Clinical trial NCT05295927: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Prostatic Neoplasms
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2022-03-25
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 3 Years 3 Months
measure: Number of Participants with AEs by Severity
timeFrame: Up to 3 Years 3 Months
measure: Number of Participants with Dose-limiting Toxicities (DLT)
timeFrame: Up to 28 days of Cycle 1 (each cycle of 28 days)
measure: Composite Response Rate
timeFrame: At 12 weeks
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of EPI-7386 and Abiraterone
timeFrame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of EPI-7386 and Abiraterone
timeFrame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
measure: Area Under the Curve From Time Zero to tau (AUC[0-tau]) of EPI-7386 and Abiraterone
timeFrame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
measure: Minimum Observed Serum Concentration (Cmin) of EPI-7386 and Abiraterone
timeFrame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
measure: Observed Accumulation Index Based on Cmax (ARCmax) of EPI-7386 and Abiraterone
timeFrame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
measure: Accumulation Ratio for AUCtau (AR AUCtau) of EPI-7386 and Abiraterone
timeFrame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
measure: Maximum Observed Serum Concentration (Cmax) of EPI-7386 and Apalutamide
timeFrame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of EPI-7386 and apalutamide
timeFrame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
measure: Area Under the Curve From Time Zero to tau (AUC[0-tau]) of EPI-7386 and Apalutamide
timeFrame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
measure: Minimum Observed Serum Concentration (Cmin) of EPI-7386 and Apalutamide
timeFrame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
measure: Observed Accumulation Index Based on Cmax (ARCmax) of EPI-7386 and Apalutamide
timeFrame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
measure: Accumulation Ratio for AUCtau (AR AUCtau) of EPI-7386 and Apalutamide
timeFrame: Day 1 of each cycle up to 3 cycles (each cycle of 28 days)
measure: Serum Prostate-Specific Antigen (PSA)
timeFrame: Up to 3 Years 3 Months
Other outcomes:
Locations:
city: Towson
country: United States
facility: Chesapeake Urology Research Associates
state: Maryland
city: Omaha
country: United States
facility: GU Research Network
state: Nebraska
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Calgary
country: Canada
facility: Prostate Cancer Centre
state: Alberta
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: