EGCG for Hepatocellular Carcinoma Chemoprevention

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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Phase II Randomized Controlled Trial of Epigallocatechin Gallate for Hepatocellular Carcinoma Chemoprevention

Conditions
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Cirrhosis, Liver

Intervention / Treatment
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* Drug: Epigallocatechin gallate (EGCG)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized placebo-controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epigallocatechin gallate 600 - 800mg<br>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. | Drug: Epigallocatechin gallate (EGCG)<br>* EGCG is a green tea-derived catechin<br>* Other names: Teavigo;|
| Placebo Comparator: Placebo<br>Oral administration of placebo for 24 weeks | Other: Placebo<br>* Placebo in the same capsule with the experimental agent (EGCG).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Prognostic Liver Secretome signature (PLSec) score | 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. | Baseline to week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete adverse event profile | Adverse events are monitored at least monthly and graded/recorded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5. The number and severity of adverse events will be tabulated and summarized across all grades. Grade 3+ adverse events will be similarly described and summarized separately. | Baseline to week 24 | 
| Change in quality of life measured by the chronic liver disease questionnaire | Quality of life (QOL) will be measured by using the chronic liver disease questionnaire (CLDQ), which consists of 29 questions. Participants can select one answer from seven choices of descriptive answers for each question. Frequency distributions, graphical techniques and other descriptive measures will be used to summarize the results. When frequencies are compared, Fisher's exact test will be used. | Baseline to week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatocellular carcinoma, chemoprevention