Genital Diseases, Male, Genital Neoplasms, Male, Prostatic Diseases, Prostatic Neoplasms
Conditions
Keywords
Prostate Cancer, Metastatic castration-resistant prostate cancer
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.
Interventions
DRUGEPI-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.
Sponsors
ESSA Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Assessed by plasma area under the plasma concentration-time curve (AUC) |
| 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. | Assessed by AUC |
| Part I: Food effect on PK | 6 days | Following a single-dose of EPI-506 on Days 1 and 4 assessed by AUC |
| 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. | Assessed by AUC |
| 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. | Assessed by AUC |
| Part II: Time to PSA progression | 12 months | — |
| Part II: Radiographic progression | 12 weeks | Radiographic progression evaluated per modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1 |
| Part I: PSA | Baseline to Week 12 | Evaluated as a Pharmacodynamic (PD) marker of response |
| Part II: Objective response | 12 weeks | Radiographic progression evaluation per mRECIST v1.1 in patients with measurable soft tissue disease at baseline |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Objective: Biomarkers | 12-24 months | Circulating tumor cells (CTCs) with emphasis on androgen receptor splice variants (AR-V7) |
| Exploratory Objective: Pain assessments | 12-24 months | Assessed by Brief Pain Inventory-Short Form (BPI-SF) instrument |
Countries
Canada, United States
Outcome results
None listed