<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03278925</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2017-01557</org_study_id>
    <secondary_id>NCI-2017-01557</secondary_id>
    <secondary_id>N01-CN-2012-00035</secondary_id>
    <secondary_id>NCI 2016-08-02</secondary_id>
    <secondary_id>NWU2016-08-02</secondary_id>
    <secondary_id>N01CN00035</secondary_id>
    <secondary_id>P30CA060553</secondary_id>
    <nct_id>NCT03278925</nct_id>
  </id_info>
  <brief_title>Defined Green Tea Catechin Extract in Preventing Liver Cancer in Participants With Cirrhosis</brief_title>
  <official_title>A Phase I Single-arm, Multicenter Pilot Study Aimed at Validating γ-OHPdG as a Biomarker and Testing the Effects of Polyphenon E on Its Levels in Patients With Cirrhosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the side effects and best dose of defined green tea catechin&#xD;
      extract and to see how well it works in preventing liver cancer in participants with&#xD;
      cirrhosis. Higher levels of the molecule gamma-OHPdG may be found in participants with&#xD;
      cirrhosis, which may mean a higher risk of the development of liver cancer. Defined green tea&#xD;
      catechin extract may work better to lower levels of gamma-OHPdG and prevent the development&#xD;
      of liver cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To establish maximum tolerated dose (MTD) and to collect safety data of defined green tea&#xD;
      catechin extract (Polyphenon E/epigallocatechin gallate [EGCG]) treatment in participants&#xD;
      with cirrhosis.&#xD;
&#xD;
      II. To determine the effects of Polyphenon E/EGCG treatment on the suppression of&#xD;
      gamma-hydroxy-1,N(2)-propanodeoxyguanosine (gamma-OHPdG) levels in cirrhotic liver.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To collect Polyphenon E/EGCG pharmacokinetic data in participants with cirrhosis.&#xD;
&#xD;
      II. To determine the effects of Polyphenon E/EGCG treatment on the suppression of&#xD;
      gamma-hydroxy-1,N(2)-propanodeoxyguanosine (gamma-OHPdG) levels in cirrhotic liver by liquid&#xD;
      chromatography-mass spectrometry (LC-MS) assay from baseline to post-treatment.&#xD;
&#xD;
      III. To estimate the fraction of participants with liver cirrhosis that have high levels of&#xD;
      gamma-OHPdG.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To assess the effects of Polyphenon E/EGCG on the grade of cirrhosis as measured by&#xD;
      FibroScan (registered trademark) and Fibrosis-4 (FIB-4) score.&#xD;
&#xD;
      II. To develop a LC-MS and/or enzyme-linked immunosorbent assay (ELISA)-based method for&#xD;
      detecting urinary and blood gamma-OHPdG, to correlate with liver gamma-OHPdG levels.&#xD;
&#xD;
      III. To evaluate any hepatocellular carcinoma (HCC) development during the treatment.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study.&#xD;
&#xD;
      Participants receive defined green tea catechin extract orally (PO) once daily (QD) or twice&#xD;
      daily (BID) for 24 weeks in the absence of disease progression or unacceptable toxicity.&#xD;
      Patients undergo ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) at&#xD;
      screening and on study, undergo collection of blood samples on study, and may undergo biopsy&#xD;
      at screening and on study.&#xD;
&#xD;
      After completion of study intervention, participants are followed up at 28 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 9, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Actual">June 16, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum tolerated dose of Polyphenon E</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>Will be defined as the dose at which =&lt; 1 subjects out of 6 experiences a grade 3 or higher toxicity based on Common Terminology Criteria for Adverse Events criteria.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in gamma-hydroxy-1,N(2)-propanodeoxyguanosine (gamma-OHPdG) expression in cirrhotic liver</measure>
    <time_frame>Baseline up to 24 weeks</time_frame>
    <description>Will be assessed by immunohistochemistry. Will use a nonparametric Wilcoxon test to compare the post-pre differences to zero.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Fraction of patients with liver cirrhosis that have high levels of gamma-OHPdG</measure>
    <time_frame>Up to 24 weeks</time_frame>
    <description>Will use descriptive statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in gamma-OHPdG</measure>
    <time_frame>Baseline up to 24 weeks</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Polyphenon E pharmacokinetic data in blood and urine in patients with cirrhosis</measure>
    <time_frame>Prior to and at 1.5, 3.5, and 8.5 hours after the first dose of Polyphenon E on day 1</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Grade of cirrhosis</measure>
    <time_frame>Up to 24 weeks</time_frame>
    <description>Will be assessed by FibroScan and Fibrosis-4 score.</description>
  </other_outcome>
  <other_outcome>
    <measure>Liquid chromatography-mass spectrometry (LC-MS) and/or enzyme-linked immunosorbent assay (ELISA)-based method for detecting gamma-OHPdG</measure>
    <time_frame>Up to 24 weeks</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Incidence of hepatocellular carcinoma</measure>
    <time_frame>At baseline and 24 weeks</time_frame>
    <description>Evaluated using ultrasound/computed tomography/magnetic resonance imaging.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Cirrhosis</condition>
  <arm_group>
