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

July 16, 2020 updated by: Janssen Research & Development, LLC

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

34

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada
    • Quebec
      • Montreal, Quebec, Canada
  • United States
    • California
      • West Hollywood, California, United States
    • Kentucky
      • Louisville, Kentucky, United States
    • Oregon
      • Portland, Oregon, United States
    • South Carolina
      • Myrtle Beach, South Carolina, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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).

What is the study measuring?

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
Time Frame: 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).
Up to 56 days
Number of Participants With Incidence and Severity of Adverse Events (Part 2)
Time Frame: 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.
Up to 30 days after last dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Observed Plasma Concentration (Cmax)
Time Frame: 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.
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 Frame: 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.
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])
Time Frame: 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.
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)
Time Frame: 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.
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])
Time Frame: 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.
24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Janssen Research & Development, LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 3, 2016

Primary Completion (Actual)

July 18, 2019

Study Completion (Actual)

July 19, 2019

Study Registration Dates

First Submitted

October 4, 2016

First Submitted That Met QC Criteria

October 4, 2016

First Posted (Estimate)

October 5, 2016

Study Record Updates

Last Update Posted (Actual)

July 20, 2020

Last Update Submitted That Met QC Criteria

July 16, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR108230
  • 2016-002694-35 (EudraCT Number)
  • 64091742PCR1001 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe