Phase II Study: Transcatheter Arterial Chemoembolization Therapy In Combination With Sorafenib (TACTICS)
试验速览
- 阶段
- 2 期
- 入组人数
- 228
- 试验地点
- 1
- 主要终点
- Overall Survival
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of the combination therapy with Transcatheter Arterial Chemoembolization (TACE) and sorafenib compared to TACE alone in patients with unresectable hepatocellular carcinoma (HCC) who are not candidates for surgical resection or percutaneous ablation therapy.
详细描述
TACE with sorafenib Group
Sorafenib will be administrated at a dose of 400mg o.d. before the first TACE. After 2days drug rest, TACE will be conducted. Sorafenib will be resumed at a dose of 400mg o.d. from 3 days after TACE(the resumption day can be postponed until 21 days after TACE). When tolerability is confirmed at 1 week after resumption, the dose of sorafenib will be increased to 400mg b.i.d. When tumor increases, TACE will be repeated.
Control group
TACE will be conducted at scheduled day. When tumor increases, TACE will be repeated.
The treatment regimen will be continued until untreatable progression which is defined as follows:
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
- 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
- •Patients aged 20 Years or over
- •Patients who were fully informed of the study beforehand and signed the informed consent to participate in the study.
- •Patients who are expected to live more than 12 weeks.
- •Patients diagnosed with typical HCC by biopsy,cytology, or diagnostic imaging such as dynamic CT(MRI).Typical HCC is defined by AASLD criteria.
- •Patients in whom complete resection of the tumor by hepatectomy or complete tumor necrosis by local tumor necrosis therapy(RFA) cannot be expected to succeed.
- •Patients with tumors which are confirmed to the liver and can be treated by TACE(the maximum diameter equal to or less than 10cm,and the maximum number of nodule equal to or less than 10).
- •Patients with viable and measurable target lesion.
- •patients with no or one history of TACE therapy.
- •patients with an ECOG PS(Performance Status) Score of 0 or
- •patients with Child-Pugh class A.
- •Patients with laboratory values that meet the following criteria:
- •Hemoglobin ≥ 8.5 g/dl
- •Granulocytes ≥ 1500/mm3
- •Platelet count ≥ 50,000 /mm3
- •Total serum bilirubin ≤ 3 mg/dl
- •AST and ALT ≤ 6 times upper limits of normal
- •Serum creatinine ≤ 1.5 times upper limits of normal
排除标准
- •History of malignant tumor, excluding the following cases:
- •Curatively treated early stage cancer with a low risk of recurrence ,such as carcinoma in situ of the cervix, basal cell carcinoma, superficial bladder tumor, and early gastric cancer.
- •Malignant tumor that was curatively treated more than 3 years prior to study entry and has not recurred since then
- •Cardiac disease that meet any of the following criteria:
- •NYHA Class III or higher congestive heart failure
- •History of symptomatic coronary artery disease or myocardial infarction within 6 months before enrollment
- •Arrhythmia requiring control by antiarrhythmic drugs such as beta-blockers or digoxin
- •Serious and active infection, except for HBV and HCV
- •History of HIV infection
- •Renal dialysis
- •Diffuse tumor lesion
- •Extrahepatic metastasis
- •Vascular invasion
- •Intracranial tumor
- •Preexisting or history of hepatic encephalopathy
- •Clinically uncontrolled ascites or pleural effusion
- •Clinically severe gastrointestinal bleeding within 4 weeks of the start of treatment
- •Esophageal and/or gastric varices which has high risk of bleeding
- •History of thrombosis and/or embolism within 6 months of the start of treatment
- •History of receiving any of the following therapies:
- •Systemic chemotherapy for advanced HCC(including sorafenib therapy)
- •Local therapy, such as radiofrequency ablation, TACE, or hepatic arterial infusion within 3 months of the start of treatment
- •Current treatment with CYP3A4 inducing agents
- •Invasive surgery within 4 weeks of the start of treatment
- •History of allogenic transplantation
- •History of bone marrow transplant or haemopoietic stem cell transplant within 4 weeks of the start of this study
- •Unable to take oral medications
- •Gastrointestinal problems that may affect absorption or pharmacokinetics of the study drugs
- •Use of drugs that may affect absorption or pharmacokinetics of the study drugs
- •Concurrent disease or disability that may affect evaluation of the effects of the study drugs
- •Enrollment in another study within 4 weeks of study entry
- •Female patients who are pregnant, lactating, possibly pregnant, or planning to become pregnant
- •Risk of allergic reactions to the study drugs
- •Drug abuse or other physical, psychological , or social problems that may interfere with the participation in the study or evaluation of study results
- •Any condition that could jeopardize the safety of the patient or their compliance in the study
研究组 & 干预措施
TACE with sorafenib
TACE(on demand) with sorafenib till untreatable progression
干预措施: TACE with sorafenib (Drug)
TACE alone
TACE(on demand) till unreatable progression
干预措施: TACE alone (Procedure)
结局指标
主要结局
Overall Survival
时间窗: every 8 week
The overall survival is defined as time from randomization to death due to any cause, and will be evaluated every 8 weeks in the protocol treatment, and every one year in the follow-up period,respectively.
Progression Free Survival
时间窗: every 8 week
Patients will be evaluated for these endpoints every 8 weeks
次要结局
- Time To Untreatable Progression(TTUP)(every 8 week till untreatable progression, assessed up to 100 months)
- Time to intrahepatic tumor progression(every 8 week till intrahepatic tumor progression, assessed up to 100 months)
- Objective Response Rate(4week after TACE)
- Safety(every 4 weeks)
- Tumor markers(every 4 weeks)
- Time to vascular invasion(every 8 week till vascular invasion, assessed up to 100 months)
- Time to Extrahepatic spread(every 8 week till extrahepatic spread, assessed up to 100 months)
- Time To Progression(every 8 weeks)
- Time to Child-Pugh C(every 8 week till liver deterioration to Child-Pugh C, assessed up to 100 months)
研究者
Masatoshi Kudo
Professor, Kindai University Faculty of Medicine, Department of Gastroenterology and Hepatology
Kindai University