Clinical trial NCT02924766: A Safety and Pharmacokinetics Study of Niraparib Plus an Androgen Receptor-Targeted Therapy in Men With Metastatic Castration-Resistant Prostate Cancer (BEDIVERE)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostatic Neoplasms
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2016-10-05
Enrollment: 34
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Up to 56 days
measure: Number of Participants With Incidence and Severity of Adverse Events (Part 2)
timeFrame: Up to 30 days after last dose
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days)
measure: Time to Reach the Maximum Observed Plasma Concentration (Tmax)
timeFrame: 24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days)
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC [0-24])
timeFrame: 24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days)
measure: Trough Plasma Concentration (Ctrough)
timeFrame: 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)
measure: Metabolite to Parent Ratio for Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC [0-24])
timeFrame: 24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days)
Other outcomes:
Locations:
city: West Hollywood
country: United States
state: California
city: Louisville
country: United States
state: Kentucky
city: Portland
country: United States
state: Oregon
city: Myrtle Beach
country: United States
state: South Carolina
city: Vancouver
country: Canada
state: British Columbia
city: Montreal
country: Canada
state: Quebec
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Saad F, Chi KN, Shore ND, Graff JN, Posadas EM, Lattouf JB, Espina BM, Zhu E, Yu A, Hazra A, De Meulder M, Mamidi RNVS, Bradic B, Francis P, Hayreh V, Rezazadeh Kalebasty A. Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE). Cancer Chemother Pharmacol. 2021 Jul;88(1):25-37. doi: 10.1007/s00280-021-04249-7. Epub 2021 Mar 22.