A Phase 1b-2 Study of Niraparib Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer

Condition: Prostatic Neoplasms, Castration-Resistant

Intervention:

Drug: Niraparib 200 mg
Drug: JNJ-63723283 240 mg
Drug: JNJ-63723283 480 mg
Drug: Abiraterone Acetate
Drug: Prednisone

Purpose: The purpose of this study is to establish the recommended phase 2 dose (RP2D) of niraparib combination therapies of Part 1 and to evaluate the antitumor activity and safety of niraparib combination therapies of Part 2.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03431350

Sponsor: Janssen Research & Development, LLC

Primary Outcome Measures:

Measure: Part 1: Combination 1: Incidence of Specified Toxicities
Time Frame: Up to 28 days
Safety Issue:
Measure: Part 2: Combination 1: Objective Response Rate (ORR)
Time Frame: Approximately 24 months
Safety Issue:
Measure: Part 2: Combination 2: Composite Response Rate (RR)
Time Frame: Approximately 24 months
Safety Issue:
Measure: Part 2: Combinations 1 and 2: Incidence of Adverse Events (AEs)
Time Frame: Approximately 24 months
Safety Issue:
Measure: Part 2: Combinations 1 and 2: Severity of Adverse Events
Time Frame: Approximately 24 months
Safety Issue:

Secondary Outcome Measures:

Measure: Part 1 and Part 2 (Combination 1): Plasma Concentrations of Niraparib and JNJ-63723283
Time Frame: Cycle 1 up to 12 (each cycle is of 28 days)
Safety Issue:
Measure: Part 1 and Part 2 (Combination 1): Number of participants with Anti-Drug Antibodies
Time Frame: Approximately 24 months
Safety Issue:
Measure: Part 2: Combinations 1 and 2: Number of Participants with Circulating Tumor Cell (CTC) Response
Time Frame: From screening up to end of treatment (30 days of last dose) (approximately up to 24 months)
Safety Issue:
Measure: Part 2: Combination 1: Composite Response Rate (RR)
Time Frame: Screening, Cycle 1 (each cycle of 28 days) Day 1 (every 8 weeks for the first 6 months and then every 12 weeks thereafter) until follow-up phase (for 3 months) (approximately up to 24 months)
Safety Issue:
Measure: Part 2: Combination 2: Objective Response Rate (ORR)
Time Frame: Approximately 24 months
Safety Issue:
Measure: Part 2: Combinations 1 and 2: Duration of Objective Response
Time Frame: Screening, Cycle 1 (each cycle of 28 days) Day 1 (every 8 weeks for the first 6 months and then every 12 weeks thereafter) until follow-up phase (approximately up to 24 months)
Safety Issue:
Measure: Part 2: Combinations 1 and 2: Overall Survival (OS)
Time Frame: Up to follow-up (approximately up to 24 months)
Safety Issue:

Estimated Enrollment: 150

Study Start Date: March 2, 2018

Phase: Phase 1/Phase 2

Eligibility:

Age: minimum 18 Years maximum N/A
Gender: Male

Inclusion Criteria:

Participants willing to undergo all protocol-specified biopsies
Diagnosis of prostate adenocarcinoma as confirmed by the investigator Combination 1:
Must have determination of biomarker (BM) status for DNA-repair gene defects (DRD) (either BM positive [+] or BM negative [-]) by the sponsor’s blood or tissue assay
Participants must have measurable disease as defined by response evaluation criteria in solid tumors (RECIST) 1.1 (soft tissue lesion of greater than or equal to (>=) 10 millimeter (mm) in the long axis or extrapelvic lymph node of >=15 mm in the short axis)
Must have previously received at least 1, but no more than 2, lines of novel androgen receptor (AR)-targeted therapy (that is, abiraterone acetate with prednisone, enzalutamide) for metastatic castration-resistant prostate cancer (mCRPC). Participants must have had at least 4 weeks of AR-targeted therapy Combination 2:
Must be biomarker positive for DRD by either the sponsor’s blood or tissue assay
Must have progressed on 1 prior line of novel AR-targeted therapy (that is, abiraterone acetate with prednisone, enzalutamide) for mCRPC. Prior treatment with taxane-based therapy and AR-targeted therapy outside of the mCRPC setting is allowed

Exclusion Criteria:

Prior treatment with a poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor
History or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
Active malignancy (exceptions: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently remission) less than or equal to (<=) 2 years prior to enrollment
Active infection requiring systemic therapy
Allergies, hypersensitivity, or intolerance to niraparib or the corresponding excipients

