A Safety and Pharmacokinetics Study of Niraparib Plus an Androgen Receptor-Targeted Therapy in Men With Metastatic Castration-Resistant Prostate Cancer (BEDIVERE)
3 other identifiers
interventional
34
2 countries
6
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Oct 2016
Typical duration for phase_1
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 3, 2016
CompletedFirst Submitted
Initial submission to the registry
October 4, 2016
CompletedFirst Posted
Study publicly available on registry
October 5, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 18, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
July 19, 2019
CompletedJuly 20, 2020
July 1, 2020
2.8 years
October 4, 2016
July 16, 2020
Conditions
Outcome Measures
Primary Outcomes (2)
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 Outcomes (5)
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)
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)
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)
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)
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)
Study Arms (1)
Niraparib + Apalutamide/[Abiraterone Acetate + Prednisone]
EXPERIMENTALParticipants 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.
Interventions
Participants will start with niraparib 200 mg once daily.
Participants will receive apalutamide 240 mg (4\*60 mg) once daily orally.
Participants will receive 1000 mg (4\*250mg) once daily.
Participants will receive 10 mg (1\*5 mg twice daily).
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
Unknown Facility
West Hollywood, California, United States
Unknown Facility
Louisville, Kentucky, United States
Unknown Facility
Portland, Oregon, United States
Unknown Facility
Myrtle Beach, South Carolina, United States
Unknown Facility
Vancouver, British Columbia, Canada
Unknown Facility
Montreal, Quebec, Canada
Related Publications (1)
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.
PMID: 33754187DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Janssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 4, 2016
First Posted
October 5, 2016
Study Start
October 3, 2016
Primary Completion
July 18, 2019
Study Completion
July 19, 2019
Last Updated
July 20, 2020
Record last verified: 2020-07