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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02606123
First Posted: November 17, 2015
Last Update Posted: October 4, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
ESSA Pharmaceuticals
  Purpose

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.


Condition Intervention Phase
Prostatic Neoplasms Genital Neoplasms, Male Genital Diseases, Male Prostatic Diseases Drug: EPI-506 Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open-Label Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral EPI-506 in Patients With Metastatic Castration-Resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by ESSA Pharmaceuticals:

Primary Outcome Measures:
  • Part I: Safety and tolerability assessed by vital signs, laboratory measurements, and frequency and severity of treatment-related adverse events [ Time Frame: 12 weeks ]
  • Part II: Prostate-specific antigen (PSA) response rate [ Time Frame: 12 weeks ]

Secondary Outcome Measures:
  • Part I: Define the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) [ Time Frame: 9 months ]
  • Part I: Pharmacokinetics (PK) profile of EPI-506 [ Time Frame: 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 plasma area under the plasma concentration-time curve (AUC)

  • Part I: Pharmacokinetics (PK) profile of EPI-506 [ Time Frame: 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 maximum concentration (Cmax)

  • Part I: Pharmacokinetics (PK) profile of EPI-506 [ Time Frame: 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 observed pre-dose plasma concentration during multiple dosing (Ctrough)

  • Part I: Pharmacokinetics (PK) profile of EPI-506 [ Time Frame: 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 time to reach Cmax (tmax)

  • Part I: Pharmacokinetics (PK) profile of EPI-506 [ Time Frame: 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 terminal elimination half-life (t1/2)

  • Part I: Pharmacokinetics (PK) profile of EPI-506 [ Time Frame: 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 volume of distribution during the terminal phase after extravascular administration (Vz/F)

  • Part I: Pharmacokinetics (PK) profile of EPI-506 [ Time Frame: 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: Pharmacokinetics (PK) profile of EPI-002 [ Time Frame: 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 AUC

  • Part I: Pharmacokinetics (PK) profile of EPI-002 [ Time Frame: 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 Cmax

  • Part I: Pharmacokinetics (PK) profile of EPI-002 [ Time Frame: 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 Ctrough

  • Part I: Pharmacokinetics (PK) profile of EPI-002 [ Time Frame: 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 tmax

  • Part I: Pharmacokinetics (PK) profile of EPI-002 [ Time Frame: 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 t1/2

  • Part I: Pharmacokinetics (PK) profile of EPI-002 [ Time Frame: 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 Vz/F

  • Part I: Pharmacokinetics (PK) profile of EPI-002 [ Time Frame: 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: Food effect on PK [ Time Frame: 6 days ]
    Following a single-dose of EPI-506 on Days 1 and 4 assessed by AUC

  • Part I: Food effect on PK [ Time Frame: 6 days ]
    Following a single-dose of EPI-506 on Days 1 and 4 assessed by Cmax

  • Part I: Food effect on PK [ Time Frame: 6 days ]
    Following a single-dose of EPI-506 on Days 1 and 4 assessed by Ctrough

  • Part I: Food effect on PK [ Time Frame: 6 days ]
    Following a single-dose of EPI-506 on Days 1 and 4 assessed by tmax

  • Part I: Food effect on PK [ Time Frame: 6 days ]
    Following a single-dose of EPI-506 on Days 1 and 4 assessed by t1/2

  • Part I: Food effect on PK [ Time Frame: 6 days ]
    Following a single-dose of EPI-506 on Days 1 and 4 assessed by Vz/F

  • Part I: Food effect on PK [ Time Frame: 6 days ]
    Following a single-dose of EPI-506 on Days 1 and 4 assessed by CL/F

  • Part I: PSA [ Time Frame: 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 [ Time Frame: 12 months ]
  • Part II: To evaluate the PK of EPI-506 [ Time Frame: 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 AUC

  • Part II: To evaluate the PK of EPI-506 [ Time Frame: 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 Cmax

  • Part II: To evaluate the PK of EPI-506 [ Time Frame: 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 Ctrough

  • Part II: To evaluate the PK of EPI-506 [ Time Frame: 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 tmax

  • Part II: To evaluate the PK of EPI-506 [ Time Frame: 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 t1/2

  • Part II: To evaluate the PK of EPI-506 [ Time Frame: 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 Vz/F

  • Part II: To evaluate the PK of EPI-506 [ Time Frame: 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: To evaluate the PK of EPI-002 [ Time Frame: 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 AUC

  • Part II: To evaluate the PK of EPI-002 [ Time Frame: 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 Cmax

  • Part II: To evaluate the PK of EPI-002 [ Time Frame: 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 Ctrough

  • Part II: To evaluate the PK of EPI-002 [ Time Frame: 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 tmax

  • Part II: To evaluate the PK of EPI-002 [ Time Frame: 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 t1/2

  • Part II: To evaluate the PK of EPI-002 [ Time Frame: 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 Vz/F

  • Part II: To evaluate the PK of EPI-002 [ Time Frame: 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 [ Time Frame: 12 months ]
  • Part II: Radiographic progression [ Time Frame: 12 weeks ]
    Radiographic progression evaluated per modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1

  • Part II: Objective response [ Time Frame: 12 weeks ]
    Radiographic progression evaluation per mRECIST v1.1 in patients with measurable soft tissue disease at baseline


Other Outcome Measures:
  • Exploratory Objective: Biomarkers [ Time Frame: 12-24 months ]
    Circulating tumor cells (CTCs) with emphasis on androgen receptor splice variants (AR-V7)

  • Exploratory Objective: Pain assessments [ Time Frame: 12-24 months ]
    Assessed by Brief Pain Inventory-Short Form (BPI-SF) instrument


Estimated Enrollment: 166
Study Start Date: October 2015
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EPI-506
Part I: Ascending doses of EPI-506 administered orally to define the maximum tolerated dose.
Drug: EPI-506

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.


  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02606123


Locations
United States, Arizona
Scottsdale Healthcare Hospitals DBA HonorHealth
Scottsdale, Arizona, United States, 85258
United States, Michigan
University of Michigan Health System
Ann Arbor, Michigan, United States, 48109
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Canada, British Columbia
British Columbia Cancer Agency - Vancouver Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Sponsors and Collaborators
ESSA Pharmaceuticals
Investigators
Study Director: Frank Perabo, MD, PhD ESSA Pharmaceuticals Corp.
Principal Investigator: Robert B. Montgomery, MD Seattle Cancer Care Alliance
Principal Investigator: Kim N. Chi, MD British Columbia Cancer Agency - Vancouver Centre
  More Information

Responsible Party: ESSA Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02606123     History of Changes
Other Study ID Numbers: EPI-506-CS-0001
First Submitted: October 22, 2015
First Posted: November 17, 2015
Last Update Posted: October 4, 2017
Last Verified: October 2017

Keywords provided by ESSA Pharmaceuticals:
Prostate Cancer
Metastatic castration-resistant prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Neoplasms
Prostatic Diseases
Genital Neoplasms, Male
Genital Diseases, Male
Urogenital Neoplasms
Neoplasms by Site