EPI-7386 in Combination With Enzalutamide Compared With Enzalutamide Alone in Subjects With mCRPC

Prostate Cancer Clinical Trial

Official title:

A Phase 1/2 Study of EPI-7386 in Combination With Enzalutamide Compared With Enzalutamide Alone in Subjects With Metastatic Castration-Resistant Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05075577
• Other study ID #: EPI-7386-CS-010
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 21, 2021
• Est. completion date: January 2026

Study information

• Verified date: February 2024
• Source: ESSA Pharmaceuticals
• Contact: Karen Villaluna
• Phone: 650-449-8400
• Email: kvillaluna[@]essapharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1/2 study of EPI-7386 orally administered in combination with enzalutamide in subjects with mCRPC. Phase 1 of the study will be a single-arm dose escalation study of EPI-7386 in combination with a fixed dose of enzalutamide. This portion of the study will primarily evaluate the safety and tolerability of the drug combination and establish the RP2CDs for EPI-7386 and enzalutamide when dosed in combination. In addition, blood sampling will be conducted for PK evaluation to assess the potential DDI between the two drugs. Once the RP2CD for each drug has been established, Phase 2 of the study will commence. Phase 2 is a two-arm, randomized (2:1), open-label study. Approximately 120 subjects will be randomized 2:1 to: - Group 1: EPI-7386 at the RP2CD + enzalutamide(depending on the results of the Phase 1) (n=80) - Group 2: Enzalutamide single agent (n=40) The planned dose of enzalutamide and EPI-7386 for the combination arm will be those determined in the Phase 1 of this study based on safety and exposure data. Subjects may remain on study treatment as long as they are tolerating treatment without disease progression based on RECIST v1.1 and/or PCWG3.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: January 2026
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Males =18 years.
• Histologically, pathologically, or cytologically confirmed prostate adenocarcinoma.
• Evidence of castration-resistant prostate cancer (CRPC).
• Presence of metastatic disease at study entry documented by 1 or more bone lesions on bone scan or by soft tissue disease observed by CT/MRI.
• Naïve to second generation anti-androgens.
• Evidence of progressive disease defined as 1 or more Prostate Cancer Working Group 3 (PCWG3) criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Ongoing ADT with luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy or history of bilateral orchiectomy, with castrate level testosterone.
• Serum testosterone =1.73 nmol/L (50 ng/dL).
• Subjects receiving bisphosphonates or other approved bone-targeting therapy (e.g., denosumab) must be on a stable dose for at least 28 days prior to the start of study treatment.
• Demonstrate adequate organ function.

Exclusion Criteria:

• Biologic anti-cancer therapy within 28 days prior to the start of study treatment.
• Use of hormonal agents with anti-tumor activity against prostate cancer within 28 days prior to the start of study treatment.
• Use of herbal products or alternative therapies that may decrease PSA levels or that may have hormonal anti-prostate cancer activity within 28 days prior to the start of study treatment or plans to initiate during the study.
• Intervention with any chemotherapy, investigational agents, or other anti-cancer drugs within 28 days of the first dose of study treatment.
• Use of radium-223 dichloride or other radioligand/radiopharmaceutical within 28 days prior to the start of study treatment.
• Received limited-field palliative bone radiotherapy >5 fractions and/or any radiotherapy within 2 weeks prior to the start of study treatment.
• Received a blood transfusion within 28 days of hematologic screening labs.
• Known intra-cerebral disease or brain metastasis unless adequately treated and stable for the last 28 days before signing of informed consent.
• Spinal cord compression.
• Diagnosis of another clinically significant malignancy within the previous 3 years other than curatively treated non-melanomatous skin cancer or superficial urothelial carcinoma and other in situ or non-invasive malignancies.
• Gastrointestinal issues affecting absorption.
• Significant cardiovascular disease.
• Known history of seizure or conditions that may pre-dispose them to seizure, including brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, and brain arteriovenous malformation.
• Concurrent disease or any clinically significant abnormality.
• Known or suspected hypersensitivity to any components of the formulation used for EPI-7386 or enzalutamide.
• Use of strong inhibitors of CYP2C8.
• Use of strong inducers of CYP3A.
• Use of narrow therapeutic index sensitive CYP2C8 or sensitive substrates for CYP3A and CYP2B6.
• Use of granulocyte colony stimulating factor within 7 days prior to screening laboratories.
• Not a candidate for enzalutamide treatment.
• Patients with rare hereditary problems of fructose intolerance.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Enzalutamide
Daily oral dose of enzalutamide
• EPI-7386 with Enzalutamide
Daily oral dose of EPI-7386 in combination of enzalutamide

Locations

Country	Name	City	State
Australia	Eastern Health	Box Hill	Victoria
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	St. Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	The Canberra Hospital	Garran	Australian Capital Territory
Canada	Prostate Cancer Centre	Calgary	Alberta
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Juravinski Cancer Centre, Hamilton, ON L8V 5C2	Hamilton	Ontario
Canada	Centre Hospitalier de l'Universite de Montreal	Montréal	Quebec
Canada	Jewish General Hospital	Montréal	Quebec
Canada	Princess Margaret Cancer Center	Toronto	Ontario
United States	Chesapeake Urology Associates	Baltimore	Maryland
United States	Johns Hopkins University	Baltimore	Maryland
United States	Great Lakes Cancer Center	Buffalo	New York
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	University of Wisconsin	Madison	Wisconsin
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Urology Cancer Center	Omaha	Nebraska
United States	Hematology Oncology Associates of the Treasure Coast	Port Saint Lucie	Florida
United States	OHSU Knight Cancer Instititue	Portland	Oregon
United States	Washington University Siteman Cancer Center	Saint Louis	Missouri
United States	Moffitt Cancer Center	Tampa	Florida
United States	Arizona Urology	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
ESSA Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Incidence of Dose Limiting Toxicities	Characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for AEs [NCI CTCAE version 5.0]), timing in relation to study treatment administration, seriousness, and relationship to study treatment.	Baseline to End of Cycle 1 (each cycle is 28 days)
Primary	Phase 1: Incidence of treatment emergent adverse events	Characterized by type, frequency, severity, timing, seriousness, and relationship to study treatment.	Baseline to 30 days after last dose of study drug
Primary	Phase 1: Incidence of laboratory abnormalities as a measure of safety and tolerability of EPI-7386	Characterized by type, frequency, severity, timing, seriousness, and relationship to study treatment.	Baseline to 30 days after last dose of study drug
Primary	Phase 1: Changes in ECOG performance status		Baseline to 30 days after last dose of study drug
Primary	Phase 2: Proportion of subjects with a prostate-specific antigen decline of >50% (PSA50) at Week 12		Baseline to Week 12