A Phase I Open Label/Phase II Randomized, Double-Blind, Multicenter Trial Investigating the Combination of Everolimus and TransArterial ChemoEmbolization (TACE) With Doxorubicin in Patients With Hepatocellular Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 27
- 试验地点
- 8
- 主要终点
- Dose-limiting toxicity (Phase I)
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Chemoembolization kills tumor cells by carrying drugs directly into the tumor and blocking the blood flow to the tumor. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether transarterial chemoembolization with doxorubicin is more effective when given alone or when given together with everolimus in treating patients with liver cancer.
PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of everolimus when given together with transarterial chemoembolization with doxorubicin and to see how well it works compared with giving transarterial chemoembolization with doxorubicin alone in treating patients with liver cancer.
详细描述
OBJECTIVES:
- Determine the recommended dose of everolimus in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization with doxorubicin-eluting beads (TACE). (Phase I)
- Determine the efficacy and tolerability of everolimus in patients with HCC treated with TACE as compared to TACE alone. (Phase II)
OUTLINE: This is a multicenter, dose-escalation phase I study followed by a randomized phase II study.
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Phase I: Patients receive oral everolimus once daily in the absence of disease progression or unacceptable toxicity. Beginning 7 days after the start of everolimus patients undergo transarterial chemoembolization (TACE) comprising doxorubicin-eluting beads into the hepatic artery followed in 4 weeks by an MRI. If viable tumor is found patients undergo another TACE treatment continuing every 4 weeks for up to 5 treatments.
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Phase II: Patients are stratified according to center, age (≤ 60 vs > 60 years), and number of lesions (≤ 3 vs > 3). Patients are randomized to 1 of 2 treatment arms.
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Arm I: Patients receive oral placebo once daily for up to 12 months and undergo TACE comprising doxorubicin-eluting beads as in phase I at the maximum tolerated dose (MTD).
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Arm II: Patients receive oral everolimus once daily for up to 12 months and undergo TACE comprising doxorubicin-eluting beads as in phase I at the MTD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive oral placebo once daily for up to 12 months and undergo TACE comprising doxorubicin-eluting beads as in phase I at the MTD.
干预措施: doxorubicin-eluting beads (Drug)
Arm I
Patients receive oral placebo once daily for up to 12 months and undergo TACE comprising doxorubicin-eluting beads as in phase I at the MTD.
干预措施: placebo (Other)
Arm II
Patients receive oral everolimus once daily for up to 12 months and undergo TACE comprising doxorubicin-eluting beads as in phase I at the MTD.
干预措施: doxorubicin-eluting beads (Drug)
Arm II
Patients receive oral everolimus once daily for up to 12 months and undergo TACE comprising doxorubicin-eluting beads as in phase I at the MTD.
干预措施: everolimus (Drug)
结局指标
主要结局
Dose-limiting toxicity (Phase I)
时间窗: after 6 weeks from registration
Dose limiting toxicity (DLT) (observed within the first TACE period)
Time to progression (Phase II)
时间窗: 12 weeks after randomisation
次要结局
- Time to progression (Phase I)(12 weeks after registration)
- Progression-free survival (Phase II)(Time from randomization until event occurs (see description):)
- Progression-free survival at 12 months (Phase II)(within 12 months after randomisation)
- Tumor response according to adapted RECIST criteria (Phase II)(during treatment)
- Overall survival (Phase II)(Time from randomisation until death from any cause)
- Response duration (Phase II)(See description)
- Time to treatment failure (Phase II)(See description)