An Open-Label, Single-Arm, Two-Stage, Multi-Centre Phase II Study to Evaluate the Efficacy and Safety of TLC388 as Second-line Treatment in Subjects With Advanced Hepatocellular Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 29
- 试验地点
- 12
- 主要终点
- Disease Control Rate (DCR)
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of TLC388 (Lipotecan) as a second line treatment in subjects with advanced Hepatocellular Carcinoma.
详细描述
A Phase II, open-label, single-arm, two-stage, multicenter study to evaluate the efficacy and safety of Lipotecan® monotherapy in patients with advanced hepatocellular carcinoma (HCC) and had failed sorafenib treatment due to sorafenib intolerance or radiographic progressive disease (PD).
Eligible patients received 40 mg/m2 of Lipotecan®, given as a 30-minute (+3 minutes) intravenous infusion, on Days 1, 8, and 15 of a 28-day cycle for maximum 6 cycles. Inter-cycle and intra-cycle dose delays were allowed within 21 days of the scheduled date to be reduced to 35 mg/m2 and further to 30 mg/m2 if a treatment-related adverse event (TRAE) met the criteria for dose reduction.
Tumor response was assessed every 2 cycles until Cycle 6, or at the early termination according to RECIST Version 1.1 judged by site investigator. The favorable response of CR, PR or SD would be confirmed within 28-35 days. Safety evaluations were conducted on a weekly basis from the day study treatment administered throughout each cycle.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Radiological diagnosis of hepatic tumor(s) by contrast-enhanced study
- •Subjects with advanced HCC who are not eligible for surgical resection or loco-regional therapy.
- •Subjects with sorafenib treatment failure due to sorafenib intolerance or radiographic PD (as per RECIST v1.1). Prior sorafenib use should be ≥ 400 mg/day for at least 14 days.
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
- •Child Pugh Score ≤ 6;
- •A life expectancy of at least 12 weeks or more
排除标准
- •Subjects who have received any systemic target therapy or systemic chemotherapy other than sorafenib for the treatment of HCC.
- •Subjects who have received sorafenib within 2 weeks prior to the initiation of the treatment dose, or have any sorafenib-related toxicities not yet resolved to grade 1 or baseline.
- •Subjects who have undergone liver transplantation surgery.
- •Major surgery within 4 weeks prior to the initiation of the treatment dose (excluding implantation of the intravenous infusion device). Percutaneous liver puncture within 2 weeks prior to the initiation of the treatment dose.
研究组 & 干预措施
Lipotecan
Administer 40mg of Lipotecan at D1, D8, D15 of each cycles.
干预措施: Lipotecan (Drug)
结局指标
主要结局
Disease Control Rate (DCR)
时间窗: 8 weeks from initial treatment
DCR (Disease control rate), the percentage of subjects with a best response rate of complete response (CR), partial response (PR), or stable disease (SD)
次要结局
- Overall Survival (OS)(Up to 2 years from the last treatment of the last subject)
- Vital signs(Baseline, first treatment(C1D1), 1, 2, 4, 5, 6, 8, 9, 10, 12, 13, 14, 16, 17, 18, 20, 21, 22 weeks from the first treatment and/or Early termination (up to 24 weeks))
- Duration of Disease control (DDC)(2 months (Cycle 2), 4 months (Cycle 4) and 6 months (Cycle 6) and/or Early termination (before 6 months))
- Time to Progression (TTP)(2 months (Cycle 2), 4 months (Cycle 4) and 6 months (Cycle 6) and/or Early termination (before 6 months))
- Clinical chemistry(Baseline, first treatment(C1D1), 1, 2, 4, 5, 6, 8, 9, 10, 12, 13, 14, 16, 17, 18, 20, 21, 22 weeks from the first treatment and/or Early termination (up to 24 weeks))
- AEs(From ICF singed to 30 days after EOT)
- Objective response rate (ORR; where ORR= CR rate + PR rate)(8 weeks(Cycle 2), 16 weeks (Cycle 4), 24 weeks (Cycle 6) from initial treatment and/or Early termination (before 24 weeks))
- Progression Free Survival (PFS)(2 months (Cycle 2), 4 months (Cycle 4) and 6 months (Cycle 6) and/or Early termination (before 6 months))
- Change of Tumor markers/Bio-markers(Baseline, the first dose (Cycle 1 Day 1), 2 months(C2D1), 3 months(C3D1), 4 months(C4D1), 5 months(C5D1), 6 months(C6D1) and/or Early termination (before 6 months))
- Resting 12-lead ECGs(Baseline, the first dose (Cycle 1 Day 1), 2 months(C2D1), 3 months(C3D1), 4 months(C4D1), 5 months(C5D1), 6 months(C6D1) and/or Early termination (before 6 months))
- Urinalysis data(The first dose (Cycle 1 Day 1), 2 months(C2D1), 3 months(C3D1), 4 months(C4D1), 5 months(C5D1), 6 months(C6D1) and/or Early termination (before 6 months))
- Hematology(Baseline, first treatment(C1D1), 1, 2, 4, 5, 6, 8, 9, 10, 12, 13, 14, 16, 17, 18, 20, 21, 22 weeks from the first treatment and/or Early termination (up to 24 weeks))
- PK parameters, including AUC, Cmax and Tmax of S,S-TLC388, S,R-TLC388, metabolites TLC-U1, TLC-U2, and topotecan(0, 15, 29, 33, 40, 50 minutes, and 1, 1.5, 2, 4, 8 hour after the start of infusion of the 1st treatment and 1 week (2nd treatment); 0, 29 minutes and 4 hour after the start of infusion of the 3, 5, 6 and 7 weeks (the 3rd, 4th, 5th, 6th treatment))