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Clinical Trial 21559

Cancer Type: Genitourinary
Study Type: Treatment
NCT#: NCT05075577

Phase: Phase I/II
Principal Investigator: Zhang, Jingsong

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or 1-800-679-0775 Learn More

Overview

Study 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

Summary

Objective

Phase 1: Single Arm Dose Escalation Primary Objectives: To determine the safety and tolerability, maximum tolerated dose (MTD) and/or recommended Phase 2 combination dose (RP2CD), and dose limiting toxicities (DLTs) of EPI-7386 when administered in combination with a fixed dose of enzalutamide in subjects with metastatic castration-resistant prostate cancer (mCRPC) naïve to second generation anti-androgens. To establish the RP2CD of enzalutamide when used in combination with EPI-7386 in this subject population. Secondary Objectives: To evaluate the pharmacokinetics (PK) of EPI-7386 when dosed alone and in combination with enzalutamide in this subject population. To evaluate the PK of enzalutamide when dosed in combination with EPI-7386 in this subject population. Exploratory Objective: To evaluate preliminary antitumor activity of EPI-7386 in combination with enzalutamide in this subject population. Phase 2: Two Arm Randomized Primary Objectives To evaluate the antitumor activity of EPI7386 in combination with a fixed dose of enzalutamide compared with enzalutamide as a single agent in subjects with mCRPC naïve to second generation anti-androgens. To evaluate the safety of EPI-7386 in combination with a fixed dose enzalutamide compared with enzalutamide as a single agent in this subject population. Secondary Objectives: To evaluate the PK of EPI-7386 when dosed in combination with a fixed dose enzalutamide in this subject population. To evaluate the PK of enzalutamide when dosed in combination with EPI-7386 in this subject population.

Treatments

Therapies

Hormonal Therapy

Medications

EPI-7386 (); Enzalutamide (Xtandi); Not Applicable ()

Inclusion Criteria

Inclusion Criteria:

Males 18 years.of age or more

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/ or MRI or PSMA PET scans.Note: Where available, PSMA PET is an allowed scan modality for documentation of metastatic disease at study entry only. However, baseline bone, CT or MRI scans are still needed to allow for a longitudinal evaluation of response to treatment following PCWG3 criteria and RECIST 1.1. for nodal and visceral disease. The same imaging modality used at baseline (CT or MRI) is to be used throughout the study for a given subject.

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).

Patients 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.

Participant 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.

All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v5.0 Grade 1 or less.

Willing and able to comply with the protocol, including follow-up visits and examinations.

Exclusion Criteria

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, including allergies to sulfonamides

Use of strong inhibitors of CYP2C8 within 14 days prior to start of study drug treatment as this may increase enzalutamide exposure.

Use of strong inducers of CYP3A (e.g., rifampin) within 30 days prior to start of study drug treatment as this may decrease EPI-7386 and enzalutamide exposure.

Use of granulocyte colony stimulating factor within 7 days prior to screening laboratories.

Ongoing participation in another therapeutic trial or use of another investigational agent within 28 days prior to the first dose of EPI-7386.

For Phase 2 subjects, prior participation in Phase 1.

Other exclusions may apply

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