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

Prostatic Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02924766
• Other study ID #: CR108230
• Secondary ID: 2016-002694-3564
• Status: Completed
• Phase: Phase 1
• Start date: October 3, 2016
• Est. completion date: July 19, 2019

Study information

• Verified date: July 2020
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: July 19, 2019
• Est. primary completion date: July 18, 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostatic Neoplasms

Intervention

Drug:
• Niraparib
Participants will start with niraparib 200 mg once daily.
• Apalutamide
Participants will receive apalutamide 240 mg (4*60 mg) once daily orally.
• Abiraterone Acetate
Participants will receive 1000 mg (4*250mg) once daily.
• Prednisone
Participants will receive 10 mg (1*5 mg twice daily).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)

External Links

•   A Safety and Pharmacokinetics Study of Niraparib plus Androgen Receptor-Targeted Therapy (Apalutamide or Abiraterone Acetate plus Prednisone) in Men with Metastatic Castration-Resistant