A Phase 1 Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of ACE-232 in Patients With Metastatic Castration-Resistant Prostate Cancer (CRPC)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 88
- 试验地点
- 16
- 主要终点
- Number of patients experiencing adverse events (AEs)/serious adverse events (SAEs)
研究概览
简要总结
This is an open label, phase I, multi-center study aiming to assess the safety and tolerability in patients with metastatic castration resistant prostate cancer (mCRPC).
详细描述
The study consists of two parts, Phase 1A dose escalation and Phase 1B dose optimization. Phase 1A aims to assess the safety, tolerability, pharmacokinetic (PK) profile, and changes in pharmacodynamic (PD) markers in patients treated with ACE-232, and to determine the maximum tolerated dose (MTD), if applicable. In Phase 1B, patients with AR gene alterations will be treated at two different dose levels to establish the recommended Phase 2 dose (RP2D).
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
- •Provide written informed consent
- •Metastatic Castration-resistant Prostate Cancer with ongoing androgen - deprivation therapy (ADT) or have bilateral orchiectomy
- •Difficult to treat or intolerant to standard treatment (post at least 1 line of NHA and taxane-based chemo in mHSPC or mCRPC), suitable for investigational treatment;
- •Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Has a life expectancy of at least 6 months
- •Adequate organ function and bone marrow function
排除标准
- •Receiving any anti-cancer drugs or other treatment, major surgery, extensive radiation therapy, or local radiation therapy within protocol-defined wash-out period;
- •Concomitant use of medications or herbal supplements known to be moderate to strong CYP3A4 inhibitors/inducers, or P-gp inhibitors, known to prolong the QT interval.
- •Any previous treatment-related toxicities have not recovered.
- •Spinal cord compression or known brain metastases or leptomeningeal carcinomatosis.
- •Severe cardiovascular disorders.
- •Known gastrointestinal (GI) disorder or GI procedure
- •History of gastric and duodenal perforation.
- •History of pituitary dysfunction.
- •Poorly controlled diabetes mellitus.
- •Active or uncontrolled autoimmune disease
- •Active infections, or a known history of HIV infection, or a known active hepatitis B or C, or a known active tuberculosis.
- •Other malignancies requiring treatment within 3 years prior to the first dose of study drug
- •Known allergy or hypersensitivity to any of the excipients of ACE-
- •Has other medical conditions that at the discretion of the investigator interfere with safety or efficacy evaluation, or treatment compliance.
研究组 & 干预措施
ACE-232
Administered once daily (QD) continuously at the assigned dose level in accordance with the standard 3+3 dose-escalation scheme
干预措施: ACE-232 tablets (Drug)
结局指标
主要结局
Number of patients experiencing adverse events (AEs)/serious adverse events (SAEs)
时间窗: From time of information consent to 30 days post last dose, up to approximately 37 months
Number of patients with incidence of adverse events and with serious adverse events including changes from baseline in laboratory parameters, vital signs, ECGs, and physical examination, etc.
Recommended Phase 2 dose (RP2D) and/or maximum tolerated dose (MTD)
时间窗: Up to approximately 37 months
RP2D will be finally determined by the SMC and sponsor based on all data from the dose escalation module and backfill module, as well as the exposure-response relationship evaluated (if available). MTD is defined as the maximum dose level at which ≤1 patient have DLTs during the DLT observation period, and it should be determined with 6 evaluable patients.
Number of patients experiencing dose limiting toxicity (DLT), as defined in the protocol
时间窗: From the first dose of ACE-232 on Cycle 1 Day 1 up to and including the planned end of Cycle 1 (at the end of 28 days)
A DLT is defined as any toxicity events related to ACE-232 that occur from the first dose of study treatment until the planned end date of Cycle 1 (DLT assessment period), meeting the criteria specified in protocol.
次要结局
- Pharmacokinetics characterization by using Maximum concentration (Cmax)(Up to approximately 37 months)
- Prostate Specific Antigen (PSA) response(Up to approximately 37 months)
- Pharmacokinetics characterization by using Area under the plasma concentration versus time curve (AUC)(Up to approximately 37 months)
- Objective Response Rate (ORR)(Up to approximately 37 months)
- Duration of Response (DoR)(Up to approximately 37 months)
- Overall Survival (OS)(Up to approximately 37 months)
- Radiographic Progression Free Survival (rPFS)(Up to approximately 37 months)
- Blood concentration of steroid hormone(Up to approximately 37 months)