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

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

Sponsors

Lead Sponsor: Janssen Research & Development, LLC

Source Janssen Research & Development, LLC
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).

Detailed Description

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.

Overall Status Recruiting
Start Date 2018-03-02
Completion Date 2021-12-31
Primary Completion Date 2021-10-15
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Part 1: Combination 1: Incidence of Specified Toxicities Up to Day 28
Part 2: Combination 1: Objective Response Rate (ORR) Up to 42 months
Part 2: Combinations 1: Incidence of Adverse Events (AEs) Up to 42 months
Part 2: Combinations 1: Severity of Adverse Events Up to 42 months
Part 2: Combination 2: Composite Response Rate (RR) Up to 42 months
Combination 3: Maximum Observed Analyte Plasma Concentration (Cmax) of Niraparib and AA After a Single Dose Up to 168 hours postdose
Combination 3: Maximum Observed Analyte Plasma Concentration for Niraparib Normalized by the Dose (Cmax/dose) of Niraparib and AA After a Single Dose Up to 168 hours postdose
Combination 3: Area Under the Plasma Concentration-Time Curve from Time Zero to 168 Hours (AUC [0-168]) of Niraparib and AA After a Single Dose Up to 168 hours postdose
Combination 3: Area Under the Plasma Concentration-Time Curve for Niraparib from Time Zero to 168 Hours (AUC [0-168]/dose) of Niraparib and AA After a Single Dose Up to 168 hours postdose
Secondary Outcome
Measure Time Frame
Part 2: Combination 1: Number of Participants with Circulating Tumor Cell (CTC) Response Up to 42 months
Part 2: Combination 1: Composite Response Rate (RR) Up to 42 months
Part 2: Combination 1: Duration of Objective Response Up to 42 months
Part 2: Combination 1: Overall Survival (OS) Up to 46 months
Part 2: Combination 2: Objective Response Rate (ORR) Up to 42 months
Combination 3: Number of Participants with Adverse Events Up to 46 months
Combination 3: Number of Participants with Abnormal Clinical Laboratory Findings Up to 46 months
Enrollment 140
Condition
Intervention

Intervention Type: Drug

Intervention Name: Niraparib 200 mg

Description: Participants will receive niraparib 200 mg orally.

Intervention Type: Drug

Intervention Name: Cetrelimab 240 mg

Description: Participants will receive cetrelimab 240 mg IV every 2 weeks.

Arm Group Label: Combination 1:Dose Selection: Niraparib + cetrelimab (Part 1)

Other Name: JNJ-63723283

Intervention Type: Drug

Intervention Name: Cetrelimab 480 mg

Description: Participants will receive cetrelimab 480 mg IV every 4 weeks.

Other Name: JNJ-63723283

Intervention Type: Drug

Intervention Name: Abiraterone acetate 1000 mg

Description: Participants will receive AA 1000 mg orally.

Intervention Type: Drug

Intervention Name: Prednisone 5 mg

Description: Participants will receive prednisone 5 mg orally.

Eligibility

Criteria:

Inclusion Criteria for Combination 3: - 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

Gender:

Male

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Janssen Research & Development, LLC Clinical Trial Study Director Janssen Research & Development, LLC
Overall Contact

Last Name: Study Contact

Phone: 844-434-4210

Email: [email protected]

