A Single-arm, Open-Label, Dose Escalation , Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of TR64 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
- 19
- 试验地点
- 2
- 主要终点
- Adverse Events and Serious Adverse Events
研究概览
简要总结
This is a open-label, dose escalation, accelerated titration combined 3+3 design, phase I study, to evaluate the safety and tolerability, and to determine the RP2D of TR64 when administered qd in patients with advanced solid tumors. Up to 6 cohorts of 1-6 or 3-6 patients each will be treated in the study.
详细描述
Patients will receive study treatment until criteria for study termination are met. A Safety Follow-up Visit will be conducted 28 days (±7 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 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 RECIST 1.1 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 75 Years（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) ≤2 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; Total bilirubin(TBIL)≤1.5×Upper limit of normal value(ULN); Alanine aminotransferase(ALT)≤2.5×ULN; Aspartate aminotransferase(AST)≤2.5×ULN; Creatinine clearance ≥50ml/min.
- •Fertile male and female must agree to use medically approved contraceptives during the study and within 90 days after the last dose of the study.
排除标准
- •Known or suspected allergies to any of the investigational drug composition.
- •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).
- •Subjects may not be able to complete the study duo to poor compliance or other reasons, or unsuitable for the study by the investigator's judgment.
研究组 & 干预措施
TR64
Daily doses by oral administration on each day of each 28 day cycle. Starting dose is 25mg, with escalation to 400mg, and subsequent dose escalation using a modified Fibonacci algorithm.
干预措施: TR64 (Drug)
结局指标
主要结局
Adverse Events and Serious Adverse Events
时间窗: From the first dose to within 28 days after the last dose
Frequency, duration and severity of Adverse Events and Serious Adverse Events evaluated by NCI CTCAE v5.0
Dose limited toxicities
时间窗: within 28 days after the first dose
Incidence of dose limited toxicities
Maximum tolerated dose
时间窗: Throughout the study for approximately 2 years
Evaluated by safety review committee
Recommended phaseII dose
时间窗: Throughout the study for approximately 2 years
Evaluated by safety review committee
次要结局
- AUClast(within 35 days after the first dose)
- AUCinf(within 35 days after the first dose)
- Cmax(within 35 days after the first dose)
- Tmax(within 35 days after the first dose)
- CL/F(within 35 days after the first dose)
- Vz/F(within 35 days after the first dose)
- Terminal half-life (T1/2)(within 35 days after the first dose)