NCT00390195Unknown1 期
Randomized Phase I/II of Rapamycin Analog, RAD001, in Advanced Hepatocellular Carcinoma - With a Pharmacokinetic Study of RAD001
National Health Research Institutes, Taiwan2 个研究点 分布在 1 个国家目标入组 134 人开始时间: 2006年10月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 134
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose in Phase I
研究概览
简要总结
The mTOR has been examined in hepatocellular carcinomas as well. This pathway is up-regulated in a proportion of hepatocellular carcinoma (HCC) and that rapamycin inhibits cell proliferation and blocks S6K phosphorylation. Inhibition of mTOR had been shown to suppress substantially the liver tumor growth. Nevertheless, inhibition of mTOR was demonstrated to have a clinical response in some cancer types. These reports imply that inhibition of mTOR could be a promising therapeutic strategy in the treatment of HCC. Therefore, we hypothesize that RAD001, a rapamycin analog, can inhibit the mTOR, and subsequently suppress the liver tumor in the treatment of HCC patients.
This study is aimed to investigate the safety, efficacy, pharmacokinetics, pharmacogenetics and feasibility of RAD001 in advanced HCC patients. This study will be a randomized phase I study with dose escalation and subsequently a phase II study of intent to treat, as well as pharmacokinetic, pharmacogenetic and surrogate marker study of RAD001.
详细描述
Objectives：
- Primary Objectives
- Phase I: To assess the maximal tolerated dose (MTD) of once daily and weekly oral RAD001 in patients with advanced HCC of Child-Pugh's class A or B
- Phase II: To assess the disease control rate of advanced Child-Pugh's class A or B HCC patients receiving the determined MTD of once daily and weekly oral RAD001 in phase I
- Secondary Objectives
- Phase I: To investigate the following items in the advanced HCC patients receiving RAD001
- Dose-limiting toxicity
- Pharmacokinetics study
- Pharmacogenetic study
- Surrogate marker study on the PTEN, total and Phosphorylated forms of Akt of tumor tissues
- Disease control rate
- Phase II: To investigate the following items in the advanced HCC patients receiving RAD001
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with measurable, metastatic or locally advanced HCC that are not feasible to have or have failed to prior local therapy (including surgical resection, transarterial chemoembolization and/or alcohol injection) are eligible.
- •The diagnosis of HCC should be established either by cyto/histology; or, by characteristic imaging studies (have to including angiography) plus serum level of AFP equal to or more than 400 ng/mL in patients with cirrhosis of the liver and/or chronic viral hepatitis B or C infection.
- •Patients must be equal to or more than 20 years of age and equal or less than 75 years of age.
- •Patients must have a performance status of ECOG score equal to or less than
- •Patients must fulfill all of the following criteria: Child-Pugh's Score equal to or less than 9; serum total bilirubin level is equal to or less than 2.0 mg/dL; serum ALT level (GPT) equal to or less than 3.0 x upper normal limit; platelet are equal to or more than 50,000 / uL; WBC are equal to or more than 3,000 / uL.
- •Serum creatinine equal to or less than 2.0 x upper normal limit.
- •Life expectancy equal to or more than 12 weeks.
- •Signed informed consent.
- •Sexually active patients, in conjunction with their partner, must practice birth control during, and for 2 months after therapy.
- •Female patients at child-bearing age must have negative pregnancy test.
- •No known HIV infection.
排除标准
- •Patients with diseases which require concurrent usage of glucocorticosteroid or immunosuppressant agent(s) are not eligible.
- •Patients with concomitant active secondary malignancies, except for surgically cured carcinoma in situ of the cervix and basal or adequately treated squamous cell carcinoma of the skin, or disease-free of malignancies < 3 years before the study, are not eligible.
- •Patients with active infection are not eligible.
- •Patients who received other rapamycin analogs before are not eligible.
- •Patients with severe cardiopulmonary diseases (including history of stable, effort-induced or unstable angina pectoris or myocardiac infarction) and other systemic diseases under poor control are not eligible.
- •Patients with history of psychiatric disorder are not eligible.
- •Patients with brain metastases are not eligible.
- •Patients who received surgery, radiotherapy except to bone, chemotherapy, immunotherapy, or other investigational drug within 4 weeks before initiating study are not eligible.
- •Patients who are pregnant, breast-feeding or not using appropriate birth control during the course of the study are not eligible.
- •Patients with significant concomitant disease that will be aggravated by the investigational drug are not eligible.
- •Patients on active treatment with inhibitors or inducers of P-glycoprotein, CYP3A4 and CYP3A5 are not eligible; a minimal of 2 weeks wash-out period will be required after stop such medications.
研究组 & 干预措施
1. Daily
Experimental
Taking orally the investigational drug daily
干预措施: RAD001 (everolimus) (Drug)
2. Weekly
Experimental
Taking orally the investigational drug weekly
干预措施: RAD001 (everolimus) (Drug)
结局指标
主要结局
Maximum tolerated dose in Phase I
时间窗: June-2008
Disease control rate in Phase II
时间窗: Dec-2009
次要结局
- Overall survival(Jun-2010)
- Time to tumor progression(Jun-2010)
- Pharmacokinetics(Jun-2008)
- Pharmacodynamics(Dec-2009)
- Angiogenic factors(Dec-2009)
- Pharmacogenetics(Dec-2009)
- Tumor marker(Dec-2009)
研究者
研究点 (2)
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