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

NCT03278925 | Active Not Recruiting Phase 1 DMC FDA Drug

• 6 other identifiers: NCI-2017-01557N01-CN-2012-00035NCI 2016-08-02NWU2016-08-02N01CN00035P30CA060553
• Study Type: interventional
• Target: 14
• Locations: 2 countries
• Sites: 2

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.

Conditions

Cirrhosis

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Baseline up to 24 weeks

Secondary Outcomes (3)

• Fraction of patients with liver cirrhosis that have high levels of gamma-OHPdG

  Up to 24 weeks

• Change in gamma-OHPdG

  Baseline up to 24 weeks

• Polyphenon E pharmacokinetic data in blood and urine in patients with cirrhosis

  Prior to and at 1.5, 3.5, and 8.5 hours after the first dose of Polyphenon E on day 1

Other Outcomes (3)

• Grade of cirrhosis

  Up to 24 weeks

• Liquid chromatography-mass spectrometry (LC-MS) and/or enzyme-linked immunosorbent assay (ELISA)-based method for detecting gamma-OHPdG

  Up to 24 weeks

• Incidence of hepatocellular carcinoma

  At baseline and 24 weeks

Study Arms (1)

Prevention (defined green tea catechin extract)

EXPERIMENTAL

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

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Prevention (defined green tea catechin extract)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Prevention (defined green tea catechin extract)

Computed Tomography PROCEDURE

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

Prevention (defined green tea catechin extract)

Defined Green Tea Catechin Extract DRUG

Given PO

Prevention (defined green tea catechin extract)

Laboratory Biomarker Analysis OTHER

Correlative studies

Prevention (defined green tea catechin extract)

Magnetic Resonance Imaging PROCEDURE

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

Prevention (defined green tea catechin extract)

Pharmacological Study OTHER

Correlative studies

Prevention (defined green tea catechin extract)

Questionnaire Administration OTHER

Ancillary studies

Prevention (defined green tea catechin extract)

Ultrasound PROCEDURE

Undergo ultrasound

Prevention (defined green tea catechin extract)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

University of Puerto Rico

San Juan, 00936, Puerto Rico

Location

MeSH Terms

Conditions

Fibrosis

Interventions

Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; High-Energy Shock Waves

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Ultrasonic Waves; Sound; Radiation, Nonionizing; Radiation; Physical Phenomena

Study Officials

• Aiwu R He

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2017
• First Posted: September 12, 2017
• Study Start: August 9, 2018
• Primary Completion: June 16, 2023
• Study Completion: December 31, 2024
• Last Updated: August 2, 2024

Record last verified: 2024-07

Locations

US (1); PR (1)