Back to resultsA Study of EPI-7386 in Combination With Abiraterone Acetate Plus Prednisone, or Apalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC)
Primary Purpose
Prostatic Neoplasms
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
EPI-7386
Abiraterone Acetate
Prednisone or Prednisolone
Apalutamide
Sponsored by
About this trial
This is an interventional treatment trial for Prostatic Neoplasms
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed prostate adenocarcinoma
- Must be able to continue Gonadotropin-releasing hormone agonist (GnRHa) during the study if not surgically castrate
- Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1, or 2
- Must be able to swallow oral medicines
- Contraceptive use by men (and female partners of men enrolled in the study who are of childbearing potential or are pregnant) (birth control) use should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies
- Willing and able to adhere to the prohibitions and restrictions specified in this protocol
Exclusion Criteria:
- Known central nervous system (CNS) metastases
- Non-metastatic castration-resistant prostate cancer (CRPC) (biochemical or locoregional disease only) is excluded from trial participation
- Evidence of predominant neuroendocrine/small cell carcinoma features in archival or baseline tumor biopsy specimen(s)
- Symptomatic or impending spinal cord compression, except if participant has received definitive treatment and demonstrates evidence of clinically stable disease
- Known disorder affecting gastrointestinal absorption
Sites / Locations
- Chesapeake Urology Research Associates
- GU Research Network
- Carolina Urologic Research Center
- Prostate Cancer Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Group A: EPI-7386 + Abiraterone Acetate Plus Prednisone (AAP)
Group B: EPI-3786 + Apalutamide
Arm Description
Participants with metastatic castration-resistant prostate cancer (mCRPC) will receive EPI-7386 + AAP to determine the recommended phase 2 dose (RP2D) dose of EPI-7386 in combination with AAP in dose finding portion of the study. In dose expansion portion of the study, participants will receive EPI-7386 RP2D in combination with AAP.
Participants with mCRPC will receive EPI-7386 + apalutamide to determine RP2D dose of EPI-7386 in combination with apalutamide in dose finding portion of the study. In dose expansion portion of the study, participants will receive EPI-7386 RP2D in combination with apalutamide.
Outcomes
Primary Outcome Measures
Number of Participants with Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Number of Participants with AEs by Severity
Number of participants with AEs by severity will be reported.
Number of Participants with Dose-limiting Toxicities (DLT)
The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Composite Response Rate
Composite response rate at 12 weeks, defined as either 90 percent (%) reduction in prostate-specific antigen (PSA) level from baseline (PSA-90), or objective response (confirmed per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) in participants with measurable disease, or both at 12 weeks.
Secondary Outcome Measures
Maximum Observed Serum Concentration (Cmax) of EPI-7386 and Abiraterone
Cmax is defined as the maximum observed serum concentration of EPI-7386 and abiraterone.
Time to Reach Maximum Observed Serum Concentration (Tmax) of EPI-7386 and Abiraterone
Tmax is defined as the time to reach maximum observed serum concentration of EPI-7386 and abiraterone.
Area Under the Curve From Time Zero to tau (AUC[0-tau]) of EPI-7386 and Abiraterone
AUC(0-tau) is defined as area under the curve from time 0 to tau hours post dose of EPI-7386 and abiraterone.
Minimum Observed Serum Concentration (Cmin) of EPI-7386 and Abiraterone
Cmin is the minimum observed serum concentration of EPI-7386 and abiraterone.
Observed Accumulation Index Based on Cmax (ARCmax) of EPI-7386 and Abiraterone
The observed accumulation ratio for Cmax, determined after multiple dose administration of EPI-7386 and abiraterone (Cycle[C] 2 Day[D] 1/C1D1 and C3D1/C1D1).
Accumulation Ratio for AUCtau (AR AUCtau) of EPI-7386 and Abiraterone
The observed accumulation ratio for AUCtau, determined after multiple dose administration of EPI-7386 and abiraterone (C2D1/C1D1 and C3D1/C1D1).
Maximum Observed Serum Concentration (Cmax) of EPI-7386 and Apalutamide
Cmax is defined as the maximum observed serum concentration of EPI-7386 and apalutamide.
Time to Reach Maximum Observed Serum Concentration (Tmax) of EPI-7386 and apalutamide
Tmax is defined as the time to reach maximum observed serum concentration of EPI-7386 and apalutamide.
