Prostatic Neoplasms
Conditions
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.
Interventions
DRUGNiraparib
Participants will start with niraparib 200 mg once daily.
DRUGApalutamide
Participants will receive apalutamide 240 mg (4\*60 mg) once daily orally.
DRUGAbiraterone Acetate
Participants will receive 1000 mg (4\*250mg) once daily.
DRUGPrednisone
Participants will receive 10 mg (1\*5 mg twice daily).
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Canada, United States
Outcome results
None listed