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At end of Phase 1 excessive high pill burden (18 capsules/day)
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EPI-506 | Experimental | Part I: Ascending doses of EPI-506 administered orally to define the maximum tolerated dose. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Assessed by plasma area under the plasma concentration-time curve (AUC) |
| Measure | Description | Time Frame |
|---|---|---|
| Exploratory Objective: Biomarkers | Circulating tumor cells (CTCs) with emphasis on androgen receptor splice variants (AR-V7) | 12-24 months |
| Exploratory Objective: Pain assessments | Assessed by Brief Pain Inventory-Short Form (BPI-SF) instrument |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Scottsdale Healthcare Hospitals DBA HonorHealth | Scottsdale | Arizona | 85258 | United States | ||
| University of Michigan Health System |
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| 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 | Assessed by maximum concentration (Cmax) | 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 | Assessed by observed pre-dose plasma concentration during multiple dosing (Ctrough) | 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 | Assessed by time to reach Cmax (tmax) | 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 | Assessed by apparent terminal elimination half-life (t1/2) | 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 | Assessed by apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) | 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 | Assessed by apparent clearance after extravascular administration (CL/F) | 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-002 | Assessed by AUC | 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-002 | Assessed by Cmax | 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-002 | Assessed by Ctrough | 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-002 | Assessed by tmax | 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-002 | Assessed by t1/2 | 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-002 | Assessed by Vz/F | 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-002 | Assessed by CL/F | 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: Food effect on PK | Following a single-dose of EPI-506 on Days 1 and 4 assessed by AUC | 6 days |
| Part I: Food effect on PK | Following a single-dose of EPI-506 on Days 1 and 4 assessed by Cmax | 6 days |
| Part I: Food effect on PK | Following a single-dose of EPI-506 on Days 1 and 4 assessed by Ctrough | 6 days |
| Part I: Food effect on PK | Following a single-dose of EPI-506 on Days 1 and 4 assessed by tmax | 6 days |
| Part I: Food effect on PK | Following a single-dose of EPI-506 on Days 1 and 4 assessed by t1/2 | 6 days |
| Part I: Food effect on PK | Following a single-dose of EPI-506 on Days 1 and 4 assessed by Vz/F | 6 days |
| Part I: Food effect on PK | Following a single-dose of EPI-506 on Days 1 and 4 assessed by CL/F | 6 days |
| Part I: PSA | Evaluated as a Pharmacodynamic (PD) marker of response | 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 | Assessed by AUC | 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: To evaluate the PK of EPI-506 | Assessed by Cmax | 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: To evaluate the PK of EPI-506 | Assessed by Ctrough | 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: To evaluate the PK of EPI-506 | Assessed by tmax | 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: To evaluate the PK of EPI-506 | Assessed by t1/2 | 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: To evaluate the PK of EPI-506 | Assessed by Vz/F | 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: To evaluate the PK of EPI-506 | Assessed by CL/F | 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: To evaluate the PK of EPI-002 | Assessed by AUC | 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: To evaluate the PK of EPI-002 | Assessed by Cmax | 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: To evaluate the PK of EPI-002 | Assessed by Ctrough | 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: To evaluate the PK of EPI-002 | Assessed by tmax | 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: To evaluate the PK of EPI-002 | Assessed by t1/2 | 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: To evaluate the PK of EPI-002 | Assessed by Vz/F | 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: To evaluate the PK of EPI-002 | Assessed by CL/F | 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 | Radiographic progression evaluated per modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1 | 12 weeks |
| Part II: Objective response | Radiographic progression evaluation per mRECIST v1.1 in patients with measurable soft tissue disease at baseline | 12 weeks |
| 12-24 months |
| Ann Arbor |
| Michigan |
| 48109 |
| United States |
| Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States |
| Seattle Cancer Care Alliance | Seattle | Washington | 98109 | United States |
| British Columbia Cancer Agency - Vancouver Centre | Vancouver | British Columbia | V5Z 4E6 | Canada |
| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| D005834 | Genital Neoplasms, Male |
| D005832 | Genital Diseases, Male |
| D011469 | Prostatic Diseases |
| ID | Term |
|---|---|
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| C000624374 | EPI-506 |
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