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
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 28
- 试验地点
- 5
- 主要终点
- Part I: Safety and tolerability assessed by vital signs, laboratory measurements, and frequency and severity of treatment-related adverse events
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
EPI-506
Part I: Ascending doses of EPI-506 administered orally to define the maximum tolerated dose.
干预措施: EPI-506 (Drug)
结局指标
主要结局
Part I: Safety and tolerability assessed by vital signs, laboratory measurements, and frequency and severity of treatment-related adverse events
时间窗: 12 weeks
Part II: Prostate-specific antigen (PSA) response rate
时间窗: 12 weeks
次要结局
- 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)