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/NCT05990959</url>
    </required_header>
    <id_info>
      <org_study_id>CMUH111-REC2-039</org_study_id>
      <nct_id>NCT05990959</nct_id>
    </id_info>
    <brief_title>Risk Factors, Prognosis, and Potential Chemoprevention Drugs in Patients With Recurrent Hepatocellular Carcinoma After Curative Surgeries: a Nationwide Retrospective Cohort Study and a Multi-center Prospective Cohort Analysis</brief_title>
    <official_title>Risk Factors, Prognosis, and Potential Chemoprevention Drugs in Patients With Recurrent Hepatocellular Carcinoma After Curative Surgeries: a Nationwide Retrospective Cohort Study and a Multi-center Prospective Cohort Analysis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>China Medical University Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Ministry of Health and Welfare, Taiwan</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>China Medical University Hospital</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Backgrounds: Surgeries are the mainstream of curative therapies for hepatocellular carcinoma&#xD;
        (HCC). However, high risk of recurrent HCC after liver surgeries is still the unsolved&#xD;
        clinical issue (early recurrence 21% per year; late recurrence 18% per year). Early&#xD;
        recurrence mainly result from disseminated HCC; by contrast, late recurrence usually&#xD;
        originate from carcinogenic microenvironment. Currently, no large-scale nationwide studies&#xD;
        that integrate laboratory date and clinical information was performed to investigate risk&#xD;
        factors and prognosis of post-operative recurrent HCC. Besides, owing to economic issue, few&#xD;
        companies would initiate pharmacologic studies to investigate chemoprevention agents for HCC.&#xD;
        Furthermore, few biomarkers were discovered from Taiwanese HCC cohort to predict&#xD;
        post-operative tumor recurrence because of no standardized cooperative platforms to share&#xD;
        biological tissue and clinical information. Therefore, we wish to utilize a nationwide&#xD;
        retrospective cohort from integrated national health insurance database (NHIRD) and a&#xD;
        prospective multi-center clinical cohort study to address aforementioned issues.&#xD;
  &#xD;
        Aims:&#xD;
  &#xD;
          1. Investigate risk factors and prognosis of post-operative recurrent HCC in Taiwanese&#xD;
             cohort&#xD;
  &#xD;
          2. Discover chemoprevention targets from generic drugs to reduce risk of post-operative&#xD;
             recurrent HCC&#xD;
  &#xD;
          3. Determine biomarkers from Taiwanese cohort in prediction of post-operative recurrent HCC&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Study subject and methods:&#xD;
  &#xD;
        Nationwide retrospective cohort study&#xD;
  &#xD;
          1. Establish prediction models for postoperative recurrent HCC by analyzing surgical HCC&#xD;
             patients' clinical information and perioperative laboratory date based on the database&#xD;
             of a nationwide retrospective cohort organized by the Ministry of Health and Welfare and&#xD;
             Health insurance office&#xD;
  &#xD;
          2. Discover chemoprevention agents in association with reduced risk of post-operative&#xD;
             recurrent HCC using the aforementioned database&#xD;
  &#xD;
        Multicenter prospective cohort study:&#xD;
  &#xD;
          1. To discover biomarkers in prediction of post-operative recurrent HCC , we will establish&#xD;
             a shared platform to prospectively and systemically collect Taiwanese HCC surgical&#xD;
             patients' bio-materials and clinical information from China Medical University Hospital,&#xD;
             Asian University Hospital, Mackay Hospital, Taichung Veterans General Hospital, E-Da&#xD;
             Hospital,…etc.&#xD;
  &#xD;
          2. Using the multicenter prospective cohort, we could validate the results from the&#xD;
             nationwide retrospective cohort study, and even improve the prediction models by adding&#xD;
             biological parameters that are not available in the nationwide retrospective cohort&#xD;
  &#xD;
        Hospital biobank based retrospective case-control study Investigate clinical and biological&#xD;
        parameters in prediction of tumor recurrence in HCC surgical patients by hospital based&#xD;
        biobank and relevant clinical information&#xD;
  &#xD;
        Laboratory in-vivo and in-vitro study Investigate causal relationship between prognosis of&#xD;
        HCC and selected biomarkers from above studies as well as four universal tumor theragnostic&#xD;
        markers (ADAM9, MTHFD2, RRM2, and SLC2A1) and explore treatment effects of corresponding&#xD;
        inhibitors&#xD;
  &#xD;
        Expected results: For scientists, they may benefit from the shared database of Taiwanese HCC&#xD;
        surgical patients for the HCC related researches; for physicians, they could predict risk of&#xD;
        post-operative recurrent HCC in Taiwanese HCC patients and use generic drugs as potentially&#xD;
        chemopreventive drugs for HCC; for patients, they could benefit from the personalized medical&#xD;
        advice to increase the survival; for the authorities, they could design a policy to reduce&#xD;
        the risk of post-operative recurrent HCC, and even prolong HCC patients' survival in a&#xD;
        cost-effective way by using generic drugs as chemopreventive regimens for HCC.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">April 22, 2022</start_date>
    <completion_date type="Anticipated">December 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 2025</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Retrospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Overall survival</measure>
      <time_frame>5 year</time_frame>
      <description>Overall survival</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Disease free survival</measure>
      <time_frame>5 year</time_frame>
      <description>Disease free survival</description>
    </primary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">800</enrollment>
    <condition>Hepatocellular Carcinoma Recurrent</condition>