Contact:

Study Contact
844-434-4210

Locations:

Urological Associates of Southern Arizona, P.C.
Tucson Arizona 85741 United States

The Urology Center of Colorado
Denver Colorado 80211 United States

University of Florida
Jacksonville Florida 32209 United States

Mayo Clinic – Division Of Hematology/oncology
Jacksonville Florida 32224 United States

Florida Hospital
Orlando Florida 32804 United States

Chesapeake Urology Research Associates
Towson Maryland 21204 United States

Massachusetts General
Boston Massachusetts 02114 United States

Michigan Institute of Urology
Troy Michigan 48084 United States

Memorial Sloan Kettering Cancer Center
Harrison New York 10604 United States

Memorial Sloan Kettering Cancer Center
New York New York 10065 United States

Thomas Jefferson University
Philadelphia Pennsylvania 19107 United States

MUSC-Hollings Cancer Center
Charleston South Carolina 29425 United States

Carolina Urologic Research Center
Myrtle Beach South Carolina 29572 United States

The University of Texas MD Anderson Cancer Center
Houston Texas 77030 United States

Intermountain Healthcare
Saint George Utah 84770 United States

University of Utah Huntsman Cancer Institute
Salt Lake City Utah 84112 United States

Utah Cancer Specialists
Salt Lake City Utah 84121 United States

Urology of Virginia, PLCC
Virginia Beach Virginia 23462 United States

University of Wisconsin Carbone Cancer Center
Madison Wisconsin 5379200 United States

OLV Ziekenhuis Aalst
Aalst 9300 Belgium

ZNA Middelheim
Antwerpen 2020 Belgium

ULB Hôpital Erasme
Brussels 1070 Belgium

Universitair Ziekenhuis Gent
Gent 9000 Belgium

Az Groeninge
Kortrijk 8500 Belgium

Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman
Liege B-4000 Belgium

Southern Alberta Institute of Urology / Prostate Cancer Centre
Calgary Alberta T2V 1P9 Canada

University Health Network (UHN) Princess Margaret Cancer Centre
Toronto Ontario M5G 2M9 Canada

Centre de Recherche du CHUM
Montreal Quebec H2X 0A9 Canada

British Columbia Cancer Agency
Vancouver V5Z4E6 Canada

Asaf Harofe Medical Center
Beer Yaakov 60930 Israel

Rambam Medical Center
Haifa 31096 Israel

Rabin Medical Center
Petach Tikva 49100 Israel

Sheba Medical Center Tel Hashomer
Ramat Gan 52621 Israel

Azienda USL Toscana Sud Est -Ospedale di Grosseto
Arezzo 52100 Italy

Policlinico Sant’Orsola Malpighi
Bologna 40138 Italy

Azienda Ospedaliera Spedali Civili di Brescia
Brescia 25123 Italy

Oncologia Azienda Ospedaliera “Istituti Ospitalieri” di Cremona
Cremona 26100 Italy

Azienda Ospedaliera Universitaria Careggi di Firenze
Firenze 50134 Italy

Azienda Ospedaliera “Vito Fazzi”
Lecce 73100 Italy

UOC Oncologia Ospedale Provinciale di Macerata
Macerata 62100 Italy

ASST Grande Ospedale Metropolitano Niguarda
Milano 20162 Italy

IRCCS-Fondazione Pascale
Napoli 80131 Italy

Policlinico Universitario Agostino Gemelli
Roma 00168 Italy

Hosp. de La Santa Creu I Sant Pau
Barcelona 08025 Spain

Hospital Vall D’Hebron
Barcelona 08035 Spain

Hosp. Univ. de La Princesa
Madrid 28006 Spain

Hosp. Gral. Univ. Gregorio Maranon
Madrid 28007 Spain

Hosp. Univ. Fund. Jimenez Diaz
Madrid 28040 Spain

Hosp. Univ. Hm Sanchinarro
Madrid 28050 Spain

Hosp. Virgen de La Victoria
Malaga 29010 Spain

Royal United Hospital
Bath BA1 3NG United Kingdom

Guy’s Hospital
London SE1 9RT United Kingdom

University College London Hospitals
London WC1E 6BT United Kingdom

Southampton General Hospital
Southampton SO16 6YD United Kingdom

The Royal Marsden NHS Trust Sutton
Sutton SM2 5PT United Kingdom

Royal Cornwall Hospitals NHS Trust – Royal Cornwall Hospital
Truro TR1 3LJ United Kingdom

View trial on ClinicalTrials.gov