A Safety and Pharmacokinetics Study of Niraparib Plus an Androgen Receptor-Targeted Therapy in Men With Metastatic Castration-Resistant Prostate Cancer (BEDIVERE)

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT02924766

Collaborator

(none)

Enrollment

Locations

Arm

33.5

Actual Duration (Months)

5.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and pharmacokinetics of niraparib when administered in combination with an androgen receptor (AR)-targeted therapy (apalutamide or abiraterone acetate plus prednisone) in adult men with metastatic castration resistant prostate cancer (mCRPC) who may or may not have deoxyribonucleic acid (DNA)-repair anomalies.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms	Drug: Niraparib Drug: Apalutamide Drug: Abiraterone Acetate Drug: Prednisone	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Safety and Pharmacokinetics Study of Niraparib Plus Androgen Receptor-Targeted Therapy (Apalutamide or Abiraterone Acetate Plus Prednisone) in Men With Metastatic Castration-Resistant Prostate Cancer

Actual Study Start Date :

Oct 3, 2016

Actual Primary Completion Date :

Jul 18, 2019

Actual Study Completion Date :

Jul 19, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Niraparib + Apalutamide/[Abiraterone Acetate + Prednisone] Participants will receive initial starting dose of Niraparib 200 milligram (mg) once daily in combination either with Apalutamide 240 mg (460 mg) once daily or Abiraterone Acetate 1000 mg (4250 mg) plus 10 mg Prednisone (5 mg twice daily) for 28 days of cycle 1. Once a safe dose of niraparib is selected with each Andrgen Receptor (AR)-targeted therapy [Apalutamide or Abiraterone Acetate plus Prednisone], then an expansion phase (Part 2) will open to further explore safety and assess antitumor activity.	Drug: Niraparib Participants will start with niraparib 200 mg once daily. Other Names: JNJ-64091742 Drug: Apalutamide Participants will receive apalutamide 240 mg (460 mg) once daily orally. Other Names: ARN-509 Drug: Abiraterone Acetate* Participants will receive 1000 mg (4250mg) once daily. Other Names: ZYTIGA Drug: Prednisone* Participants will receive 10 mg (1*5 mg twice daily).

Arm

Intervention/Treatment

Experimental: Niraparib + Apalutamide/[Abiraterone Acetate + Prednisone]

Participants will receive initial starting dose of Niraparib 200 milligram (mg) once daily in combination either with Apalutamide 240 mg (4*60 mg) once daily or Abiraterone Acetate 1000 mg (4*250 mg) plus 10 mg Prednisone (5 mg twice daily) for 28 days of cycle 1. Once a safe dose of niraparib is selected with each Andrgen Receptor (AR)-targeted therapy [Apalutamide or Abiraterone Acetate plus Prednisone], then an expansion phase (Part 2) will open to further explore safety and assess antitumor activity.

Drug: Niraparib

Participants will start with niraparib 200 mg once daily.

Other Names:

JNJ-64091742

Drug: Apalutamide

Participants will receive apalutamide 240 mg (4*60 mg) once daily orally.

Other Names:

ARN-509

Drug: Abiraterone Acetate

Participants will receive 1000 mg (4*250mg) once daily.

Other Names:

ZYTIGA

Drug: Prednisone

Participants will receive 10 mg (1*5 mg twice daily).

Outcome Measures

Primary Outcome Measures

Determine Recommended Phase 2 dose (RP2D) of Niraparib in Combination With 240 milligram (mg) Apalutamide or 1,000 mg Abiraterone Acetate Plus 10 mg Prednisone (5 mg Twice Daily) in Part 1 [Up to 56 days]
RP2D will be defined as the highest dose of study drug at which less than 33 percent (%) of participants experience dose limiting toxicity (DLT).
Number of Participants With Incidence and Severity of Adverse Events (Part 2) [Up to 30 days after last dose]
Number of participants will be assessed to further explore safety and antitumor activity in Part 2 (dose expansion) of study.

Secondary Outcome Measures

Maximum Observed Plasma Concentration (Cmax) [24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days)]
Maximum observed plasma concentration (Cmax) will be assessed.
Time to Reach the Maximum Observed Plasma Concentration (Tmax) [24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days)]
Time to reach the maximum plasma concentration(Tmax) will be assessed.
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC [0-24]) [24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days)]
Area under plasma concentration-time curve from time 0 to time 24 hours after dosing will be assessed.
Trough Plasma Concentration (Ctrough) [Predose (Cycle 1 Days 15 and 22) up to Cycle 3 Day 1 (each cycle 28 days) then Every 3 Cycles after Cycle 3 till End of Treatment (30 days after last dose)]
Ctrough is the minimum observed (that is, predose) plasma concentration following multiple dosing will be assessed.
Metabolite to Parent Ratio for Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC [0-24]) [24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days)]
Metabolite to parent drug ratio for area under the plasma concentration-time curve from time 0 to 24 hours (AUC [0-24]) will be assessed.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed prostate cancer (mixed histology is acceptable, with the exception of the small cell pure phenotype, which is be excluded
At least 1 line of prior taxane-based chemotherapy
At least 1 line of prior androgen receptor (AR) targeted therapy
Progression of metastatic prostate cancer in the setting of castrate levels of testosterone or history of bilateral orchiectomy at study entry
Eastern Cooperative Oncology Group Performance Status (ECOG PS) of lesser than or equal to [<=]1

Exclusion Criteria:

Known brain metastases or history of seizure
Prior treatment with a poly (adenosine diphosphate [ADP] ribose) polymerase (PARP) inhibitor
Prior platinum-based chemotherapy for the treatment of prostate cancer
Known history or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
Severe or unstable cardiovascular disease or uncontrolled hypertension
Left ventricular ejection fraction (LVEF) of lesser than [<] 50 percent (%) as determined by multiple uptake gated acquisition (MUGA) or echocardiography during screening

Contacts and Locations

Locations

	City	State	Country
1	West Hollywood	California	United States
2	Louisville	Kentucky	United States
3	Portland	Oregon	United States
4	Myrtle Beach	South Carolina	United States
5	Vancouver	British Columbia	Canada
6	Montreal	Quebec	Canada