Abiraterone acetate 1000 mg; Drug: Prednisone 5 mg

Combination 3: Niraparib + AA-P

EXPERIMENTAL

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.

Drug: Niraparib 200 mg; Drug: Abiraterone acetate 1000 mg; Drug: Prednisone 5 mg

Interventions

Niraparib 200 mg DRUG

Participants will receive niraparib 200 mg orally.

Combination 1:Dose Expansion: Niraparib + cetrelimab (Part 2); Combination 1:Dose Selection: Niraparib + cetrelimab (Part 1); Combination 2: Dose Expansion: Niraparib + AA-P (Part 2); Combination 3: Niraparib + AA-P

Cetrelimab 240 mg DRUG

Participants will receive cetrelimab 240 mg IV every 2 weeks.

Also known as: JNJ-63723283

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

Cetrelimab 480 mg DRUG

Participants will receive cetrelimab 480 mg IV every 4 weeks.

Also known as: JNJ-63723283

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

Abiraterone acetate 1000 mg DRUG

Participants will receive AA 1000 mg orally.

Combination 2: Dose Expansion: Niraparib + AA-P (Part 2); Combination 3: Niraparib + AA-P

Prednisone 5 mg DRUG

Participants will receive prednisone 5 mg orally.

Combination 2: Dose Expansion: Niraparib + AA-P (Part 2); Combination 3: Niraparib + AA-P

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (50)

Urological Associates of Southern Arizona, P.C.

Tucson, Arizona, 85741, United States

Location

The Urology Center of Colorado

Denver, Colorado, 80211, United States

Location

Mayo Clinic - Division Of Hematology/oncology

Jacksonville, Florida, 32224, United States

Location

First Urology, PSC

Jeffersonville, Indiana, 47130, United States

Location

Chesapeake Urology Research Associates

Towson, Maryland, 21204, United States

Location

Michigan Institute of Urology

Troy, Michigan, 48084, United States

Location

New York Oncology Hematology

Albany, New York, 12208, United States

Location

Memorial Sloan Kettering Cancer Center 1

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center (UPMC)

Pittsburgh, Pennsylvania, 15232, United States

Location

MUSC-Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Urology Associates

Nashville, Tennessee, 37209, United States

Location

Houston Metro Urology

Houston, Texas, 77027, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Utah Cancer Specialists

Salt Lake City, Utah, 84106, United States

Location

Urology of Virginia, PLCC

Virginia Beach, Virginia, 23462, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 5379200, United States

Location

OLV Ziekenhuis Aalst

Aalst, 9300, Belgium

Location

ZNA Middelheim

Antwerp, 2020, Belgium

Location

ULB Hôpital Erasme

Brussels, 1070, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Az Groeninge

Kortrijk, 8500, Belgium

Location

Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman

Liège, B-4000, Belgium

Location

Southern Alberta Institute of Urology / Prostate Cancer Centre

Calgary, Alberta, T2V 1P9, Canada

Location

British Columbia Cancer Agency

Vancouver, British Columbia, V5Z4E6, Canada

Location

Princess Margaret Cancer Centre University Health Network

Toronto, Ontario, M5G2M9, Canada

Location

Centre de Recherche du CHUM

Montreal, Quebec, H2X 0A9, Canada

Location

Asaf Harofe Medical Center

Beer Yaakov, 60930, Israel

Location

Soroka Hospital

Beersheba, 85101, Israel

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Sheba Medical Center Tel Hashomer

Ramat Gan, 52621, Israel

Location

Azienda Ospedaliera Universitaria Careggi di Firenze

Florence, 50134, Italy

Location

Azienda Ospedaliera ''Vito Fazzi''

Lecce, 73100, Italy

Location

UOC Oncologia Ospedale Provinciale di Macerata

Macerata, 62100, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

IRCCS-Fondazione Pascale

Naples, 80131, Italy

Location

Hosp. de La Santa Creu I Sant Pau

Barcelona, 08025, Spain

Location

Hospital Vall D'Hebron

Barcelona, 8035, Spain

Location

Hosp. Univ. de La Princesa

Madrid, 28006, Spain

Location

Hosp Univ Fund Jimenez Diaz

Madrid, 28040, Spain

Location

Hosp Univ Hm Sanchinarro

Madrid, 28050, Spain

Location

Hosp Virgen de La Victoria

Málaga, 29010, Spain

Location

Royal United Hospital

Bath, BA1 3NG, United Kingdom

Location

University College London Hospitals

London, WC1E 6BT, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

The Royal Marsden NHS Trust Sutton

Sutton, SM2 5PT, United Kingdom

Location

Royal Cornwall Hospitals NHS Trust - Royal Cornwall Hospital

Truro, TR1 3LJ, United Kingdom

Location

MeSH Terms

Conditions

Prostatic Neoplasms, Castration-Resistant

Interventions

niraparib; Abiraterone Acetate; Prednisone

Condition Hierarchy (Ancestors)

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Results Point of Contact

• Title: Executive Medical Director Oncology
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2018
• First Posted: February 13, 2018
• Study Start: March 2, 2018
• Primary Completion: August 31, 2021
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 13, 2026
• Results First Posted: November 18, 2023

Record last verified: 2026-04

Locations

IT (5); US (19); IL (5); GB (5); CA (4); BE (6); ES (6)