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

Phase 1

Terminated

• Conditions: Prostatic Neoplasms
• Interventions: Drug: EPI-7386; Drug: Abiraterone Acetate; Drug: Apalutamide; Drug: Prednisone or Prednisolone

• Registration Number: NCT05295927
• Lead Sponsor: Janssen Research & Development, LLC

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2022-03-23
• Study First Submitted: 2022-03-24
• Study First Submitted QC: 2022-03-24
• Study First Posted: 2022-03-25
• Primary Completion: 2022-09-30
• Study Completion: 2022-09-30
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-08
• Last Update Posted: 2023-05-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Group A: EPI-7386 + Abiraterone Acetate Plus Prednisone (AAP)	EPI-7386	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.
Group A: EPI-7386 + Abiraterone Acetate Plus Prednisone (AAP)	Abiraterone Acetate	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.
Group A: EPI-7386 + Abiraterone Acetate Plus Prednisone (AAP)	Prednisone or Prednisolone	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.
Group B: EPI-3786 + Apalutamide	EPI-7386	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.
Group B: EPI-3786 + Apalutamide	Apalutamide	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants with Dose-limiting Toxicities (DLT)	Up to 28 days of Cycle 1 (each cycle of 28 days)	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	At 12 weeks	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.
Number of Participants with Adverse Events (AEs)	Up to 3 Years 3 Months	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	Up to 3 Years 3 Months	Number of participants with AEs by severity will be reported.

Secondary Outcome Measures

Name	Time	Method
Minimum Observed Serum Concentration (Cmin) of EPI-7386 and Abiraterone	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)	Cmin is the minimum observed serum concentration of EPI-7386 and abiraterone.
Observed Accumulation Index Based on Cmax (ARCmax) of EPI-7386 and Abiraterone	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)	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	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)	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	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)	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	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)	Tmax is defined as the time to reach maximum observed serum concentration of EPI-7386 and apalutamide.
Observed Accumulation Index Based on Cmax (ARCmax) of EPI-7386 and Apalutamide	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)	The observed accumulation ratio for Cmax, determined after multiple dose administration EPI-7386 and apalutamide (C2D1/C1D1 and C3D1/C1D1).
Area Under the Curve From Time Zero to tau (AUC[0-tau]) of EPI-7386 and Apalutamide	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)	AUC(0-tau) is defined as area under the curve from time 0 to tau hours post dose of EPI-7386 and apalutamide.
Maximum Observed Serum Concentration (Cmax) of EPI-7386 and Abiraterone	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)	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	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)	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	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)	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 Apalutamide	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)	Cmin is the minimum observed serum concentration of EPI-7386 and apalutamide.
Accumulation Ratio for AUCtau (AR AUCtau) of EPI-7386 and Apalutamide	Day 1 of each cycle up to 3 cycles (each cycle of 28 days)	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)	Up to 3 Years 3 Months	Serum PSA concentration will be measured.

Trial Locations

Locations (4)

GU Research Network; 🇺🇸 Omaha, Nebraska, United States

Chesapeake Urology Research Associates; 🇺🇸 Towson, Maryland, United States

Carolina Urologic Research Center; 🇺🇸 Myrtle Beach, South Carolina, United States

Prostate Cancer Centre; 🇨🇦 Calgary, Alberta, Canada