Oral EPI-7386 in Patients with Castration-Resistant Prostate Cancer

NCT ID: NCT04421222

Last Updated: 2025-02-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-23
• Study Completion Date: 2024-12-03

Brief Summary

This is a phase I, clinical research study of EPI-7386, an investigational drug being studied as a treatment for patients with prostate cancer. All patients in the study will receive EPI-7386.

Since this is the first study of EPI-7386 in humans, there is no information about how it affects people or what dose should be used. Therefore, the main purpose of this study is to assess the safety (side effects) of EPI-7386 and to find a dose that can be given without unacceptable side effects.

There are other important things that will be evaluated during the study:

• How the amount of EPI-7386 in the blood changes over time.
• The effect of EPI-7386 on prostate cancer.
• The effect of EPI-7386 on certain substances in the body.
• The possibility that EPI-7386 can interact with other drugs.

The study will be conducted in 2 parts:

• Part A: To evaluate the safety and tolerability of EPI-7386 as a single agent via 2 Phases:

• Phase 1a: Dose Escalation (mCRPC)
• Phase 1b: Dose Expansion (mCRPC)
• Part B: To evaluate 2 parallel enrolling cohorts (Cohort 1 and Cohort 2) of EPI-7386 in combination of apalutamide acetate + prednisone (AAP) or apalutamide (APA):

• Cohort 1: Combination with AAP in mHSPC or mCRPC patients
• Cohort 2: Will evaluate the anti-tumor activity of EPI-7386 for a limited window of time (12 weeks EPI-7386 monotherapy prior to the start of combination therapy with APA) in nmCRPC patients unperturbed by previous 2nd generation anti-androgen therapies or chemotheraphy.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A/Phase 1a: Cohort 1 (Completed)

200 mg EPI-7386

Group Type: EXPERIMENTAL

EPI-7386 (QD)

Intervention Type: DRUG

Once daily oral dose of EPI-7386

Part A/Phase 1a: Cohort 2 (Completed)

400 mg EPI-7386

Group Type: EXPERIMENTAL

EPI-7386 (QD)

Intervention Type: DRUG

Once daily oral dose of EPI-7386

Part A/Phase 1a: Cohort 3 (Completed)

600 mg EPI-7386

Group Type: EXPERIMENTAL

EPI-7386 (QD)

Intervention Type: DRUG

Once daily oral dose of EPI-7386

Part A/Phase 1a: Cohort 4 (Completed)

800 mg EPI-7386

Group Type: EXPERIMENTAL

EPI-7386 (QD)

Intervention Type: DRUG

Once daily oral dose of EPI-7386

Part A/Phase 1a: Cohort 5 (Completed)

1000 mg EPI-7386

Group Type: EXPERIMENTAL

EPI-7386 (QD)

Intervention Type: DRUG

Once daily oral dose of EPI-7386

Part A/Phase 1a: Cohort 6 (Completed)

800 mg EPI-7386

Group Type: EXPERIMENTAL

EPI-7386 (BID)

Intervention Type: DRUG

Twice daily oral dose of EPI-7386

Part A/Phase 1a: Cohort 7 (Completed)

1200 mg EPI-7386

Group Type: EXPERIMENTAL

EPI-7386 (BID)

Intervention Type: DRUG

Twice daily oral dose of EPI-7386

Part A/Phase 1b: Cohort 1 (Completed)

600 mg EPI-7386 BID

Group Type: EXPERIMENTAL

EPI-7386 (BID)

Intervention Type: DRUG

Twice daily oral dose of EPI-7386

Part A/Phase 1b: Cohort 2

600 mg EPI-7386 QD

Group Type: EXPERIMENTAL

EPI-7386 (QD)

Intervention Type: DRUG

Once daily oral dose of EPI-7386

Part B/Cohort 1a

600 mg EPI-7386 + 1000 mg Abiraterone Acetate + Prednisone

Group Type: EXPERIMENTAL

EPI-7386 (QD)

Intervention Type: DRUG

Once daily oral dose of EPI-7386

Abiraterone acetate

Intervention Type: DRUG

Once daily dose of abiraterone acetate

Part B/Cohort 1b

800 mg EPI-7386 + 1000 mg Abiraterone Acetate + Prednisone

Group Type: EXPERIMENTAL

EPI-7386 (QD)

Intervention Type: DRUG

Once daily oral dose of EPI-7386

Abiraterone acetate

Intervention Type: DRUG

Once daily dose of abiraterone acetate

Part B/Cohort 1c

1200 mg EPI-7386 + 1000 mg Abiraterone Acetate + Prednisone

Group Type: EXPERIMENTAL

EPI-7386 (BID)

Intervention Type: DRUG

Twice daily oral dose of EPI-7386

Abiraterone acetate

Intervention Type: DRUG

Once daily dose of abiraterone acetate

Part B/Cohort 2a

600 mg EPI-7386 monotherapy for 12 weeks then 600 mg EPI-7386 + 240 mg Apalutamide

Group Type: EXPERIMENTAL

EPI-7386 (QD)

Intervention Type: DRUG

Once daily oral dose of EPI-7386

Apalutamide

Intervention Type: DRUG

Once daily dose of apalutamide

Part B/Cohort 2b

800 mg EPI-7386 monotherapy for 12 weeks then 800 mg EPI-7386 + 240 mg Apalutamide

Group Type: EXPERIMENTAL

EPI-7386 (QD)

Intervention Type: DRUG

Once daily oral dose of EPI-7386

Apalutamide

Intervention Type: DRUG

Once daily dose of apalutamide

Part B/Cohort 2c

1200 mg EPI-7386 monotherapy for 12 weeks then 1200 mg EPI-7386 + 240 mg Apalutamide