Area Under the Curve From Time Zero to tau (AUC[0-tau]) of EPI-7386 and Apalutamide
AUC(0-tau) is defined as area under the curve from time 0 to tau hours post dose of EPI-7386 and apalutamide.
Minimum Observed Serum Concentration (Cmin) of EPI-7386 and Apalutamide
Cmin is the minimum observed serum concentration of EPI-7386 and apalutamide.
Observed Accumulation Index Based on Cmax (ARCmax) of EPI-7386 and Apalutamide
The observed accumulation ratio for Cmax, determined after multiple dose administration EPI-7386 and apalutamide (C2D1/C1D1 and C3D1/C1D1).
Accumulation Ratio for AUCtau (AR AUCtau) of EPI-7386 and Apalutamide
The observed accumulation ratio for AUCtau, determined after multiple dose administration EPI-7386 and Apalutamide (C2D1/C1D1 and C3D1/C1D1).
Serum Prostate-Specific Antigen (PSA)
Serum PSA concentration will be measured.
Full Information
NCT ID
NCT05295927
First Posted
March 24, 2022
Last Updated
May 8, 2023
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT05295927
Brief Title
A Study of EPI-7386 in Combination With Abiraterone Acetate Plus Prednisone, or Apalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC)
Official Title
A Phase 1b Study of EPI-7386 in Combination With Abiraterone Acetate Plus Prednisone or Apalutamide in mCRPC (ARES: Androgen Receptor Eradication Study)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Terminated
Why Stopped
Administrative Decision
Study Start Date
March 23, 2022 (Actual)
Primary Completion Date
September 30, 2022 (Actual)
Study Completion Date
September 30, 2022 (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 Drug Product
Yes
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 determine safety, including dose limiting toxicities, and the recommended phase 2 dose (RP2D) of EPI-7386 in separate combinations with (a) abiraterone acetate plus prednisone or prednisolone (AAP) and (b) apalutamide (dose-finding) and to determine the antitumor activity of EPI-7386 in separate combinations with (a) AAP and (b) apalutamide (dose-expansion).
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
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A: EPI-7386 + Abiraterone Acetate Plus Prednisone (AAP)
Arm Type
Experimental
Arm Description
Participants with metastatic castration-resistant prostate cancer (mCRPC) will receive EPI-7386 + AAP to determine the recommended phase 2 dose (RP2D) dose of EPI-7386 in combination with AAP in dose finding portion of the study. In dose expansion portion of the study, participants will receive EPI-7386 RP2D in combination with AAP.
Arm Title
Group B: EPI-3786 + Apalutamide
Arm Type
Experimental
Arm Description
Participants with mCRPC will receive EPI-7386 + apalutamide to determine RP2D dose of EPI-7386 in combination with apalutamide in dose finding portion of the study. In dose expansion portion of the study, participants will receive EPI-7386 RP2D in combination with apalutamide.
Intervention Type
Drug
Intervention Name(s)
EPI-7386
Intervention Description
EPI-7386 will be administered orally once daily.
Intervention Type
Drug
Intervention Name(s)
Abiraterone Acetate
Intervention Description
Abiraterone Acetate will be administered orally once daily.
Intervention Type
Drug
Intervention Name(s)
Prednisone or Prednisolone
Intervention Description
Prednisone or Prednisolone will be administered orally twice daily.
Intervention Type
Drug
Intervention Name(s)
Apalutamide
Intervention Description
Apalutamide will be administered orally once daily.
Primary Outcome Measure Information:
Title
Number of Participants with Adverse Events (AEs)
Description
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Time Frame
Up to 3 Years 3 Months
Title
Number of Participants with AEs by Severity
Description
Number of participants with AEs by severity will be reported.
Time Frame
Up to 3 Years 3 Months
Title
Number of Participants with Dose-limiting Toxicities (DLT)
Description
The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Time Frame
Up to 28 days of Cycle 1 (each cycle of 28 days)
Title
Composite Response Rate
Description
Composite response rate at 12 weeks, defined as either 90 percent (%) reduction in prostate-specific antigen (PSA) level from baseline (PSA-90), or objective response (confirmed per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) in participants with measurable disease, or both at 12 weeks.
Time Frame
At 12 weeks
Secondary Outcome Measure Information:
Title
Maximum Observed Serum Concentration (Cmax) of EPI-7386 and Abiraterone
Description
Cmax is defined as the maximum observed serum concentration of EPI-7386 and abiraterone.