    <arm_group_label>Prevention (defined green tea catechin extract)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Biopsy</intervention_name>
    <description>Undergo biopsy</description>
    <arm_group_label>Prevention (defined green tea catechin extract)</arm_group_label>
    <other_name>BIOPSY_TYPE</other_name>
    <other_name>Bx</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Biospecimen Collection</intervention_name>
    <description>Undergo collection of blood samples</description>
    <arm_group_label>Prevention (defined green tea catechin extract)</arm_group_label>
    <other_name>Biological Sample Collection</other_name>
    <other_name>Biospecimen Collected</other_name>
    <other_name>Specimen Collection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Computed Tomography</intervention_name>
    <description>Undergo CT</description>
    <arm_group_label>Prevention (defined green tea catechin extract)</arm_group_label>
    <other_name>CAT</other_name>
    <other_name>CAT Scan</other_name>
    <other_name>Computed Axial Tomography</other_name>
    <other_name>Computerized Axial Tomography</other_name>
    <other_name>Computerized axial tomography (procedure)</other_name>
    <other_name>Computerized Tomography</other_name>
    <other_name>CT</other_name>
    <other_name>CT Scan</other_name>
    <other_name>tomography</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Defined Green Tea Catechin Extract</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Prevention (defined green tea catechin extract)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Prevention (defined green tea catechin extract)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Magnetic Resonance Imaging</intervention_name>
    <description>Undergo MRI</description>
    <arm_group_label>Prevention (defined green tea catechin extract)</arm_group_label>
    <other_name>Magnetic Resonance</other_name>
    <other_name>Magnetic resonance imaging (procedure)</other_name>
    <other_name>Magnetic Resonance Imaging Scan</other_name>
    <other_name>Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance</other_name>
    <other_name>MR</other_name>
    <other_name>MR Imaging</other_name>
    <other_name>MRI</other_name>
    <other_name>MRI Scan</other_name>
    <other_name>NMR Imaging</other_name>
    <other_name>NMRI</other_name>
    <other_name>Nuclear Magnetic Resonance Imaging</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharmacological Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Prevention (defined green tea catechin extract)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire Administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Prevention (defined green tea catechin extract)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Ultrasound</intervention_name>
    <description>Undergo ultrasound</description>
    <arm_group_label>Prevention (defined green tea catechin extract)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants with a clinical diagnosis of cirrhosis based on the investigators&#xD;
             evaluation, confirmed by ANY ONE of the three following methods to define cirrhosis:&#xD;
&#xD;
               -  Established cirrhosis on liver biopsy (Meta-analysis of Histological Data in&#xD;
                  Viral Hepatitis [METAVIR] F4);&#xD;
&#xD;
               -  Ultrasound, CT or MRI findings consistent with cirrhosis; nodular appearing liver&#xD;
                  with or without evidence of portal hypertension&#xD;
&#xD;
               -  Transient elastography (FibroScan) with a result &gt; 12.5 kPa Etiology of cirrhosis&#xD;
                  will not be considered in determining inclusion in the study&#xD;
&#xD;
          -  Participant is able and willing to comply with study procedures, and signed and dated&#xD;
             informed consent is obtained&#xD;
&#xD;
          -  Participant agrees to consume no more than 2 cups of green tea per day and refrain&#xD;
             from taking supplements or foods labeled as containing green tea&#xD;
&#xD;
          -  Participant must be aged &gt;= 18 years. Because no dosing or adverse event (AE) data are&#xD;
             currently available on the use of Polyphenon E in participants &lt; 18 years of age,&#xD;
             children are excluded from this study but will be eligible for future pediatric&#xD;
             trials, if applicable&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 1 (Karnofsky &gt;= 70%)&#xD;
&#xD;
          -  Platelets &gt;= 75,000 / uL&#xD;
&#xD;
          -  Hemoglobin &gt;= 8 g/dL&#xD;
&#xD;
          -  Serum creatinine OR measured or calculated creatinine clearance within normal&#xD;
             institutional limits; glomerular filtration rate (GFR) can also be used in place of&#xD;
             creatinine or creatinine clearance (CrCl) within normal institutional limits as&#xD;
             adjusted for age and sex&#xD;
&#xD;
          -  Serum direct bilirubin within normal institutional limits&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and&#xD;
             alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =&lt; 2.5 X&#xD;
             upper normal level (UNL)&#xD;
&#xD;
          -  Albumin &gt;= 3.0 mg/dL&#xD;
&#xD;
          -  International normalized ratio (INR) =&lt; 1.3&#xD;
&#xD;
          -  Ascites absent&#xD;
&#xD;
          -  Encephalopathy absent&#xD;
&#xD;
          -  Only participants found to express high levels (immunohistochemistry [IHC] score 3 and&#xD;
             above) of gamma-OHPdG (gamma-OHPdG-high HCC) in baseline or archival liver biopsy will&#xD;
             be registered to receive Polyphenon E treatment&#xD;
&#xD;
