EPI-7386 in Combination with Enzalutamide Compared with E... | NCT05075577

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Phase 1 Cohort 1	Experimental	600 mg QD EPI-7386 in combination of Enzalutamide120 mg	Drug: EPI-7386 with Enzalutamide
Phase 1 Cohort 2	Experimental	800 mg QD EPI-7386 in combination of Enzalutamide120 mg	Drug: EPI-7386 with Enzalutamide
Phase 1 Cohort 3	Experimental	600 mg BID EPI-7386 in combination of Enzalutamide120 mg	Drug: EPI-7386 with Enzalutamide
Phase 1 Cohort 4	Experimental	RP2D mg EPI-7386 in combination of Enzalutamide160 mg	Drug: EPI-7386 with Enzalutamide
Phase 2 Enzalutamide + EPI-7386 (Randomized 2:1)	Experimental	RP2D mg EPI-7386 in combination of Enzalutamide RP2D mg	Drug: EPI-7386 with Enzalutamide
Phase 2 Enzalutamide single agent	Active Comparator	Enzalutamide 160 mg

Name	Type	Description	Arm Group Labels	Other Names
Enzalutamide	Drug	Daily oral dose of enzalutamide	Phase 2 Enzalutamide single agent

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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)
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
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
Phase 1: Changes in ECOG performance status		Baseline to 30 days after last dose of study drug
Phase 2: Proportion of subjects with a prostate-specific antigen decline of >90% (PSA90) at Week 12		Baseline to Week 12

Eligibility Module

Eligibility Criteria

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.

Facility	Status	City	State	ZIP	Country	Contacts
Arizona Urology		Tucson	Arizona	85741	United States
Hematology Oncology Associates of the Treasure Coast

ID	Term
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D011469	Prostatic Diseases
D052801	Male Urogenital Diseases