Time Frame
Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Title
Time to Reach Maximum Observed Serum Concentration (Tmax) of EPI-7386 and Abiraterone
Description
Tmax is defined as the time to reach maximum observed serum concentration of EPI-7386 and abiraterone.
Time Frame
Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Title
Area Under the Curve From Time Zero to tau (AUC[0-tau]) of EPI-7386 and Abiraterone
Description
AUC(0-tau) is defined as area under the curve from time 0 to tau hours post dose of EPI-7386 and abiraterone.
Time Frame
Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Title
Minimum Observed Serum Concentration (Cmin) of EPI-7386 and Abiraterone
Description
Cmin is the minimum observed serum concentration of EPI-7386 and abiraterone.
Time Frame
Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Title
Observed Accumulation Index Based on Cmax (ARCmax) of EPI-7386 and Abiraterone
Description
The observed accumulation ratio for Cmax, determined after multiple dose administration of EPI-7386 and abiraterone (Cycle[C] 2 Day[D] 1/C1D1 and C3D1/C1D1).
Time Frame
Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Title
Accumulation Ratio for AUCtau (AR AUCtau) of EPI-7386 and Abiraterone
Description
The observed accumulation ratio for AUCtau, determined after multiple dose administration of EPI-7386 and abiraterone (C2D1/C1D1 and C3D1/C1D1).
Time Frame
Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Title
Maximum Observed Serum Concentration (Cmax) of EPI-7386 and Apalutamide
Description
Cmax is defined as the maximum observed serum concentration of EPI-7386 and apalutamide.
Time Frame
Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Title
Time to Reach Maximum Observed Serum Concentration (Tmax) of EPI-7386 and apalutamide
Description
Tmax is defined as the time to reach maximum observed serum concentration of EPI-7386 and apalutamide.
Time Frame
Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Title
Area Under the Curve From Time Zero to tau (AUC[0-tau]) of EPI-7386 and Apalutamide
Description
AUC(0-tau) is defined as area under the curve from time 0 to tau hours post dose of EPI-7386 and apalutamide.
Time Frame
Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Title
Minimum Observed Serum Concentration (Cmin) of EPI-7386 and Apalutamide
Description
Cmin is the minimum observed serum concentration of EPI-7386 and apalutamide.
Time Frame
Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Title
Observed Accumulation Index Based on Cmax (ARCmax) of EPI-7386 and Apalutamide
Description
The observed accumulation ratio for Cmax, determined after multiple dose administration EPI-7386 and apalutamide (C2D1/C1D1 and C3D1/C1D1).
Time Frame
Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Title
Accumulation Ratio for AUCtau (AR AUCtau) of EPI-7386 and Apalutamide
Description
The observed accumulation ratio for AUCtau, determined after multiple dose administration EPI-7386 and Apalutamide (C2D1/C1D1 and C3D1/C1D1).
Time Frame
Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Title
Serum Prostate-Specific Antigen (PSA)
Description
Serum PSA concentration will be measured.
Time Frame
Up to 3 Years 3 Months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed prostate adenocarcinoma
Must be able to continue Gonadotropin-releasing hormone agonist (GnRHa) during the study if not surgically castrate
Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1, or 2
Must be able to swallow oral medicines
Contraceptive use by men (and female partners of men enrolled in the study who are of childbearing potential or are pregnant) (birth control) use should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies
Willing and able to adhere to the prohibitions and restrictions specified in this protocol
Exclusion Criteria:
Known central nervous system (CNS) metastases
Non-metastatic castration-resistant prostate cancer (CRPC) (biochemical or locoregional disease only) is excluded from trial participation
Evidence of predominant neuroendocrine/small cell carcinoma features in archival or baseline tumor biopsy specimen(s)
Symptomatic or impending spinal cord compression, except if participant has received definitive treatment and demonstrates evidence of clinically stable disease
Known disorder affecting gastrointestinal absorption
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:
Facility Name
Chesapeake Urology Research Associates
City
Towson
State/Province
Maryland
ZIP/Postal Code
21204
Country
United States
Facility Name
GU Research Network
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68130
Country
United States
Facility Name
Carolina Urologic Research Center
City
Myrtle Beach
State/Province
South Carolina
ZIP/Postal Code
29572
Country
United States
Facility Name
Prostate Cancer Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2V 1P9
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency
Learn more about this trial
A Study of EPI-7386 in Combination With Abiraterone Acetate Plus Prednisone, or Apalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC)
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