          -  Participant is able to undergo radiographic evaluation with ultrasound, CT, or MRI&#xD;
&#xD;
          -  The effects of Polyphenon E on the developing human fetus at the recommended&#xD;
             therapeutic dose are unknown; for this reason, women of child-bearing potential and&#xD;
             men must agree to use adequate contraception (hormonal or barrier method of birth&#xD;
             control; abstinence); contraception must be used prior to study entry and for the&#xD;
             duration of study participation; should a woman become pregnant or suspect she is&#xD;
             pregnant while participating in this study, she should inform her study physician&#xD;
             immediately; female participants of childbearing potential should have a negative&#xD;
             urine or serum pregnancy test within 72 hours prior to receiving the first dose of&#xD;
             study medication (if a urine test is positive or cannot be confirmed as negative, a&#xD;
             serum pregnancy test will be required)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participant has confirmed HCC by ultrasound/CT/MRI; participants who have previously&#xD;
             had HCC but have been treated and have been recurrence free for 5 years are eligible&#xD;
&#xD;
          -  Participant has or has had other cancer(s) within 3 years of study; however, in situ&#xD;
             breast, in situ cervical, and basal cell/squamous cell skin cancers are allowed;&#xD;
             participant with active, other cancer that requires systemic therapy will be excluded&#xD;
             from this study; participant with early stage cancer that requires local therapy, such&#xD;
             as cervical ablation for early stage cervical cancer, are allowed to be registered in&#xD;
             the study and are allowed to receive local therapy&#xD;
&#xD;
          -  Inability to swallow capsules&#xD;
&#xD;
          -  Participant has a known diagnosis of mental incapacitation that may affect their&#xD;
             ability to consent and be compliant with the protocol&#xD;
&#xD;
          -  Participant has ever experienced one or more hepatic decompensation events or a&#xD;
             history of decompensated liver disease as listed below:&#xD;
&#xD;
               -  Clinical ascites&#xD;
&#xD;
               -  Variceal bleeding documented by endoscopy&#xD;
&#xD;
               -  Spontaneous bacterial peritonitis documented by positive culture&#xD;
&#xD;
               -  Hepatic encephalopathy&#xD;
&#xD;
               -  Hepatorenal syndrome (type 1 or 2)&#xD;
&#xD;
               -  Porto-pulmonary hypertension&#xD;
&#xD;
               -  Hepato-pulmonary hypertension&#xD;
&#xD;
               -  Any liver-related event which led to a hospitalization or a grade 4 event&#xD;
&#xD;
          -  Participant has an underlying predisposition to gastrointestinal (GI) or rectal&#xD;
             bleeding are considered ineligible for study participation&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical composition&#xD;
             to Polyphenon E (or green tea); note that participants who are unable to tolerate&#xD;
             intravenous contrast for CT scans should have MRIs or ultrasounds during the study&#xD;
             instead of CT scans&#xD;
&#xD;
          -  Participant is receiving any other investigational agents&#xD;
&#xD;
          -  Participants have taken supplements or foods that are labelled as containing green tea&#xD;
             for 8 weeks before start of treatment&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements; hepatitis b virus (HBV) and hepatitis C virus (HCV) infections are&#xD;
             allowed&#xD;
&#xD;
          -  Green tea has been consumed by humans for thousands of years and teratogenic or&#xD;
             abortifacient effects have not been reported; however, subjects in this study will&#xD;
             take high doses of Polyphenon E; the teratogenic or abortifacient effects of high dose&#xD;
             Polyphenon E is unknown; therefore pregnant women are excluded from this study;&#xD;
             because there is an unknown but potential risk for AEs in nursing infants secondary to&#xD;
             treatment of the mother with Polyphenon E, breastfeeding should be discontinued if the&#xD;
             mother is treated with this study agent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Aiwu R He</last_name>
    <role>Principal Investigator</role>
    <affiliation>Northwestern University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>MedStar Georgetown University Hospital</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Puerto Rico</name>
      <address>
        <city>San Juan</city>
        <zip>00936</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Puerto Rico</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>September 11, 2017</study_first_submitted>
  <study_first_submitted_qc>September 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>August 2, 2023</last_update_submitted>
  <last_update_submitted_qc>August 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epigallocatechin gallate</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03278925
org study id: NCI-2017-01557
secondary id: NCI-2017-01557
secondary id: N01-CN-2012-00035
secondary id: NCI 2016-08-02
secondary id: NWU2016-08-02
secondary id: N01CN00035
secondary id: P30CA060553
nct id: NCT03278925
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Maximum tolerated dose of Polyphenon E
time frame: Up to 4 weeks
description: 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.
