xml: <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/NCT06015022</url>
    </required_header>
    <id_info>
      <org_study_id>STU-2023-0233</org_study_id>
      <nct_id>NCT06015022</nct_id>
    </id_info>
    <brief_title>EGCG for Hepatocellular Carcinoma Chemoprevention</brief_title>
    <acronym>CATCH-B</acronym>
    <official_title>Phase II Randomized Controlled Trial of Epigallocatechin Gallate for Hepatocellular Carcinoma Chemoprevention</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Texas Southwestern Medical Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Texas Southwestern Medical Center</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This phase II trial tests epigallocatechin gallate (EGCG) for its efficacy and safety in&#xD;
        preventing development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study will evaluate whether EGCG favorably modulate an HCC risk biomarker (PLSec) with&#xD;
        acceptable safety profile in patients with compensated cirrhosis and elevated HCC risk&#xD;
        determined by clinical variable-based score (FIB-4 index) and PLSec. Sixty participants will&#xD;
        be randomized (1:1) to either the study drub or placebo arm and receive the treatment for 24&#xD;
        weeks. The participants will orally take EGCG 600 mg capsules or placebo for the first 12&#xD;
        weeks. If an interim PLSec analysis at the end of week 8 is not improved without any&#xD;
        dose-limiting adverse events, the dose will be increased to 800 mg for the second 12 weeks.&#xD;
        If the interim PLSec is improved, 600 mg will be continued. After completing the 24-week&#xD;
        treatment, change in the PLSec test with the treatment is calculated by comparing pre- and&#xD;
        post-treatment serum samples in each patient, and the changes will be compared between the&#xD;
        treatment arms (primary endpoint). Complete adverse event profiles will be recorded, and&#xD;
        change in quality of life will be compared between the treatment arms (secondary endpoints).&#xD;
        If optional paired liver biopsy tissues are obtained, changes in tissue-based HCC risk&#xD;
        biomarker (PLS) and immunohistochemical markers of cell proliferation, neoplasm, senescence,&#xD;
        and fibrogenesis will be determined, changes in the FIB-4 index and liver stiffness&#xD;
        measurement will be determined, and association with incident HCC during the study period&#xD;
        will be evaluated (exploratory endpoints).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">August 31, 2028</completion_date>
    <primary_completion_date type="Anticipated">August 31, 2028</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Randomized placebo-controlled trial</intervention_model_description>
      <primary_purpose>Prevention</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>Double-blinded</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Change in Prognostic Liver Secretome signature (PLSec) score</measure>
      <time_frame>Baseline to week 24</time_frame>
      <description>HCC risk level at baseline and post-treatment will be determined as Prognostic Liver Secretome signature (PLSec) score, ranging from 0 (lowest risk) to 8 (highest risk).&#xD;
  Change in the biomarker-based HCC risk level will be calculated as delta-PLSec by subtracting the post-treatment PLSec score from the baseline pre-treatment PLSec score. delta-PLSec values will be compared between the EGCG and placebo arms using two-sample t-test.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Complete adverse event profile</measure>
      <time_frame>Baseline to week 24</time_frame>
      <description>Adverse events are monitored at least monthly and graded/recorded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5. The number and severity of adverse events will be tabulated and summarized across all grades. Grade 3+ adverse events will be similarly described and summarized separately.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in quality of life measured by the chronic liver disease questionnaire</measure>
      <time_frame>Baseline to week 24</time_frame>
      <description>Quality of life (QOL) will be measured by using the chronic liver disease questionnaire (CLDQ), which consists of 29 questions. Participants can select one answer from seven choices of descriptive answers for each question. Frequency distributions, graphical techniques and other descriptive measures will be used to summarize the results. When frequencies are compared, Fisher's exact test will be used.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Change in hepatic gene expression-based HCC risk biomarker, Prognostic Liver Signature (PLS) (optional)</measure>
      <time_frame>Baseline to week 24</time_frame>
      <description>When optional liver biopsy tissue is obtained, modulation of hepatic gene expression-based signature associated with HCC risk, Prognostic Liver Signature (PLS) is measured by comparing pre- and post-treatment liver biopsy samples. Change in HCC risk level will be quantified as combined enrichment score (CES) by comparing between the 2 time points. A positive and negative CES values indicate worsening and improvement of the PLS, respectively. Absolute value of the CES indicate magnitude of reduction (i.e., negative value) or increase (i.e., positive value) of HCC risk level. There is no defined range of CES. CES values are compared between the EGCG and placebo arms using two-sample t-test.</description>