Group Type: EXPERIMENTAL

EPI-7386 (BID)

Intervention Type: DRUG

Twice daily oral dose of EPI-7386

Apalutamide

Intervention Type: DRUG

Once daily dose of apalutamide

Interventions

EPI-7386 (QD)

Once daily oral dose of EPI-7386

Intervention Type: DRUG

EPI-7386 (BID)

Twice daily oral dose of EPI-7386

Intervention Type: DRUG

Abiraterone acetate

Once daily dose of abiraterone acetate

Intervention Type: DRUG

Apalutamide

Once daily dose of apalutamide

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male 18 years of age or older.
• Histologically, pathologically, or cytologically confirmed prostate cancer without small cell features.
• 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.
• Limited further treatment options available known to confer clinical benefit in this disease setting from the perspective of the treating physician. Specifically, patients must have progressed on at least 2, but not more than 3, prior approved systemic therapies for mCRPC which include at least one, but not more than 2, second generation anti-androgen drug.
• Patients may have received prior docetaxel for mCSPC or mCRPC but must not have had disease progression during, or within 6 months of completing chemotherapy. Only one line of prior chemotherapy is allowed.
• Evidence of progressive disease defined as 1 or more Prostate Cancer Working Group 3 (PCWG3) criteria.
• The patient must have recovered from toxicities related to any prior treatments.
• Castrate at screening.
• Patients receiving bisphosphonates or other approved bone-targeting therapy must be on a stable dose for at least 4 weeks prior to the start of study drug.
• Demonstrate adequate organ function.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.

• Patients are eligible to enroll in this cohort if they meet the clinical criteria for receiving AAP as standard of care treatment as per label (i.e., high-risk mHSPC or mCRPC).

Part B/Cohort 2 (Window of Opportunity with clinical endpoints followed by combination with Apalutamide)

• Male 18 years of age or older.
• Histologically, pathologically, or cytologically confirmed prostate cancer without small cell features.
• Evidence of castration-resistant prostate cancer (CRPC).
• Patients who received a first generation anti-androgen as part of an initial combined androgen blockade therapy or as second-line hormonal therapy must show continuing disease (PSA) progression off the anti-androgen for at least 4 weeks prior to enrollment.
• At least 4 weeks must have elapsed from the use of 5-α reductase inhibitors, estrogens, and any other anti-cancer therapy prior to enrollment.
• At least 4 weeks must have elapsed from major surgery or radiation therapy prior to enrollment.
• The patient must have recovered from toxicities related to any prior treatments.
• Castrate at screening.
• Demonstrate adequate organ function.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.

Exclusion Criteria

• Biologic anti-cancer therapy or a cytotoxic chemotherapy within 4 weeks prior to the start of study drug.
• Use of hormonal agents with anti-tumor activity against prostate cancer within 4 weeks prior to the start of study drug.
• Any lutamides or abiraterone within 14 days or 5 half-lives, whichever is longer prior to start of study drug.
• Use of radium-223 dichloride or other radioligand/radiopharmaceutical within 28 days prior to the start of study drug.
• Received limited-field palliative bone radiotherapy >5 fractions and/or any radiotherapy within 2 weeks prior to the start of study drug.
• Received a blood transfusion within 28 days of screening.
• Received prior chemotherapy (for Part 1b Cohort A only).
• Known intra-cerebral disease or brain metastasis unless adequately treated and stable for the last 4 weeks before enrollment.
• Spinal cord compression.
• Diagnosis of another invasive malignancy within the previous 3 years other than curatively treated non-melanomatous skin cancer or superficial urothelial carcinoma.
• Gastrointestinal disorder affecting absorption.
• Significant cardiovascular disease.
• Concurrent disease or any clinically significant abnormality.
• Use of strong inducers of CYP3A within 14 days of the first dose of study drug.

• Any prior treatment with chemotherapy.

• Use of concomitant CYP2D6 substrates with narrow therapeutic index.
• Known allergies, hypersensitivity, or intolerance to the excipients of AA (refer to AA Investigator's Brochure [IB] or package inserts as appropriate).

Part B Cohort 2 (Window of Opportunity with clinical endpoints followed by combination with Apalutamide)

• Presence of distant metastases, including visceral, nodal and bones involvement. Exception: pelvic lymph nodes < 2 cm in short axis (N1) located below the iliac bifurcation are allowed.
• Symptomatic loco-regional disease requiring medical intervention, such as moderate or severe urinary obstruction or hydronephrosis due to primary tumor.
• Prior treatment with second generation anti-androgens.
• Prior treatment with CYP17 inhibitors.
• Prior treatment with radiopharmaceutical agents, immunotherapy, or any other investigational agent for nmCRPC.
• Prior chemotherapy.
• History or evidence of: prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) within 3 years prior to enrollment; severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events; uncontrolled hypertension.
• Gastrointestinal disorder affecting absorption.
• Use of strong inducers of CYP3A within 14 days of the first dose of study drug.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

ESSA Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hematology Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Washington University School of Medicine in St. Louis

St Louis, Missouri, United States

Comprehensive Cancer Center of NV Las Vegas

Las Vegas, Nevada, United States

Great Lakes Cancer Center

Buffalo, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

BC Cancer

Vancouver, British Columbia, Canada

Centre hospitalier de l'Université de Montréal

Montreal, Quebec, Canada

Countries

United States; Canada

Other Identifiers

EPI-7386-CS-001

Identifier Type: -

Identifier Source: org_study_id