Back to resultsA Safety and Pharmacokinetics Study of Niraparib Plus an Androgen Receptor-Targeted Therapy in Men With Metastatic Castration-Resistant Prostate Cancer (BEDIVERE)
Primary Purpose
Prostatic Neoplasms
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Niraparib
Apalutamide
Abiraterone Acetate
Prednisone
Sponsored by
About this trial
This is an interventional treatment trial for Prostatic Neoplasms
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Niraparib + Apalutamide/[Abiraterone Acetate + Prednisone]
Arm Description
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.
Outcomes
Primary Outcome Measures
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).
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.
Secondary Outcome Measures
Maximum Observed Plasma Concentration (Cmax)
Maximum observed plasma concentration (Cmax) will be assessed.
Time to Reach the Maximum Observed Plasma Concentration (Tmax)
Time to reach the maximum plasma concentration(Tmax) will be assessed.
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.
Trough Plasma Concentration (Ctrough)
Ctrough is the minimum observed (that is, predose) plasma concentration following multiple dosing will be assessed.
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.
Full Information
NCT ID
NCT02924766
First Posted
October 4, 2016
Last Updated
July 16, 2020
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT02924766
Brief Title
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
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
October 3, 2016 (Actual)
Primary Completion Date
July 18, 2019 (Actual)
Study Completion Date
July 19, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostatic Neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Niraparib + Apalutamide/[Abiraterone Acetate + Prednisone]
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Niraparib
Other Intervention Name(s)
JNJ-64091742
Intervention Description
Participants will start with niraparib 200 mg once daily.
Intervention Type
Drug
Intervention Name(s)
Apalutamide
Other Intervention Name(s)
ARN-509
Intervention Description
Participants will receive apalutamide 240 mg (4*60 mg) once daily orally.
Intervention Type
Drug
Intervention Name(s)
Abiraterone Acetate
Other Intervention Name(s)
ZYTIGA
Intervention Description
Participants will receive 1000 mg (4*250mg) once daily.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Participants will receive 10 mg (1*5 mg twice daily).
Primary Outcome Measure Information:
Title
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
Description
RP2D will be defined as the highest dose of study drug at which less than 33 percent (%) of participants experience dose limiting toxicity (DLT).
Time Frame
Up to 56 days
Title
Number of Participants With Incidence and Severity of Adverse Events (Part 2)
Description
Number of participants will be assessed to further explore safety and antitumor activity in Part 2 (dose expansion) of study.
Time Frame
Up to 30 days after last dose
Secondary Outcome Measure Information:
Title
Maximum Observed Plasma Concentration (Cmax)
Description
Maximum observed plasma concentration (Cmax) will be assessed.
Time Frame
24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days)
Title
Time to Reach the Maximum Observed Plasma Concentration (Tmax)
Description
Time to reach the maximum plasma concentration(Tmax) will be assessed.
Time Frame
24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days)
Title
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC [0-24])
Description
Area under plasma concentration-time curve from time 0 to time 24 hours after dosing will be assessed.
Time Frame
24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days)
Title
Trough Plasma Concentration (Ctrough)
Description
Ctrough is the minimum observed (that is, predose) plasma concentration following multiple dosing will be assessed.
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)
Title
Metabolite to Parent Ratio for Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC [0-24])
Description
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.
Time Frame
24 hours postdose on Cycle 1 Day 1 up to 10 hours postdose Cycle 3 Day 1 (each cycle 28 days)
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
West Hollywood
State/Province
California
Country
United States
City
Louisville
State/Province
Kentucky
Country
United States
City
Portland
State/Province
Oregon
Country
United States
City
Myrtle Beach
State/Province
South Carolina
Country
United States
City
Vancouver
State/Province
British Columbia
Country
Canada
City
Montreal
State/Province
Quebec
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
33754187
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.
Results Reference
derived
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&parentIdentifier=CR108230&attachmentIdentifier=6859793c-4a76-466e-ad41-843b583b6c9c&fileName=CR108230_CSR_Synopsis.pdf&versionIdentifier=
Description
A Safety and Pharmacokinetics Study of Niraparib plus Androgen Receptor-Targeted Therapy (Apalutamide or Abiraterone Acetate plus Prednisone) in Men with Metastatic Castration-Resistant
Learn more about this trial
A Safety and Pharmacokinetics Study of Niraparib Plus an Androgen Receptor-Targeted Therapy in Men With Metastatic Castration-Resistant Prostate Cancer (BEDIVERE)
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