Safety and Anti-Tumor Study of Oral EPI-506 for Patients With Metastatic Castration-Resistant Prostate Cancer

Phase 1

Terminated

• Conditions: Prostatic Neoplasms; Genital Diseases, Male; Prostatic Diseases; Genital Neoplasms, Male
• Interventions: Drug: EPI-506

• Registration Number: NCT02606123
• Lead Sponsor: ESSA Pharmaceuticals

Brief Summary

The study will consist of 2 parts: Part I (Dose Escalation) and Part II (Dose Expansion). In Part I, patients will participate in single, multiple, and long-term dosing periods using EPI-506 to determine safety, pharmacokinetics, the maximum tolerated dose, and preliminary indications of anti-tumor activity. Part I is an open-label, adaptive 3 + 3 design, dose-escalation study. Approximately six dose levels of EPI-506 will be studied, beginning at 80 mg/day. Enrolled patients may be allowed to escalate to a subsequent dose cohort after their initial twelve weeks. Additional patients may be enrolled at any safe dose level prior to or concurrent with enrolling patients in Part II.

In Part II, 3 patient populations; post-abiraterone metastatic castration-resistant prostate cancer (mCRPC) but enzalutamide-naïve, post-enzalutamide mCRPC but abiraterone-naïve, and post-abiraterone and enzalutamide mCRPC will be studied at the recommended Phase 2 dose (RP2D) determined in Part I over 12 weeks of daily dosing. Approximately 120 patients (40 in each cohort) will be enrolled.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-10
• Study First Submitted: 2015-10-22
• Study First Submitted QC: 2015-11-13
• Study First Posted: 2015-11-17
• Primary Completion: 2017-12
• Study Completion: 2017-12
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-27
• Last Update Posted: 2018-03-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 28

Inclusion Criteria

• Adenocarcinoma of the Prostate
• Metastatic Disease with at least one lesion on bone scan and/or soft tissue on CT/MRI
• Demonstrated progression on abiraterone and/or enzalutamide
• Demonstrated PSA progression within 12 weeks of study participation
• Castrate testosterone levels at screening with continued Luteinizing hormone-releasing hormone (LHRH) therapy
• Eastern Cooperative Oncology Group (ECOG) score between 0-1
• Asymptomatic or mildly symptomatic

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Exclusion Criteria

• Candidates for cytotoxic chemotherapy
• Received more than one line of chemotherapy
• Received more than one treatment course of enzalutamide or abiraterone
• Inadequate washout of prohibited hormonally active agents or other prior treatments for prostate cancer (PCa)
• Known intra-cerebral disease or brain mets
• Spinal cord compression within 6 months
• Prior treatment with investigative androgen receptor (AR) agents

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
EPI-506	EPI-506	Part I: Ascending doses of EPI-506 administered orally to define the maximum tolerated dose.

Primary Outcome Measures

Name	Time	Method
Part I: Safety and tolerability assessed by vital signs, laboratory measurements, and frequency and severity of treatment-related adverse events	12 weeks
Part II: Prostate-specific antigen (PSA) response rate	12 weeks

Secondary Outcome Measures

Name	Time	Method
Part I: Food effect on PK	6 days	Following a single-dose of EPI-506 on Days 1 and 4 assessed by CL/F
Part I: Pharmacokinetics (PK) profile of EPI-002	Pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, 24h, and 48h after dose; Day 8 at pre-dose, and at 15min, 30min 1h, 2h, 4h, 6h, 8h, 12h, 24h after dose.	Assessed by CL/F
Part I: PSA	Baseline to Week 12	Evaluated as a Pharmacodynamic (PD) marker of response
Part II: Safety and tolerability assessed by vital signs, laboratory measurements, and frequency and severity of treatment-related adverse events	12 months
Part II: To evaluate the PK of EPI-506	Day 8 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, and 24h after dose; Week 12 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, and 8h after dose.	Assessed by CL/F
Part II: Time to PSA progression	12 months
Part II: Radiographic progression	12 weeks	Radiographic progression evaluated per modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1
Part I: Pharmacokinetics (PK) profile of EPI-506	Pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, 24h, and 48h after dose; Day 8 at pre-dose, and at 15min, 30min 1h, 2h, 4h, 6h, 8h, 12h, 24h after dose.	Assessed by apparent clearance after extravascular administration (CL/F)
Part I: Define the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D)	9 months
Part II: To evaluate the PK of EPI-002	Day 8 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, and 24h after dose; Week 12 at pre-dose, and at 15min, 30min, 1h, 2h, 4h, 6h, and 8h after dose.	Assessed by CL/F
Part II: Objective response	12 weeks	Radiographic progression evaluation per mRECIST v1.1 in patients with measurable soft tissue disease at baseline

Trial Locations

Locations (5)

Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

British Columbia Cancer Agency - Vancouver Centre; 🇨🇦 Vancouver, British Columbia, Canada

Scottsdale Healthcare Hospitals DBA HonorHealth; 🇺🇸 Scottsdale, Arizona, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

University of Michigan Health System; 🇺🇸 Ann Arbor, Michigan, United States