    </other_outcome>
    <other_outcome>
      <measure>Change in positive signal intensities of immunohistochemistry markers (optional)</measure>
      <time_frame>Baseline to week 24</time_frame>
      <description>When optional liver biopsy tissue is obtained, change of immunohistochemical markers of cellular proliferation (Ki67), hepatic neoplasia (GST-p), cellular senescence (beta-gal), fibrogenesis (alpha-SMA) will be assessed using formalin-fixed pre-treatment paraffin-embedded (FFPE) tissues. Positivity for all of the markers will be quantified by higher intensity at pixel levels in captured images using the ImageJ software. The measurements are compared between the EGCG and placebo arms using one-sample t-test.</description>
    </other_outcome>
    <other_outcome>
      <measure>HCC incidence</measure>
      <time_frame>Average time frame of 1 year</time_frame>
      <description>The participants will be regularly followed every 6 months for HCC development for their life time. HCC diagnosis is based on the American Association for Study of Liver Disease (AASLD) clinical practice guidelines. Time to HCC development will be calculated as days between the treatment initiation data and date of HCC diagnosis. Cumulative HCC incidence will be compared between the treatment arms using log-rank test and Cox regression within and beyond the study period. This exploratory analysis will be performed through study completion with an anticipated average time frame of 1 year.</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>Cirrhosis, Liver</condition>
    <arm_group>
      <arm_group_label>Epigallocatechin gallate 600 - 800mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Epigallocatechin gallate (EGCG) 600mg will be administered daily via oral route for the initial 12 consecutive weeks on an outpatient basis. The dose of 600 mg will be continued for the second 12 weeks if an interim HCC biomarker test at the end of week 8 improves. If the interim test does not improve without dose-limiting adverse events, the dose will be increased to 800mg for the second 12 weeks, All participants will receive 24 weeks of treatment in total.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Oral administration of placebo for 24 weeks</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Epigallocatechin gallate (EGCG)</intervention_name>
      <description>EGCG is a green tea-derived catechin</description>
      <arm_group_label>Epigallocatechin gallate 600 - 800mg</arm_group_label>
      <other_name>Teavigo</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Placebo in the same capsule with the experimental agent (EGCG).</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Adults (≥ 18 years-old)&#xD;
  &#xD;
            -  Clinically and/or histologically diagnosed cirrhosis&#xD;
  &#xD;
            -  No active hepatic decompensation&#xD;
  &#xD;
            -  No prior history of HCC&#xD;
  &#xD;
            -  Adequate hematologic, hepatic, and renal function&#xD;
  &#xD;
            -  Karnofsky performance status score ≥70&#xD;
  &#xD;
            -  Both sexes and all racial/ethnic groups will be considered&#xD;
  &#xD;
            -  FIB-4 index &gt; 3.25&#xD;
  &#xD;
            -  High-risk PLSec at baseline&#xD;
  &#xD;
            -  Absence of HLA-B*35:01&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Prior or ongoing use of EGCG&#xD;
  &#xD;
            -  History of adverse reaction to green tea products&#xD;
  &#xD;
            -  Severe obesity (BMI &gt; 40 kg/m2)&#xD;
  &#xD;
            -  Active drinking&#xD;
  &#xD;
            -  EGCG treatment &lt;4 weeks or &lt;80% of planned regimen at the end of week 4&#xD;
  &#xD;
            -  HCC development during the study&#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>Yujin Hoshida, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>UT Southwestern</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Yujin Hoshida, MD, PhD</last_name>
      <phone>214-648-6137</phone>
      <email>yujin.hoshida@utsouthwestern.edu</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 9, 2023</study_first_submitted>
    <study_first_submitted_qc>August 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 29, 2023</study_first_posted>
    <last_update_submitted>August 27, 2023</last_update_submitted>
    <last_update_submitted_qc>August 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Texas Southwestern Medical Center</investigator_affiliation>
      <investigator_full_name>Yujin Hoshida, MD, PhD</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <keyword>hepatocellular carcinoma</keyword>
    <keyword>chemoprevention</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carcinoma</mesh_term>
      <mesh_term>Carcinoma, Hepatocellular</mesh_term>
      <mesh_term>Liver Cirrhosis</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>
  
  
text: 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/NCT06015022
  org study id: STU-2023-0233
  nct id: NCT06015022
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  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.
  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).