Location
Facility: Status:
Urology Centers Of Alabama | Homewood, Alabama, 35209, United States Withdrawn
Mayo Clinic Arizona | Phoenix, Arizona, 85054, United States Withdrawn
Urological Associates of Southern Arizona, P.C. | Tucson, Arizona, 85741, United States Completed
The Urology Center of Colorado | Denver, Colorado, 80211, United States Recruiting
University of Florida | Jacksonville, Florida, 32209, United States Withdrawn
Mayo Clinic - Division Of Hematology/oncology | Jacksonville, Florida, 32224, United States Completed
Florida Hospital | Orlando, Florida, 32804, United States Withdrawn
First Urology, PSC | Jeffersonville, Indiana, 47130, United States Completed
Chesapeake Urology Research Associates | Towson, Maryland, 21204, United States Recruiting
Massachusetts General | Boston, Massachusetts, 02114, United States Withdrawn
Michigan Institute of Urology | Troy, Michigan, 48084, United States Recruiting
New York Oncology Hematology | Albany, New York, 12208, United States Completed
Memorial Sloan Kettering Cancer Center | Harrison, New York, 10604, United States Completed
Memorial Sloan Kettering Cancer Center | New York, New York, 10065, United States Completed
Clinical Research Solutions, LLC | Middleburg Heights, Ohio, 44130, United States Withdrawn
Oregon Urology Institute | Springfield, Oregon, 97477, United States Withdrawn
Urologic Consultants of SE PA | Bala-Cynwyd, Pennsylvania, 19004, United States Withdrawn
Thomas Jefferson University | Philadelphia, Pennsylvania, 19107, United States Recruiting
University of Pittsburgh Medical Center (UPMC) | Pittsburgh, Pennsylvania, 15232, United States Recruiting
MUSC-Hollings Cancer Center | Charleston, South Carolina, 29425, United States Completed
Carolina Urologic Research Center | Myrtle Beach, South Carolina, 29572, United States Recruiting
Urology Associates | Nashville, Tennessee, 37209, United States Completed
Houston Metro Urology | Houston, Texas, 77027, United States Completed
The University of Texas MD Anderson Cancer Center | Houston, Texas, 77030, United States Recruiting
Intermountain Healthcare | Saint George, Utah, 84770, United States Withdrawn
Utah Cancer Specialists | Salt Lake City, Utah, 84106, United States Recruiting
University of Utah Huntsman Cancer Institute | Salt Lake City, Utah, 84112, United States Withdrawn
Urology of Virginia, PLCC | Virginia Beach, Virginia, 23462, United States Recruiting
University of Wisconsin Carbone Cancer Center | Madison, Wisconsin, 5379200, United States Recruiting
OLV Ziekenhuis Aalst | Aalst, 9300, Belgium Active, not recruiting
ZNA Middelheim | Antwerpen, 2020, Belgium Active, not recruiting
ULB Hôpital Erasme | Brussels, 1070, Belgium Completed
Universitair Ziekenhuis Gent | Gent, 9000, Belgium Completed
Az Groeninge | Kortrijk, 8500, Belgium Active, not recruiting
Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman | Liege, B-4000, Belgium Active, not recruiting
Southern Alberta Institute of Urology / Prostate Cancer Centre | Calgary, Alberta, T2V 1P9, Canada Completed
British Columbia Cancer Agency | Vancouver, British Columbia, V5Z4E6, Canada Active, not recruiting
University Health Network (UHN) Princess Margaret Cancer Centre | Toronto, Ontario, M5G 2M9, Canada Completed
Centre de Recherche du CHUM | Montreal, Quebec, H2X 0A9, Canada Recruiting
Asaf Harofe Medical Center | Beer Yaakov, 60930, Israel Active, not recruiting
Soroka Hospital | Beer-Sheva, 85101, Israel Completed
Rambam Medical Center | Haifa, 31096, Israel Completed
Rabin Medical Center | Petach Tikva, 49100, Israel Active, not recruiting
Sheba Medical Center Tel Hashomer | Ramat Gan, 52621, Israel Completed
Azienda USL Toscana Sud Est -Ospedale di Grosseto | Arezzo, 52100, Italy Withdrawn
Policlinico Sant'Orsola Malpighi | Bologna, 40138, Italy Withdrawn
Azienda Ospedaliera Spedali Civili di Brescia | Brescia, 25123, Italy Withdrawn
Oncologia Azienda Ospedaliera ''Istituti Ospitalieri'' di Cremona | Cremona, 26100, Italy Withdrawn
Azienda Ospedaliera Universitaria Careggi di Firenze | Firenze, 50134, Italy Active, not recruiting
Azienda Ospedaliera ''Vito Fazzi'' | Lecce, 73100, Italy Active, not recruiting
UOC Oncologia Ospedale Provinciale di Macerata | Macerata, 62100, Italy Completed
ASST Grande Ospedale Metropolitano Niguarda | Milano, 20162, Italy Active, not recruiting
IRCCS-Fondazione Pascale | Napoli, 80131, Italy Completed
Policlinico Universitario Agostino Gemelli | Roma, 00168, Italy Withdrawn
Hosp. de La Santa Creu I Sant Pau | Barcelona, 08025, Spain Completed
Hospital Vall D'Hebron | Barcelona, 8035, Spain Completed
Hosp. Univ. de La Princesa | Madrid, 28006, Spain Completed
Hosp. Gral. Univ. Gregorio Marañon | Madrid, 28007, Spain Withdrawn
Hosp. Univ. Fund. Jimenez Diaz | Madrid, 28040, Spain Completed
Hosp. Univ. Hm Sanchinarro | Madrid, 28050, Spain Active, not recruiting
Hosp. Virgen de La Victoria | Malaga, 29010, Spain Completed
Royal United Hospital | Bath, BA1 3NG, United Kingdom Completed
Guy's Hospital | London, SE1 9RT, United Kingdom Withdrawn
University College London Hospitals | London, WC1E 6BT, United Kingdom Completed
Southampton General Hospital | Southampton, SO16 6YD, United Kingdom Recruiting
The Royal Marsden NHS Trust Sutton | Sutton, SM2 5PT, United Kingdom Active, not recruiting
Royal Cornwall Hospitals NHS Trust - Royal Cornwall Hospital | Truro, TR1 3LJ, United Kingdom Completed
Location Countries

Belgium

Canada

Israel

Italy

Spain

United Kingdom

United States

Verification Date

2021-08-01

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

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

Type: Experimental

Description: 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.

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

Type: Experimental

Description: 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.

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

Type: Experimental

Description: 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.

Label: Combination 3: Niraparib + AA-P

Type: Experimental

Description: 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.

Acronym QUEST
Study Design Info

Allocation: Non-Randomized

Intervention Model: Sequential Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Research News