A Study of EPI-7386 in Combination With Abiraterone Acetate Plus Prednisone, or Apalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC)

Prostatic Neoplasms Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05295927
• Other study ID #: CR109122
• Secondary ID: 81712917PCR20012
• Status: Terminated
• Phase: Phase 1
• Start date: March 23, 2022
• Est. completion date: September 30, 2022

Study information

• Verified date: May 2023
• 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 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: September 30, 2022
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostatic Neoplasms

Intervention

Drug:
• EPI-7386
EPI-7386 will be administered orally once daily.
• Abiraterone Acetate
Abiraterone Acetate will be administered orally once daily.
• Prednisone or Prednisolone
Prednisone or Prednisolone will be administered orally twice daily.
• Apalutamide
Apalutamide will be administered orally once daily.

Locations

Country	Name	City	State
Canada	Prostate Cancer Centre	Calgary	Alberta
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	GU Research Network	Omaha	Nebraska
United States	Chesapeake Urology Research Associates	Towson	Maryland

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	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.	Up to 3 Years 3 Months
Primary	Number of Participants with AEs by Severity	Number of participants with AEs by severity will be reported.	Up to 3 Years 3 Months
Primary	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.	Up to 28 days of Cycle 1 (each cycle of 28 days)
Primary	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.	At 12 weeks
Secondary	Maximum Observed Serum Concentration (Cmax) of EPI-7386 and Abiraterone	Cmax is defined as the maximum observed serum concentration of EPI-7386 and abiraterone.	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Secondary	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.	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Secondary	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.	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Secondary	Minimum Observed Serum Concentration (Cmin) of EPI-7386 and Abiraterone	Cmin is the minimum observed serum concentration of EPI-7386 and abiraterone.	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Secondary	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).	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Secondary	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).	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Secondary	Maximum Observed Serum Concentration (Cmax) of EPI-7386 and Apalutamide	Cmax is defined as the maximum observed serum concentration of EPI-7386 and apalutamide.	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Secondary	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.	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Secondary	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.	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Secondary	Minimum Observed Serum Concentration (Cmin) of EPI-7386 and Apalutamide	Cmin is the minimum observed serum concentration of EPI-7386 and apalutamide.	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Secondary	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).	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Secondary	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).	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
Secondary	Serum Prostate-Specific Antigen (PSA)	Serum PSA concentration will be measured.	Up to 3 Years 3 Months