measure: Change in gamma-hydroxy-1,N(2)-propanodeoxyguanosine (gamma-OHPdG) expression in cirrhotic liver
time frame: Baseline up to 24 weeks
description: Will be assessed by immunohistochemistry. Will use a nonparametric Wilcoxon test to compare the post-pre differences to zero.
measure: Fraction of patients with liver cirrhosis that have high levels of gamma-OHPdG
time frame: Up to 24 weeks
description: Will use descriptive statistics.
measure: Change in gamma-OHPdG
time frame: Baseline up to 24 weeks
description: 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.
measure: Polyphenon E pharmacokinetic data in blood and urine in patients with cirrhosis
time frame: Prior to and at 1.5, 3.5, and 8.5 hours after the first dose of Polyphenon E on day 1
description: 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.
measure: Grade of cirrhosis
time frame: Up to 24 weeks
description: Will be assessed by FibroScan and Fibrosis-4 score.
measure: Liquid chromatography-mass spectrometry (LC-MS) and/or enzyme-linked immunosorbent assay (ELISA)-based method for detecting gamma-OHPdG
time frame: Up to 24 weeks
description: 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.
measure: Incidence of hepatocellular carcinoma
time frame: At baseline and 24 weeks
description: Evaluated using ultrasound/computed tomography/magnetic resonance imaging.
arm group label: Prevention (defined green tea catechin extract)
arm group type: Experimental
description: 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.
intervention type: Procedure
intervention name: Biopsy
description: Undergo biopsy
arm group label: Prevention (defined green tea catechin extract)
other name: BIOPSY_TYPE
other name: Bx
intervention type: Procedure
intervention name: Biospecimen Collection
description: Undergo collection of blood samples
arm group label: Prevention (defined green tea catechin extract)
other name: Biological Sample Collection
other name: Biospecimen Collected
other name: Specimen Collection
intervention type: Procedure
intervention name: Computed Tomography
description: Undergo CT
arm group label: Prevention (defined green tea catechin extract)
other name: CAT
other name: CAT Scan
other name: Computed Axial Tomography
other name: Computerized Axial Tomography
other name: Computerized axial tomography (procedure)
other name: Computerized Tomography
other name: CT
other name: CT Scan
other name: tomography
intervention type: Drug
intervention name: Defined Green Tea Catechin Extract
description: Given PO
arm group label: Prevention (defined green tea catechin extract)
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Prevention (defined green tea catechin extract)
intervention type: Procedure
intervention name: Magnetic Resonance Imaging
description: Undergo MRI
arm group label: Prevention (defined green tea catechin extract)
other name: Magnetic Resonance
other name: Magnetic resonance imaging (procedure)
other name: Magnetic Resonance Imaging Scan
other name: Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
other name: MR
other name: MR Imaging
other name: MRI
other name: MRI Scan
other name: NMR Imaging
other name: NMRI
other name: Nuclear Magnetic Resonance Imaging
intervention type: Other
intervention name: Pharmacological Study
description: Correlative studies
arm group label: Prevention (defined green tea catechin extract)
intervention type: Other
intervention name: Questionnaire Administration
description: Ancillary studies
arm group label: Prevention (defined green tea catechin extract)
intervention type: Procedure
intervention name: Ultrasound
description: Undergo ultrasound
arm group label: Prevention (defined green tea catechin extract)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Aiwu R He
role: Principal Investigator
affiliation: Northwestern University
facility: 
facility: 
country: Puerto Rico
country: United States
responsible party type: Sponsor
mesh term: Liver Cirrhosis
mesh term: Fibrosis
mesh term: Epigallocatechin gallate