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

NCT02606123 | Terminated Phase 1

• 1 other identifier: EPI-506-CS-0001
• Study Type: interventional
• Target: 28
• Locations: 2 countries
• Sites: 5

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.

Conditions

Prostatic Neoplasms; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases

Keywords

Prostate Cancer; Metastatic castration-resistant prostate cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (41)

• Part I: Define the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D)

  9 months

• 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.

• 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.

• 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.

• 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.

Other Outcomes (2)

• Exploratory Objective: Biomarkers

  12-24 months

• Exploratory Objective: Pain assessments

  12-24 months

Study Arms (1)

EPI-506

EXPERIMENTAL

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

Drug: EPI-506

Interventions

EPI-506 DRUG

Patients will receive EPI-506 as an oral softgel capsule. Part 1: Approximately six dose levels of EPI-506 will be studied, beginning at 80 mg/day. During the Single-Dose Period, patients will first receive a dose of EPI-506 in the fasted state followed by 2 days of washout, and then patients will receive a second dose of EPI-506 in the fed state followed by 2 days of washout. Patients will then enter the Multiple Dosing and Long-term Dosing Period where they will receive once or twice daily dosing in a fed or fasted state until they meet discontinuation criteria. Part 2: The dose in Part 2 will be determined in Part 1 of the study. Patients will receive the Part 2 dose daily until they meet discontinuation criteria.

EPI-506

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ESSA Pharmaceuticals: lead

Study Sites (5)

Scottsdale Healthcare Hospitals DBA HonorHealth

Scottsdale, Arizona, 85258, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

British Columbia Cancer Agency - Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases

Interventions

EPI-506

Condition Hierarchy (Ancestors)

Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Frank Perabo, MD, PhD

  ESSA Pharmaceuticals Corp.

  STUDY DIRECTOR

• Robert B. Montgomery, MD

  Seattle Cancer Care Alliance

  PRINCIPAL INVESTIGATOR

• Kim N. Chi, MD

  British Columbia Cancer Agency - Vancouver Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2015
• First Posted: November 17, 2015
• Study Start: October 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: March 1, 2018

Record last verified: 2018-02

Locations

US (4); CA (1)