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

NCT05295927 | Terminated Phase 1 FDA Drug

• 3 other identifiers: CR10912281712917PCR20012022-000946-14
• Study Type: interventional
• Target: 3
• Locations: 2 countries
• Sites: 4

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).

Conditions

Prostatic Neoplasms

Outcome Measures

Primary Outcomes (4)

• 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

• Number of Participants with AEs by Severity

  Number of participants with AEs by severity will be reported.

  Up to 3 Years 3 Months

• 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)

• 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 Outcomes (13)

• Maximum Observed Serum Concentration (Cmax) of EPI-7386 and Abiraterone

  Day 1 of each cycle up to 3 cycles (each cycle of 28 days)

• 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)

• 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)

• Minimum Observed Serum Concentration (Cmin) of EPI-7386 and Abiraterone

  Day 1 of each cycle up to 3 cycles (each cycle of 28 days)

• 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)

Study Arms (2)

Group A: EPI-7386 + Abiraterone Acetate Plus Prednisone (AAP)

EXPERIMENTAL

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.

Drug: EPI-7386; Drug: Abiraterone Acetate; Drug: Prednisone or Prednisolone

Group B: EPI-3786 + Apalutamide

EXPERIMENTAL

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.

Drug: EPI-7386; Drug: Apalutamide

Interventions

EPI-7386 DRUG

EPI-7386 will be administered orally once daily.

Group A: EPI-7386 + Abiraterone Acetate Plus Prednisone (AAP); Group B: EPI-3786 + Apalutamide

Abiraterone Acetate DRUG

Abiraterone Acetate will be administered orally once daily.

Group A: EPI-7386 + Abiraterone Acetate Plus Prednisone (AAP)

Prednisone or Prednisolone DRUG

Prednisone or Prednisolone will be administered orally twice daily.

Group A: EPI-7386 + Abiraterone Acetate Plus Prednisone (AAP)

Apalutamide DRUG

Apalutamide will be administered orally once daily.

Group B: EPI-3786 + Apalutamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (4)

Chesapeake Urology Research Associates

Towson, Maryland, 21204, United States

Location

GU Research Network

Omaha, Nebraska, 68130, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Prostate Cancer Centre

Calgary, Alberta, T2V 1P9, Canada

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abiraterone Acetate; Prednisone; Prednisolone; apalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Pregnadienetriols

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2022
• First Posted: March 25, 2022
• Study Start: March 23, 2022
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: February 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

US (3); CA (1)