Sorafenib as Inhibitor of Collateral Tumor Vessel Growth During Transarterial Chemoembolisation (TACE) for Hepatocellular Carcinoma (HCC)- a Pilot Trial to Evaluate Safety and Biological Response
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Time to Progression (Efficacy)
研究概览
简要总结
Hepatocellular carcinoma (HCC) as the third most common cause of cancer-related death has a very poor prognosis. Aim of this open label single arm non randomized pilot trial is the evaluation of the efficacy and safety of sorafenib in combination with TACE in patients with unresectable HCC. Efficacy ad safety will be compared with a historical TACE-only group of a placebo controlled TACE-trial.
详细描述
Hepatocellular carcinoma (HCC) as the third most common cause of cancer-related death has a very poor prognosis.
Aim 1: Efficacy of Sorafenib in combination with TACE TACE is an established therapy for patients with unresectable HCC and has been shown to significantly improve survival in these patients compared to no treatment. Quite often after cutting off the blood supply through the hepatic artery, the tumor induces active angiogenesis to promote collateral blood vessel growth from liver capsule arteries or collaterals from the gastroduodenal artery leading to tumor recovery and proliferation. Inhibition of this neoangiogenetic and proliferation activity after TACE by the multikinase inhibitor Sorafenib, already approved for HCC, could lead to significantly improvement in tumor control and survival in patients with advanced stage HCC.Safety will be compared with a historical TACE-only group of a placebo controlled TACE-trial.
Aim 2: Safety of Sorafenib in combination with TACE:
So far there are no reports about the safety of Sorafenib in combination with TACE. Here we evaluate the safety and tolerability of this combination until 12 weeks after the last TACE.
Aim 3: PPG-Measurement:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Patients with histologically confirmed HCC not suitable for OLT or resection ( > 3 nodules, >5 cm diameter, vascular invasion, clinically significant portal hypertension, other contraindications against OLT)
- •Child-Pugh Stage A or B
- •Liver disease of any etiology
- •Written informed consent (approved by the Institutional Review Board [IRB]/Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures
- •Patient must be able to comply with the protocol
- •Age ≥ 18 years
- •Women of childbearing potential must have a negative serum pregnancy test done 1 week prior to the administration of the Sorafenib.
- •Fertile women and men of childbearing potential ( < 2 years after last menstruation in women) must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile)
- •Haematology:
- •Absolute neutrophil count (ANC) > 1 x 109/L Platelet count > 40 x 109/L Haemoglobin > 9 g/dL (may be transfused to maintain or exceed this level) Prothrombin time ≥ 40%
- •Biochemistry:
- •Total bilirubin < 5 mg/dL Serum creatinine < 3.0 mg/dL
- •Life expectancy of > 3 months
排除标准
- •Extrahepatic tumor spread
- •Complete portal vein thrombosis (common trunk)
- •Child-Pugh-Stage C
- •Prior TACE or TAE
- •Other experimental therapies for HCC
- •Acute variceal bleeding within the last 2 weeks
- •Large oesophageal varices ( > 5 mm diameter) without prophylactic band ligation
- •Past or current history (within the last 2 years prior to randomisation) of malignancies except for the indication under this study and curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix
- •History or evidence upon physical examination of CNS disease unless adequately treated (e.g., seizure not controlled with standard medical therapy or history of stroke within < 6 months), excluding hepatic encephalopathy
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study
- •Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants for therapeutic purposes
- •Chronic, daily treatment with aspirin (>325mg/day)
- •Pregnancy (positive serum pregnancy test) or lactation
- •Uncontrolled hypertension
- •Serious, non-healing wound, ulcer, or bone fracture
- •Currently or recent (within the 30 days prior to starting study treatment) treatment of another investigational drug or participation in another investigational study
- •Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents ( ≤ 6 months prior to study entry), myocardial infarction ( ≤ 6 months prior to study entry), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication
- •Evidence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of Sorafenib/TACE or patient at high risk from treatment complications
研究组 & 干预措施
Treatment arm
all patients will be treated with sorafenib
干预措施: Sorafenib (Drug)
Treatment arm
all patients will be treated with sorafenib
干预措施: Transarterial chemoembolisation (TACE) (Procedure)
结局指标
主要结局
Time to Progression (Efficacy)
时间窗: Until disease progression
Safety of Sorafenib in combination with TACE
时间窗: Continuously until 12 weeks after the last TACE
次要结局
未报告次要终点