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
Overview
- Phase
- Phase 1
- Intervention
- EPI-506
- Conditions
- Prostatic Neoplasms
- Sponsor
- ESSA Pharmaceuticals
- Enrollment
- 28
- Locations
- 5
- Primary Endpoint
- Part I: Safety and tolerability assessed by vital signs, laboratory measurements, and frequency and severity of treatment-related adverse events
- Status
- Terminated
- Last Updated
- 8 years ago
Overview
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.
Investigators
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
Arms & Interventions
EPI-506
Part I: Ascending doses of EPI-506 administered orally to define the maximum tolerated dose.
Intervention: EPI-506
Outcomes
Primary Outcomes
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 Outcomes
- 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.)
- Part I: PSA(Baseline to Week 12)
- 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.)
- Part II: Time to PSA progression(12 months)
- Part II: Radiographic progression(12 weeks)
- 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: 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.)
- Part II: Objective response(12 weeks)
- Part I: Food effect on PK(6 days)