Phase II Randomized Controlled Trial of Epigallocatechin Gallate for Hepatocellular Carcinoma Chemoprevention
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change in Prognostic Liver Secretome signature (PLSec) score
研究概览
简要总结
This phase II trial tests epigallocatechin gallate (EGCG) for its efficacy and safety in preventing development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis.
详细描述
This study will evaluate whether EGCG favorably modulate an HCC risk biomarker (PLSec) with acceptable safety profile in patients with compensated cirrhosis and elevated HCC risk determined by clinical variable-based score (FIB-4 index) and PLSec. Sixty participants will be randomized (1:1) to either the study drub or placebo arm and receive the treatment for 24 weeks. The participants will orally take EGCG 600 mg capsules or placebo for the first 12 weeks. If an interim PLSec analysis at the end of week 8 is not improved without any dose-limiting adverse events, the dose will be increased to 800 mg for the second 12 weeks. If the interim PLSec is improved, 600 mg will be continued. After completing the 24-week treatment, change in the PLSec test with the treatment is calculated by comparing pre- and post-treatment serum samples in each patient, and the changes will be compared between the treatment arms (primary endpoint). Complete adverse event profiles will be recorded, and change in quality of life will be compared between the treatment arms (secondary endpoints). If optional paired liver biopsy tissues are obtained, changes in tissue-based HCC risk biomarker (PLS) and immunohistochemical markers of cell proliferation, neoplasm, senescence, and fibrogenesis will be determined, changes in the FIB-4 index and liver stiffness measurement will be determined, and association with incident HCC during the study period will be evaluated (exploratory endpoints).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blinded
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
- •Adults (≥ 18 years-old)
- •Clinically and/or histologically diagnosed cirrhosis
- •No active hepatic decompensation
- •No prior history of HCC
- •Adequate hematologic, hepatic, and renal function
- •Karnofsky performance status score ≥70
- •Both sexes and all racial/ethnic groups will be considered
- •FIB-4 index > 3.25
- •High-risk PLSec at baseline
- •Absence of HLA-B*35:01
排除标准
- •Prior or ongoing use of EGCG
- •History of adverse reaction to green tea products
- •Severe obesity (BMI > 40 kg/m2)
- •Active drinking
- •EGCG treatment <4 weeks or <80% of planned regimen at the end of week 4
- •HCC development during the study
研究组 & 干预措施
Epigallocatechin gallate 600 - 800mg
Epigallocatechin gallate (EGCG) 600mg will be administered daily via oral route for the initial 12 consecutive weeks on an outpatient basis. The dose of 600 mg will be continued for the second 12 weeks if an interim HCC biomarker test at the end of week 8 improves. If the interim test does not improve without dose-limiting adverse events, the dose will be increased to 800mg for the second 12 weeks, All participants will receive 24 weeks of treatment in total.
干预措施: Epigallocatechin gallate (EGCG) (Drug)
Placebo
Oral administration of placebo for 24 weeks
干预措施: Placebo (Other)
结局指标
主要结局
Change in Prognostic Liver Secretome signature (PLSec) score
时间窗: Baseline to week 24
HCC risk level at baseline and post-treatment will be determined as Prognostic Liver Secretome signature (PLSec) score, ranging from 0 (lowest risk) to 8 (highest risk). Change in the biomarker-based HCC risk level will be calculated as delta-PLSec by subtracting the post-treatment PLSec score from the baseline pre-treatment PLSec score. delta-PLSec values will be compared between the EGCG and placebo arms using two-sample t-test.
次要结局
- Complete adverse event profile(Baseline to week 24)
- Change in quality of life measured by the chronic liver disease questionnaire(Baseline to week 24)
研究者
Yujin Hoshida, MD, PhD
Professor
University of Texas Southwestern Medical Center