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Randomized placebo-controlled trial
  primary purpose: Prevention
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: Double-blinded
  measure: Change in Prognostic Liver Secretome signature (PLSec) score
  time frame: Baseline to week 24
  description: HCC risk level at baseline and post-treatment will be determined as Prognostic Liver Secretome signature (PLSec) score, ranging from 0 (lowest risk) to 8 (highest risk).
  Change in the biomarker-based HCC risk level will be calculated as delta-PLSec by subtracting the post-treatment PLSec score from the baseline pre-treatment PLSec score. delta-PLSec values will be compared between the EGCG and placebo arms using two-sample t-test.
  measure: Complete adverse event profile
  time frame: Baseline to week 24
  description: Adverse events are monitored at least monthly and graded/recorded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5. The number and severity of adverse events will be tabulated and summarized across all grades. Grade 3+ adverse events will be similarly described and summarized separately.
  measure: Change in quality of life measured by the chronic liver disease questionnaire
  time frame: Baseline to week 24
  description: Quality of life (QOL) will be measured by using the chronic liver disease questionnaire (CLDQ), which consists of 29 questions. Participants can select one answer from seven choices of descriptive answers for each question. Frequency distributions, graphical techniques and other descriptive measures will be used to summarize the results. When frequencies are compared, Fisher's exact test will be used.
  measure: Change in hepatic gene expression-based HCC risk biomarker, Prognostic Liver Signature (PLS) (optional)
  time frame: Baseline to week 24
  description: When optional liver biopsy tissue is obtained, modulation of hepatic gene expression-based signature associated with HCC risk, Prognostic Liver Signature (PLS) is measured by comparing pre- and post-treatment liver biopsy samples. Change in HCC risk level will be quantified as combined enrichment score (CES) by comparing between the 2 time points. A positive and negative CES values indicate worsening and improvement of the PLS, respectively. Absolute value of the CES indicate magnitude of reduction (i.e., negative value) or increase (i.e., positive value) of HCC risk level. There is no defined range of CES. CES values are compared between the EGCG and placebo arms using two-sample t-test.
  measure: Change in positive signal intensities of immunohistochemistry markers (optional)
  time frame: Baseline to week 24
  description: When optional liver biopsy tissue is obtained, change of immunohistochemical markers of cellular proliferation (Ki67), hepatic neoplasia (GST-p), cellular senescence (beta-gal), fibrogenesis (alpha-SMA) will be assessed using formalin-fixed pre-treatment paraffin-embedded (FFPE) tissues. Positivity for all of the markers will be quantified by higher intensity at pixel levels in captured images using the ImageJ software. The measurements are compared between the EGCG and placebo arms using one-sample t-test.
  measure: HCC incidence
  time frame: Average time frame of 1 year
  description: The participants will be regularly followed every 6 months for HCC development for their life time. HCC diagnosis is based on the American Association for Study of Liver Disease (AASLD) clinical practice guidelines. Time to HCC development will be calculated as days between the treatment initiation data and date of HCC diagnosis. Cumulative HCC incidence will be compared between the treatment arms using log-rank test and Cox regression within and beyond the study period. This exploratory analysis will be performed through study completion with an anticipated average time frame of 1 year.
  arm group label: Epigallocatechin gallate 600 - 800mg
  arm group type: Experimental
  description: Epigallocatechin gallate (EGCG) 600mg will be administered daily via oral route for the initial 12 consecutive weeks on an outpatient basis. The dose of 600 mg will be continued for the second 12 weeks if an interim HCC biomarker test at the end of week 8 improves. If the interim test does not improve without dose-limiting adverse events, the dose will be increased to 800mg for the second 12 weeks, All participants will receive 24 weeks of treatment in total.
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Oral administration of placebo for 24 weeks
  intervention type: Drug
  intervention name: Epigallocatechin gallate (EGCG)
  description: EGCG is a green tea-derived catechin
  arm group label: Epigallocatechin gallate 600 - 800mg
  other name: Teavigo
  intervention type: Other
  intervention name: Placebo
  description: Placebo in the same capsule with the experimental agent (EGCG).
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Yujin Hoshida, MD, PhD
  role: Principal Investigator
  affiliation: UT Southwestern
  last name: Yujin Hoshida, MD, PhD
  phone: 214-648-6137
  email: yujin.hoshida@utsouthwestern.edu
  responsible party type: Principal Investigator
  investigator affiliation: University of Texas Southwestern Medical Center
  investigator full name: Yujin Hoshida, MD, PhD
  investigator title: Professor
  mesh term: Carcinoma
  mesh term: Carcinoma, Hepatocellular
  mesh term: Liver Cirrhosis
  mesh term: Epigallocatechin gallate