Clinical trial NCT06015022: EGCG for Hepatocellular Carcinoma Chemoprevention
Official title: Phase II Randomized Controlled Trial of Epigallocatechin Gallate for Hepatocellular Carcinoma Chemoprevention
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cirrhosis, Liver
Keywords: hepatocellular carcinoma
chemoprevention
liver cancer
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2023-08-29
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized placebo-controlled trial
Primary purpose: PREVENTION

Brief summary: 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: 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).

Eligibility criteria: 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

Primary outcomes:
measure: Change in Prognostic Liver Secretome signature (PLSec) score
timeFrame: Baseline to week 24
Secondary outcomes:
measure: Complete adverse event profile
timeFrame: Baseline to week 24
measure: Change in quality of life measured by the chronic liver disease questionnaire
timeFrame: Baseline to week 24
Other outcomes:
measure: Change in hepatic gene expression-based HCC risk biomarker, Prognostic Liver Signature (PLS) (optional)
timeFrame: Baseline to week 24
measure: Change in positive signal intensities of immunohistochemistry markers (optional)
timeFrame: Baseline to week 24
measure: HCC incidence
timeFrame: Average time frame of 1 year
Locations:
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
Study officials:
affiliation: UT Southwestern
name: Yujin Hoshida, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: