Combining EPI-7386 With Enzalutamide and Androgen Deprivation Therapy for Metastatic Hormone-Sensitive Prostate Cancer

NCT ID: NCT06312670

Last Updated: 2025-05-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-16
• Study Completion Date: 2025-01-09

Brief Summary

The purpose of this study is to study the effects of EPI-7386 in combination with Enzalutamide on participants diagnosed with prostate cancer. The main goals of this study are to evaluate the antitumor activity of EPI-7386 in combination with enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC), and to evaluate the pharmacokinetics (PK) of EPI-7386 when dosed in combination with enzalutamide. Participants will will take the study drug, EPI-7360, twice a day by mouth and enzalutamide once a day by mouth, alongside clinic visits every two weeks.

Detailed Description

EPI-7386 is an investigational drug that works by blocking the androgen receptor at a different site compared to the approved androgen receptor blockers. This may increase the effectiveness of this drug and increase the effectiveness of approved androgen receptor blockers when taken together. EPI-7386 is a new drug; therefore, its effectiveness and safety in prostate cancer patients must be studied before it is approved by the Food and Drug Administration. EPI-7386 is experimental because it is not currently approved by the Food and Drug Administration (FDA). Enzalutamide is approved by the FDA for patients whose prostate cancers has spread after receiving treatment. The hypothesis is that adding EPI-7386 to standard hormone therapy will be more effective in treating cancer compared to usual treatment, with the long term goal of discovering more about hormone therapy as a treatment for cancer.

Conditions

Metastatic Hormone-sensitive Prostate Cancer (mHSPC); Prostate Cancer; Prostate Adenocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

EPI-7386 + Enzalutamide

EPI-7386 at 600 mg twice daily orally with standard of care Enzalutamide at 160 mg, once daily, orally for 36 months of treatment (11 cycles).

Group Type: EXPERIMENTAL

EPI-7386

Intervention Type: DRUG

600 mg orally administered twice daily

Enzalutamide

Intervention Type: DRUG

160 mg administered orally once daily, with or without food

Androgen Deprivation Therapy (ADT)

Intervention Type: DRUG

LHRH agonist/antagonist or orchiectomy

Interventions

EPI-7386

600 mg orally administered twice daily

Intervention Type: DRUG

Enzalutamide

160 mg administered orally once daily, with or without food

Intervention Type: DRUG

Androgen Deprivation Therapy (ADT)

LHRH agonist/antagonist or orchiectomy

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjects must have histologically or cytologically confirmed prostate adenocarcinoma without small cell or neuroendocrine features (please note: >10% small cell or neuroendocrine differentiation will be excluded).
• Subjects must have received no prior second-generation antiandrogen therapies for this disease. Androgen deprivation with LHRH agonist/antagonist therapy or history of bilateral orchiectomy that started less than 12 weeks before study enrollment is allowed.
• Subjects may have either de novo or recurrent metastatic disease. Presence of metastatic disease at study entry documented by 1 or more lesions - bone, lymph node, soft tissue, or visceral metastases - observed by any imaging technique.
• Age >18 years. This study will be limited to adults only.
• Evidence of metastatic disease by conventional CT of chest, abdomen, and pelvis, and bone scans, OR Positron emission tomography (PET) scan, OR MRI.
• ECOG performance status of 0 to 2.
• Subjects must have normal organ and marrow function as defined below:

• Absolute neutrophil count >1000/μL; platelet count >100 000/μL; hemoglobin >8.5 g/dL) at screening. Note: Subjects must not have received any growth factors within 7 days or blood transfusions within 14 days prior to the hematologic laboratory values obtained at screening).
• Total bilirubin (TBIL) <2 × the upper limit of normal (ULN) at screening, except subjects with documented Gilbert syndrome who must have a TBIL <3 mg/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <5 × ULN at screening
• Creatinine clearance ≥45 mL/min and/or estimated glomerular filtration rate (eGFR) ≥30
• Albumin >30 g/L (3.0 g/dL) at screening
• Subjects receiving bisphosphonates or other approved bone-targeting therapy (e.g., denosumab) must be on a stable dose for at least 28 days before the start of study treatment.
• Radiation therapy is allowed at any time, as deemed appropriate by the treating investigator.
• Subjects of child-producing potential agree to use highly effective contraceptive methods (i.e., barrier contraception measures such as a male condom with spermicide during intercourse) and avoid sperm donation during the study treatment and for 3 months after the last dose of study treatment. A man is considered to be of child-producing potential, unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy. Partners of participants must also practice approved forms of birth control.
• Subjects must have the ability to understand and the willingness to sign a written informed consent form (ICF).
• Members of all races and ethnic groups are eligible for this trial. At least ≥ 20% of enrolled subjects must be of African American descent. (self-reported).

Exclusion Criteria

• Evidence of mCRPC.
• Receipt of any other investigational agents.
• 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 noninvasive malignancies, as determined by the PI or CoPI.
• Gastrointestinal issues affecting absorption (e.g., gastrectomy).
• Known history of seizure or conditions that may predispose the subject to seizure, including brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, or brain arteriovenous malformation. Subjects with brain metastases/central nervous system (CNS) disease that are treated prior to enrollment will be allowed in this clinical trial.
• Known or suspected hypersensitivity to any components of the formulation used for EPI-7386 or enzalutamide.
• Use of compounds known to be strong inducers of CYP3A within 30 days prior to start of study drug treatment, and strong inhibitors of CYP2C8 within 14 days of the first dose of study treatment.
• Use of narrow therapeutic index sensitive CYP2C8 substrates (e.g., daprobustat, dasabuvir, repaglinide, paclitaxel) or sensitive substrates for CYP3A.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations considered by the Investigator to limit compliance with study requirements.

• Minimum Eligible Age: 19 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

ESSA Pharma Inc.

UNKNOWN

Sponsor Role: collaborator

Pedro Barata, MD, MSc

OTHER

Sponsor Role: lead

Responsible Party

Pedro Barata, MD, MSc

Director, Clinical Genitourinary Medical Oncology Research Program, Prinicipal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Pedro Barata, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Christopher Wee, MD

Role: PRINCIPAL_INVESTIGATOR

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Locations

University Hospitals Cleveland Medical Center Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

CASE2823

Identifier Type: -

Identifier Source: org_study_id