Clinical trial NCT02606123: Safety and Anti-Tumor Study of Oral EPI-506 for Patients With Metastatic Castration-Resistant Prostate Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Prostatic Neoplasms
Genital Neoplasms, Male
Genital Diseases, Male
Prostatic Diseases
Keywords: Prostate Cancer
Metastatic castration-resistant prostate cancer
Lead sponsor: ESSA Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2015-11-17
Enrollment: 28
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Part I: Safety and tolerability assessed by vital signs, laboratory measurements, and frequency and severity of treatment-related adverse events
timeFrame: 12 weeks
measure: Part II: Prostate-specific antigen (PSA) response rate
timeFrame: 12 weeks
Secondary outcomes:
measure: Part I: Define the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D)
timeFrame: 9 months
measure: Part I: Pharmacokinetics (PK) profile of EPI-506
timeFrame: 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.
measure: Part I: Pharmacokinetics (PK) profile of EPI-506
timeFrame: 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.
measure: Part I: Pharmacokinetics (PK) profile of EPI-506
timeFrame: 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.
measure: Part I: Pharmacokinetics (PK) profile of EPI-506
timeFrame: 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.
measure: Part I: Pharmacokinetics (PK) profile of EPI-506
timeFrame: 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.
measure: Part I: Pharmacokinetics (PK) profile of EPI-506
timeFrame: 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.
measure: Part I: Pharmacokinetics (PK) profile of EPI-506
timeFrame: 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.
measure: Part I: Pharmacokinetics (PK) profile of EPI-002
timeFrame: 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.
measure: Part I: Pharmacokinetics (PK) profile of EPI-002
timeFrame: 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.
measure: Part I: Pharmacokinetics (PK) profile of EPI-002
timeFrame: 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.
measure: Part I: Pharmacokinetics (PK) profile of EPI-002
timeFrame: 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.
measure: Part I: Pharmacokinetics (PK) profile of EPI-002
timeFrame: 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.
measure: Part I: Pharmacokinetics (PK) profile of EPI-002
timeFrame: 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.
measure: Part I: Pharmacokinetics (PK) profile of EPI-002
timeFrame: 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.
measure: Part I: Food effect on PK
timeFrame: 6 days
measure: Part I: Food effect on PK
timeFrame: 6 days
measure: Part I: Food effect on PK
timeFrame: 6 days
measure: Part I: Food effect on PK
timeFrame: 6 days
measure: Part I: Food effect on PK
timeFrame: 6 days
measure: Part I: Food effect on PK
timeFrame: 6 days
measure: Part I: Food effect on PK
timeFrame: 6 days
measure: Part I: PSA
timeFrame: Baseline to Week 12
measure: Part II: Safety and tolerability assessed by vital signs, laboratory measurements, and frequency and severity of treatment-related adverse events
timeFrame: 12 months
measure: Part II: To evaluate the PK of EPI-506
timeFrame: 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.
measure: Part II: To evaluate the PK of EPI-506
timeFrame: 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.
measure: Part II: To evaluate the PK of EPI-506
timeFrame: 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.
measure: Part II: To evaluate the PK of EPI-506
timeFrame: 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.
measure: Part II: To evaluate the PK of EPI-506
timeFrame: 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.
measure: Part II: To evaluate the PK of EPI-506
timeFrame: 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.
measure: Part II: To evaluate the PK of EPI-506
timeFrame: 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.
measure: Part II: To evaluate the PK of EPI-002
timeFrame: 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.
measure: Part II: To evaluate the PK of EPI-002
timeFrame: 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.
measure: Part II: To evaluate the PK of EPI-002
timeFrame: 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.
measure: Part II: To evaluate the PK of EPI-002
timeFrame: 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.
measure: Part II: To evaluate the PK of EPI-002
timeFrame: 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.
measure: Part II: To evaluate the PK of EPI-002
timeFrame: 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.
measure: Part II: To evaluate the PK of EPI-002
timeFrame: 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.
measure: Part II: Time to PSA progression
timeFrame: 12 months
measure: Part II: Radiographic progression
timeFrame: 12 weeks
measure: Part II: Objective response
timeFrame: 12 weeks
Other outcomes:
measure: Exploratory Objective: Biomarkers
timeFrame: 12-24 months
measure: Exploratory Objective: Pain assessments
timeFrame: 12-24 months
Locations:
city: Scottsdale
country: United States
facility: Scottsdale Healthcare Hospitals DBA HonorHealth
state: Arizona
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency - Vancouver Centre
state: British Columbia
Study officials:
affiliation: ESSA Pharmaceuticals Corp.
name: Frank Perabo, MD, PhD
role: STUDY_DIRECTOR
affiliation: Seattle Cancer Care Alliance
name: Robert B. Montgomery, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: British Columbia Cancer Agency - Vancouver Centre
name: Kim N. Chi, MD
role: PRINCIPAL_INVESTIGATOR
References: