A Phase 1 interventional study of Biopsy and Biospecimen Collection in Cirrhosis, sponsored by National Cancer Institute (NCI). Active, not recruiting at 2 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-08-02.
Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Prevention
This phase I trial studies the side effects and best dose of defined green tea catechin extract and to see how well it works in preventing liver cancer in participants with cirrhosis. Higher levels of the molecule gamma-OHPdG may be found in participants with cirrhosis, which may mean a higher risk of the development of liver cancer. Defined green tea catechin extract may work better to lower levels of gamma-OHPdG and prevent the development of liver cancer.
PRIMARY OBJECTIVES:
I. To establish maximum tolerated dose (MTD) and to collect safety data of defined green tea catechin extract (Polyphenon E/epigallocatechin gallate [EGCG]) treatment in participants with cirrhosis.
II. To determine the effects of Polyphenon E/EGCG treatment on the suppression of gamma-hydroxy-1,N(2)-propanodeoxyguanosine (gamma-OHPdG) levels in cirrhotic liver.
SECONDARY OBJECTIVES:
I. To collect Polyphenon E/EGCG pharmacokinetic data in participants with cirrhosis.
II. To determine the effects of Polyphenon E/EGCG treatment on the suppression of gamma-hydroxy-1,N(2)-propanodeoxyguanosine (gamma-OHPdG) levels in cirrhotic liver by liquid chromatography-mass spectrometry (LC-MS) assay from baseline to post-treatment.
III. To estimate the fraction of participants with liver cirrhosis that have high levels of gamma-OHPdG.
EXPLORATORY OBJECTIVES:
I. To assess the effects of Polyphenon E/EGCG on the grade of cirrhosis as measured by FibroScan (registered trademark) and Fibrosis-4 (FIB-4) score.
II. To develop a LC-MS and/or enzyme-linked immunosorbent assay (ELISA)-based method for detecting urinary and blood gamma-OHPdG, to correlate with liver gamma-OHPdG levels.
III. To evaluate any hepatocellular carcinoma (HCC) development during the treatment.
OUTLINE: This is a dose-escalation study.
Participants receive defined green tea catechin extract orally (PO) once daily (QD) or twice daily (BID) for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) at screening and on study, undergo collection of blood samples on study, and may undergo biopsy at screening and on study.
After completion of study intervention, participants are followed up at 28 days.
Participants with a clinical diagnosis of cirrhosis based on the investigators evaluation, confirmed by ANY ONE of the three following methods to define cirrhosis:
Exclusion Criteria:
Participant has ever experienced one or more hepatic decompensation events or a history of decompensated liver disease as listed below:
Participants receive defined green tea catechin extract PO QD or BID for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo ultrasound, CT, or MRI at screening and on study, undergo collection of blood samples on study, and may undergo biopsy at screening and on study.
Procedure: Biopsy · Procedure: Biospecimen Collection · Procedure: Computed Tomography · Drug: Defined Green Tea Catechin Extract · Other: Laboratory Biomarker Analysis · Procedure: Magnetic Resonance Imaging · Other: Pharmacological Study · Other: Questionnaire Administration · Procedure: Ultrasound
Undergo biopsy
Also known as: BIOPSY_TYPE, Bx
Undergo collection of blood samples
Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo CT
Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography
Given PO
Correlative studies
Undergo MRI
Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI
Correlative studies
Ancillary studies
Undergo ultrasound
Maximum tolerated dose of Polyphenon E
Will be defined as the dose at which =\< 1 subjects out of 6 experiences a grade 3 or higher toxicity based on Common Terminology Criteria for Adverse Events criteria.
Time frame: Up to 4 weeks
Change in gamma-hydroxy-1,N(2)-propanodeoxyguanosine (gamma-OHPdG) expression in cirrhotic liver
Will be assessed by immunohistochemistry. Will use a nonparametric Wilcoxon test to compare the post-pre differences to zero.
Time frame: Baseline up to 24 weeks
Fraction of patients with liver cirrhosis that have high levels of gamma-OHPdG
Will use descriptive statistics.
Time frame: Up to 24 weeks
Change in gamma-OHPdG
Descriptive statistics (mean, range) will be used to summarize this continuous outcome by dose level. A nonparametric trend test will be used to examine whether there is a trend for greater reduction in gamma-OHPdG as the dose level increases.
Time frame: Baseline up to 24 weeks
Polyphenon E pharmacokinetic data in blood and urine in patients with cirrhosis
Clearance of Polyphenon E will be compared among cirrhotic liver patients in this study and results from this population will be compared with non-cirrhotic historical control participants.
Time frame: Prior to and at 1.5, 3.5, and 8.5 hours after the first dose of Polyphenon E on day 1
Grade of cirrhosis
Will be assessed by FibroScan and Fibrosis-4 score.
Time frame: Up to 24 weeks
Liquid chromatography-mass spectrometry (LC-MS) and/or enzyme-linked immunosorbent assay (ELISA)-based method for detecting gamma-OHPdG
The research urine samples at screen 2 and research blood samples collected at visit 1, visit 2, and Visit 3 will be used to develop a non-invasive LC-MS and/or ELISA-based method to quantify gamma-OHPdG in urine and blood samples of collected from trial participants. Descriptive statistics (n; minimum; maximum; mean; median; standard deviation for continuous variables; and n, frequency for categorical variables) will be used to summarize participants demographics. Participants safety data will be tabulated according to the symptom and grade. Estimates will be presented with their 95% confidence intervals.
Time frame: Up to 24 weeks
Incidence of hepatocellular carcinoma
Evaluated using ultrasound/computed tomography/magnetic resonance imaging.
Time frame: At baseline and 24 weeks
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National Cancer Institute (NCI)