Defined Green Tea Catechin Extract in Preventing Liver Cancer in Participants With Cirrhosis

NCT ID: NCT03278925

Last Updated: 2024-08-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-09
• Study Completion Date: 2024-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

Cirrhosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Prevention (defined green tea catechin extract)

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.

Group Type: EXPERIMENTAL

Biopsy

Intervention Type: PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo collection of blood samples

Computed Tomography

Intervention Type: PROCEDURE

Undergo CT

Defined Green Tea Catechin Extract

Intervention Type: DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Magnetic Resonance Imaging

Intervention Type: PROCEDURE

Undergo MRI

Pharmacological Study

Intervention Type: OTHER

Correlative studies

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Ultrasound

Intervention Type: PROCEDURE

Undergo ultrasound

Interventions

Biopsy

Undergo biopsy

Intervention Type: PROCEDURE

Biospecimen Collection

Undergo collection of blood samples

Intervention Type: PROCEDURE

Computed Tomography

Undergo CT

Intervention Type: PROCEDURE

Defined Green Tea Catechin Extract

Given PO

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Magnetic Resonance Imaging

Undergo MRI

Intervention Type: PROCEDURE

Pharmacological Study

Correlative studies

Intervention Type: OTHER

Questionnaire Administration

Ancillary studies

Intervention Type: OTHER

Ultrasound

Undergo ultrasound

Intervention Type: PROCEDURE

Other Intervention Names

BIOPSY_TYPE; Bx; Biological Sample Collection; Biospecimen Collected; Specimen Collection; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized axial tomography (procedure); Computerized Tomography; Computerized Tomography (CT) scan; CT; CT Scan; tomography; 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

Eligibility Criteria

Inclusion Criteria

• Participants with a clinical diagnosis of cirrhosis based on the investigators evaluation, confirmed by ANY ONE of the three following methods to define cirrhosis:

• Established cirrhosis on liver biopsy (Meta-analysis of Histological Data in Viral Hepatitis [METAVIR] F4);
• Ultrasound, CT or MRI findings consistent with cirrhosis; nodular appearing liver with or without evidence of portal hypertension
• Transient elastography (FibroScan) with a result > 12.5 kPa Etiology of cirrhosis will not be considered in determining inclusion in the study
• Participant is able and willing to comply with study procedures, and signed and dated informed consent is obtained
• Participant agrees to consume no more than 2 cups of green tea per day and refrain from taking supplements or foods labeled as containing green tea
• Participant must be aged >= 18 years. Because no dosing or adverse event (AE) data are currently available on the use of Polyphenon E in participants < 18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
• Platelets >= 75,000 / uL
• Hemoglobin >= 8 g/dL
• Serum creatinine OR measured or calculated creatinine clearance within normal institutional limits; glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl) within normal institutional limits as adjusted for age and sex
• Serum direct bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X upper normal level (UNL)
• Albumin >= 3.0 mg/dL
• International normalized ratio (INR) =< 1.3
• Ascites absent
• Encephalopathy absent
• Only participants found to express high levels (immunohistochemistry [IHC] score 3 and above) of gamma-OHPdG (gamma-OHPdG-high HCC) in baseline or archival liver biopsy will be registered to receive Polyphenon E treatment
• Participant is able to undergo radiographic evaluation with ultrasound, CT, or MRI
• The effects of Polyphenon E on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence); contraception must be used prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately; female participants of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication (if a urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required)

Exclusion Criteria

• Participant has confirmed HCC by ultrasound/CT/MRI; participants who have previously had HCC but have been treated and have been recurrence free for 5 years are eligible
• Participant has or has had other cancer(s) within 3 years of study; however, in situ breast, in situ cervical, and basal cell/squamous cell skin cancers are allowed; participant with active, other cancer that requires systemic therapy will be excluded from this study; participant with early stage cancer that requires local therapy, such as cervical ablation for early stage cervical cancer, are allowed to be registered in the study and are allowed to receive local therapy
• Inability to swallow capsules
• Participant has a known diagnosis of mental incapacitation that may affect their ability to consent and be compliant with the protocol
• Participant has ever experienced one or more hepatic decompensation events or a history of decompensated liver disease as listed below:

• Clinical ascites
• Variceal bleeding documented by endoscopy
• Spontaneous bacterial peritonitis documented by positive culture
• Hepatic encephalopathy
• Hepatorenal syndrome (type 1 or 2)
• Porto-pulmonary hypertension
• Hepato-pulmonary hypertension
• Any liver-related event which led to a hospitalization or a grade 4 event
• Participant has an underlying predisposition to gastrointestinal (GI) or rectal bleeding are considered ineligible for study participation
• History of allergic reactions attributed to compounds of similar chemical composition to Polyphenon E (or green tea); note that participants who are unable to tolerate intravenous contrast for CT scans should have MRIs or ultrasounds during the study instead of CT scans
• Participant is receiving any other investigational agents
• Participants have taken supplements or foods that are labelled as containing green tea for 8 weeks before start of treatment
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; hepatitis b virus (HBV) and hepatitis C virus (HCV) infections are allowed
• Green tea has been consumed by humans for thousands of years and teratogenic or abortifacient effects have not been reported; however, subjects in this study will take high doses of Polyphenon E; the teratogenic or abortifacient effects of high dose Polyphenon E is unknown; therefore pregnant women are excluded from this study; because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with Polyphenon E, breastfeeding should be discontinued if the mother is treated with this study agent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Aiwu R He

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

University of Puerto Rico

San Juan, , Puerto Rico

Countries

United States; Puerto Rico

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2017-01557

Identifier Type: REGISTRY

Identifier Source: secondary_id

N01-CN-2012-00035

Identifier Type: -

Identifier Source: secondary_id

NCI 2016-08-02

Identifier Type: OTHER

Identifier Source: secondary_id

NWU2016-08-02

Identifier Type: OTHER

Identifier Source: secondary_id

N01CN00035

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA060553

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2017-01557

Identifier Type: -

Identifier Source: org_study_id