Clinical trial NCT03431350: A Study of Niraparib Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer
Official title: A Phase 1b-2 Study of Niraparib Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Prostatic Neoplasms, Castration-Resistant
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2018-02-13
Enrollment: 136
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Combination 1: Part 1: Number of Participants With Specified Toxicity
timeFrame: Cycle 1 (28 days)
measure: Combination 1: Part 2: Objective Response Rate (ORR)
timeFrame: Up to 37 months
measure: Combination 2: Composite Response Rate (RR)
timeFrame: Up to 31 months
measure: Combination 1: Part 2: Number of Participants With Adverse Events (AEs)
timeFrame: Up to 37 months
measure: Combination 2: Number of Participants With Adverse Events (AEs)
timeFrame: Up to 31 months
measure: Combination 1: Part 2: Number of Participants With Adverse Events (AEs) of Grade >=3 Severity
timeFrame: Up to 37 months
measure: Combination 2: Number of Participants With Adverse Events (AEs) of Grade >=3 Severity
timeFrame: Up to 31 months
measure: Combination 3: Maximum Observed Plasma Concentration (Cmax) of Niraparib and Abiraterone Acetate After a Single Dose
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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:
measure: Combination 1: Parts 1 and 2: Plasma Concentrations of Niraparib
timeFrame: Day 1
measure: Combination 1: Parts 1 and 2: Maximum Observed Plasma Concentration (Cmax) of Niraparib
timeFrame: Day 1
measure: Combination 1: Parts 1 and 2: Time to Reach the Maximum Plasma Concentration (Tmax) of Niraparib
timeFrame: Day 1
measure: Combination 1: Parts 1 and 2: Minimum Observed (Predose) Concentration Following Multiple Dosing (Ctrough) of Niraparib
timeFrame: Day 1
measure: Combination 1: Parts 1 and 2: Number of Participants With Anti-drug Antibodies of Niraparib
timeFrame: From baseline up to end of study (6 years 10 months)
measure: Combination 1: Part 2 and Combination 2: Circulating Tumor Cells (CTC) Response
timeFrame: From baseline up to end of study (6 years 10 months)
measure: Combination 1: Part 2: Composite Response Rate
timeFrame: From baseline up to end of study (6 years 10 months)
measure: Combination 2: Objective Response Rate (ORR)
timeFrame: From baseline up to end of study (6 years 10 months)
measure: Combination 1: Part 2 and Combination 2: Duration of Objective Response
timeFrame: From baseline up to end of study (6 years 10 months)
measure: Combination 1: Part 2 and Combination 2: Overall Survival
timeFrame: From baseline up to end of study (6 years 10 months)
measure: Combination 3: Cmax of Niraparib and Abiraterone Acetate After a Single Dose For Low-strength FDC
timeFrame: 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
measure: 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 for Low-strength FDC
timeFrame: 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
measure: 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 For Low-strength FDC
timeFrame: 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
measure: 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 For Low-strength FDC
timeFrame: 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
measure: Combination 3: Number of Participants With Adverse Events
timeFrame: From baseline up to end of study (6 years 10 months)
measure: Combination 3: Number of Participants With Clinical Laboratory Parameters
timeFrame: From baseline up to end of study (6 years 10 months)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Urological Associates of Southern Arizona, P.C.
state: Arizona
city: Denver
country: United States
facility: The Urology Center of Colorado
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic - Division Of Hematology/oncology
state: Florida
city: Jeffersonville
country: United States
facility: First Urology, PSC
state: Indiana
city: Towson
country: United States
facility: Chesapeake Urology Research Associates
state: Maryland
city: Troy
country: United States
facility: Michigan Institute of Urology
state: Michigan
city: Albany
country: United States
facility: New York Oncology Hematology
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC)
state: Pennsylvania
city: Charleston
country: United States
facility: MUSC-Hollings Cancer Center
state: South Carolina
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Nashville
country: United States
facility: Urology Associates
state: Tennessee
city: Houston
country: United States
facility: Houston Metro Urology
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Virginia Beach
country: United States
facility: Urology of Virginia, PLCC
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
city: Aalst
country: Belgium
facility: OLV Ziekenhuis Aalst
city: Antwerpen
country: Belgium
facility: ZNA Middelheim
city: Brussels
country: Belgium
facility: ULB Hôpital Erasme
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Kortrijk
country: Belgium
facility: Az Groeninge
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman
city: Calgary
country: Canada
facility: Southern Alberta Institute of Urology / Prostate Cancer Centre
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre University Health Network
state: Ontario
city: Montreal
country: Canada
facility: Centre de Recherche du CHUM
state: Quebec
city: Beer Yaakov
country: Israel
facility: Asaf Harofe Medical Center
city: Beer-Sheva
country: Israel
facility: Soroka Hospital
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center Tel Hashomer
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi di Firenze
city: Lecce
country: Italy
facility: Azienda Ospedaliera ''Vito Fazzi''
city: Macerata
country: Italy
facility: UOC Oncologia Ospedale Provinciale di Macerata
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Napoli
country: Italy
facility: IRCCS-Fondazione Pascale
city: Barcelona
country: Spain
facility: Hosp. de La Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Hospital Vall D'Hebron
city: Madrid
country: Spain
facility: Hosp. Univ. de La Princesa
city: Madrid
country: Spain
facility: Hosp Univ Fund Jimenez Diaz
city: Madrid
country: Spain
facility: Hosp Univ Hm Sanchinarro
city: Malaga
country: Spain
facility: Hosp Virgen de La Victoria
city: Bath
country: United Kingdom
facility: Royal United Hospital
city: London
country: United Kingdom
facility: University College London Hospitals
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Trust Sutton
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospitals NHS Trust - Royal Cornwall Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: