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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Prostatic Neoplasms

Intervention / Treatment
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* Drug: Niraparib
* Drug: Apalutamide
* Drug: Abiraterone Acetate
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Niraparib + Apalutamide/[Abiraterone Acetate + Prednisone]<br>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<br>* Participants will start with niraparib 200 mg once daily.<br>* Other names: JNJ-64091742;Drug: Apalutamide<br>* Participants will receive apalutamide 240 mg (4*60 mg) once daily orally.<br>* Other names: ARN-509;Drug: Abiraterone Acetate<br>* Participants will receive 1000 mg (4*250mg) once daily.<br>* Other names: ZYTIGA;Drug: Prednisone<br>* Participants will receive 10 mg (1*5 mg twice daily).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | RP2D will be defined as the highest dose of study drug at which less than 33 percent (%) of participants experience dose limiting toxicity (DLT). | Up to 56 days | 
| Number of Participants With Incidence and Severity of Adverse Events (Part 2) | Number of participants will be assessed to further explore safety and antitumor activity in Part 2 (dose expansion) of study. | Up to 30 days after last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) | Maximum observed plasma concentration (Cmax) will be assessed. | 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 Observed Plasma Concentration (Tmax) | Time to reach the maximum plasma concentration(Tmax) will be assessed. | 24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days) | 
| Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC [0-24]) | Area under plasma concentration-time curve from time 0 to time 24 hours after dosing will be assessed. | 24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days) | 
| Trough Plasma Concentration (Ctrough) | Ctrough is the minimum observed (that is, predose) plasma concentration following multiple dosing will be assessed. | 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) | 
| Metabolite to Parent Ratio for Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC [0-24]) | 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. | 24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days) |