A Phase 1b Study of EPI-7386 in Combination With Abiraterone Acetate Plus Prednisone or Apalutamide in mCRPC (ARES: Androgen Receptor Eradication Study)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 4
- 主要终点
- Number of Participants with Dose-limiting Toxicities (DLT)
研究概览
简要总结
The purpose of this study is to determine safety, including dose limiting toxicities, and the recommended phase 2 dose (RP2D) of EPI-7386 in separate combinations with (a) abiraterone acetate plus prednisone or prednisolone (AAP) and (b) apalutamide (dose-finding) and to determine the antitumor activity of EPI-7386 in separate combinations with (a) AAP and (b) apalutamide (dose-expansion).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed prostate adenocarcinoma
- •Must be able to continue Gonadotropin-releasing hormone agonist (GnRHa) during the study if not surgically castrate
- •Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1, or 2
- •Must be able to swallow oral medicines
- •Contraceptive use by men (and female partners of men enrolled in the study who are of childbearing potential or are pregnant) (birth control) use should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies
- •Willing and able to adhere to the prohibitions and restrictions specified in this protocol
排除标准
- •Known central nervous system (CNS) metastases
- •Non-metastatic castration-resistant prostate cancer (CRPC) (biochemical or locoregional disease only) is excluded from trial participation
- •Evidence of predominant neuroendocrine/small cell carcinoma features in archival or baseline tumor biopsy specimen(s)
- •Symptomatic or impending spinal cord compression, except if participant has received definitive treatment and demonstrates evidence of clinically stable disease
- •Known disorder affecting gastrointestinal absorption
研究组 & 干预措施
Group A: EPI-7386 + Abiraterone Acetate Plus Prednisone (AAP)
Participants with metastatic castration-resistant prostate cancer (mCRPC) will receive EPI-7386 + AAP to determine the recommended phase 2 dose (RP2D) dose of EPI-7386 in combination with AAP in dose finding portion of the study. In dose expansion portion of the study, participants will receive EPI-7386 RP2D in combination with AAP.
干预措施: EPI-7386 (Drug)
Group A: EPI-7386 + Abiraterone Acetate Plus Prednisone (AAP)
Participants with metastatic castration-resistant prostate cancer (mCRPC) will receive EPI-7386 + AAP to determine the recommended phase 2 dose (RP2D) dose of EPI-7386 in combination with AAP in dose finding portion of the study. In dose expansion portion of the study, participants will receive EPI-7386 RP2D in combination with AAP.
干预措施: Abiraterone Acetate (Drug)
Group A: EPI-7386 + Abiraterone Acetate Plus Prednisone (AAP)
Participants with metastatic castration-resistant prostate cancer (mCRPC) will receive EPI-7386 + AAP to determine the recommended phase 2 dose (RP2D) dose of EPI-7386 in combination with AAP in dose finding portion of the study. In dose expansion portion of the study, participants will receive EPI-7386 RP2D in combination with AAP.
干预措施: Prednisone or Prednisolone (Drug)
Group B: EPI-3786 + Apalutamide
Participants with mCRPC will receive EPI-7386 + apalutamide to determine RP2D dose of EPI-7386 in combination with apalutamide in dose finding portion of the study. In dose expansion portion of the study, participants will receive EPI-7386 RP2D in combination with apalutamide.
干预措施: EPI-7386 (Drug)
Group B: EPI-3786 + Apalutamide
Participants with mCRPC will receive EPI-7386 + apalutamide to determine RP2D dose of EPI-7386 in combination with apalutamide in dose finding portion of the study. In dose expansion portion of the study, participants will receive EPI-7386 RP2D in combination with apalutamide.
干预措施: Apalutamide (Drug)
结局指标
主要结局
Number of Participants with Dose-limiting Toxicities (DLT)
时间窗: Up to 28 days of Cycle 1 (each cycle of 28 days)
The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Composite Response Rate
时间窗: At 12 weeks
Composite response rate at 12 weeks, defined as either 90 percent (%) reduction in prostate-specific antigen (PSA) level from baseline (PSA-90), or objective response (confirmed per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1) in participants with measurable disease, or both at 12 weeks.
Number of Participants with Adverse Events (AEs)
时间窗: Up to 3 Years 3 Months
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Number of Participants with AEs by Severity
时间窗: Up to 3 Years 3 Months
Number of participants with AEs by severity will be reported.
次要结局
- Minimum Observed Serum Concentration (Cmin) of EPI-7386 and Abiraterone(Day 1 of each cycle up to 3 cycles (each cycle of 28 days))
- Observed Accumulation Index Based on Cmax (ARCmax) of EPI-7386 and Abiraterone(Day 1 of each cycle up to 3 cycles (each cycle of 28 days))
- Accumulation Ratio for AUCtau (AR AUCtau) of EPI-7386 and Abiraterone(Day 1 of each cycle up to 3 cycles (each cycle of 28 days))
- Maximum Observed Serum Concentration (Cmax) of EPI-7386 and Apalutamide(Day 1 of each cycle up to 3 cycles (each cycle of 28 days))
- Time to Reach Maximum Observed Serum Concentration (Tmax) of EPI-7386 and apalutamide(Day 1 of each cycle up to 3 cycles (each cycle of 28 days))
- Observed Accumulation Index Based on Cmax (ARCmax) of EPI-7386 and Apalutamide(Day 1 of each cycle up to 3 cycles (each cycle of 28 days))
- Area Under the Curve From Time Zero to tau (AUC[0-tau]) of EPI-7386 and Apalutamide(Day 1 of each cycle up to 3 cycles (each cycle of 28 days))
- Maximum Observed Serum Concentration (Cmax) of EPI-7386 and Abiraterone(Day 1 of each cycle up to 3 cycles (each cycle of 28 days))
- Time to Reach Maximum Observed Serum Concentration (Tmax) of EPI-7386 and Abiraterone(Day 1 of each cycle up to 3 cycles (each cycle of 28 days))
- Area Under the Curve From Time Zero to tau (AUC[0-tau]) of EPI-7386 and Abiraterone(Day 1 of each cycle up to 3 cycles (each cycle of 28 days))
- Minimum Observed Serum Concentration (Cmin) of EPI-7386 and Apalutamide(Day 1 of each cycle up to 3 cycles (each cycle of 28 days))
- Accumulation Ratio for AUCtau (AR AUCtau) of EPI-7386 and Apalutamide(Day 1 of each cycle up to 3 cycles (each cycle of 28 days))
- Serum Prostate-Specific Antigen (PSA)(Up to 3 Years 3 Months)