A Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of TR128 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 3
- 主要终点
- Adverse Events and Serious Adverse Events
研究概览
简要总结
This is a open-label, 3+3 design, dose escalation and expansion, phase I study, to evaluate the safety and tolerability, and to determine the Recommended Phase II Dose (RP2D) of TR128 when administered qd in patients with advanced solid tumors. Up to 5 cohorts of 3-6 patients each will be treated in dose escalation phase of the study. One cycle is 28 days. Dose expansion phase to further evaluate the safety, tolerability and preliminary anti-tumor activity of TR128 at the RP2D.
详细描述
This phase I study of TR128 will investigate the tolerability, safety, pharmacokinetics (PK) and preliminary efficacy of TR128, and will define the maximum tolerated dose (MTD) of TR128 using 3+3 design. A dose expansion phase will identify the recommended phase 2 dose. In this clinical study, TR128 is given orally daily. A treatment cycle is defined as 28 days. Patients will receive study treatment until criteria for study termination are met. A safety follow-up visit will be conducted 28 days after the last dose of study treatment. Patients who discontinue study treatment for reasons other disease progression will have post-treatment follow-up for disease assessment until start of new anticancer treatment, patient withdraws consent, is lost to follow-up, death, or until the sponsor stops the study, whichever comes first.
Adverse events (AEs) will be assessed using the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0.
Tumor response will be assessed by computed tomography (CT) and /or magnetic resonance imaging (MRI) scan using RECIST1.1 criteria, assessed by the investigator.
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
- All
- 接受健康志愿者
- 否
入选标准
- •fully understand the procedures of the clinical study and participate voluntarily with signed and dated written informed consent form, comply with the requirements of the study protocol.
- •males and/or females at least 18 years old when signing the informed consent form.
- •histologically or cytologically confirmed patients with advanced malignant solid tumors, eligible patients must have failed standard treatment, no standard treatment, or not suitable for standard treatment at this stage as determined by the investigator.
- •measurable disease with at least one lesion amenable to response assessment per RECIST 1.
- •eastern cooperative oncology group performance status (ECOG) ≤1 at screening.
- •life expectancy of at least 3 months.
- •acceptable organ function: Absolute neutrophil count(ANC)≥1.5×109/L; Platelet count(PLT)≥90×109/L; Hemoglobin(Hb)≥90 g/L; International Normalized Ratio (INR) or Prothrombin Time (PT)≤1.5×Upper limit of normal value (ULN), Activated Partial Thromboplastin Time (APTT)≤1.5×ULN ; Total bilirubin(TBIL)≤1.5×Upper limit of normal value(ULN) (≤3× ULN if there is liver involvement); Alanine aminotransferase(ALT)≤2.5×ULN and aspartate aminotransferase(AST)≤2.5×ULN (≤ 5 × ULN if there is liver involvement); Creatinine (Cr) ≤1.5×ULN or Creatinine Clearance (CCr) ≥50 ml/min (calculated by Cockcroft-Gault formula).
- •fertile male and female must agree to use medically approved contraceptives during the study and within 6 months after the last dose of the study.
排除标准
- •medical history and surgical history excluded according to the protocol.
- •any previous medical treatment history exclude from the protocol.
- •abnormal laboratory results exclude from the protocol.
- •pregnant and lactating women (currently breast-feeding or less than six months after delivery although not breast-feeding).
- •unsuitable for the study by the investigator's judgment.
研究组 & 干预措施
TR128
干预措施: TR128 (Drug)
结局指标
主要结局
Adverse Events and Serious Adverse Events
时间窗: from the first dose to within 30 days after the last dose
Frequency, duration, and severity of Adverse Events and Serious Adverse Events evaluated by NCI CTCAE v5.0
Maximum tolerated dose
时间窗: Throughout the study for approximately 2 years
Evaluated by safety review committee
Recommended phase II dose
时间窗: Throughout the study for approximately 2 years
Evaluated by safety review committee
Dose limited toxicities
时间窗: within 28 days after the first dose
Incidence of dose limited toxicities
次要结局
- Vz/F(within 31 days after the first dose)
- Cmax(within 31 days after the first dose)
- ORR(throughout the study for approximately 2 years)
- PFS(throughout the study for approximately 2 years)
- CL/F(within 31 days after the first dose)
- AUClast(within 31 days after the first dose)
- AUCinf(within 31 days after the first dose)
- Tmax(within 31 days after the first dose)
- DOR(throughout the study for approximately 2 years)
- Terminal half-life (T1/2)(within 31 days after the first dose)
- DCR(throughout the study for approximately 2 years)