    <condition>Surgery</condition>
    <arm_group>
      <arm_group_label>HCC_surg</arm_group_label>
      <description>HCC surgical patients who would receive surgical interventions based on clinical judgment and would donate biospecimen for research after signing informed consent permission.</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>No intervention for research purpose</intervention_name>
      <description>No any intervention will be applied under research purpose. All procedure or drugs would be given to the patient under best clinical judgment, not for research purpose.</description>
      <arm_group_label>HCC_surg</arm_group_label>
    </intervention>
    <biospec_retention>Samples With DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Biospecimen would be retrieved from already stored biobank in our own affiliation .The&#xD;
        biospecimen may contain blood and liver tumors.&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          All HCC surgical patients aged more than 20 year-old who sign informed consent for donating&#xD;
          remnant tissue or blood after liver surgeries that would be performed under best clinical&#xD;
          judgment, NOT for research purpose.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  All HCC surgical patients aged more than 20 year-old who sign informed consent for&#xD;
               donating remnant tissue or blood after liver surgeries&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pregnant women&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>20 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Chun-Chieh Yeh, Dr.</last_name>
      <role>Principal Investigator</role>
      <affiliation>China Medical University Hospital,Taiwan</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Chun-Chieh Yeh, Dr.</last_name>
      <phone>886975681449</phone>
      <email>Transplantyeh@gmail.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>China Medical University Hospital, Department of Surgery</name>
        <address>
          <city>Taichung</city>
          <zip>404</zip>
          <country>Taiwan</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Chun-Chieh Yeh, Dr.</last_name>
        <phone>+886-975681449</phone>
        <email>Transplantyeh@gmail.com</email>
      </contact>
    </location>
    <location_countries>
      <country>Taiwan</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 5, 2023</study_first_submitted>
    <study_first_submitted_qc>August 5, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 5, 2023</last_update_submitted>
    <last_update_submitted_qc>August 5, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>China Medical University Hospital</investigator_affiliation>
      <investigator_full_name>Chun Chieh Yeh</investigator_full_name>
      <investigator_title>Dr.</investigator_title>
    </responsible_party>
    <keyword>hepatocellular carcinoma</keyword>
    <keyword>Recurrent</keyword>
    <keyword>Surgery</keyword>
    <keyword>Chemoprevention</keyword>
    <keyword>National Health Insurance Research Database</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>Recurrence</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>All patient's privacy would be protected under our IRB regulation. Thus, I cannot release IPD.</ipd_description>
    </patient_data>
    <!-- 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/NCT05990959
  org study id: CMUH111-REC2-039
  nct id: NCT05990959
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Backgrounds: Surgeries are the mainstream of curative therapies for hepatocellular carcinoma
        (HCC). However, high risk of recurrent HCC after liver surgeries is still the unsolved
        clinical issue (early recurrence 21% per year; late recurrence 18% per year). Early
        recurrence mainly result from disseminated HCC; by contrast, late recurrence usually
        originate from carcinogenic microenvironment. Currently, no large-scale nationwide studies
        that integrate laboratory date and clinical information was performed to investigate risk
        factors and prognosis of post-operative recurrent HCC. Besides, owing to economic issue, few
        companies would initiate pharmacologic studies to investigate chemoprevention agents for HCC.
        Furthermore, few biomarkers were discovered from Taiwanese HCC cohort to predict
        post-operative tumor recurrence because of no standardized cooperative platforms to share
        biological tissue and clinical information. Therefore, we wish to utilize a nationwide
        retrospective cohort from integrated national health insurance database (NHIRD) and a
        prospective multi-center clinical cohort study to address aforementioned issues.
  
        Aims:
  
          1. Investigate risk factors and prognosis of post-operative recurrent HCC in Taiwanese
             cohort
  
          2. Discover chemoprevention targets from generic drugs to reduce risk of post-operative
             recurrent HCC
  
          3. Determine biomarkers from Taiwanese cohort in prediction of post-operative recurrent HCC
  Study subject and methods:
  
        Nationwide retrospective cohort study
  
          1. Establish prediction models for postoperative recurrent HCC by analyzing surgical HCC
             patients' clinical information and perioperative laboratory date based on the database
             of a nationwide retrospective cohort organized by the Ministry of Health and Welfare and
             Health insurance office
  
          2. Discover chemoprevention agents in association with reduced risk of post-operative
             recurrent HCC using the aforementioned database
  
        Multicenter prospective cohort study:
  
          1. To discover biomarkers in prediction of post-operative recurrent HCC , we will establish
             a shared platform to prospectively and systemically collect Taiwanese HCC surgical
             patients' bio-materials and clinical information from China Medical University Hospital,
             Asian University Hospital, Mackay Hospital, Taichung Veterans General Hospital, E-Da
             Hospital,…etc.
  
          2. Using the multicenter prospective cohort, we could validate the results from the
             nationwide retrospective cohort study, and even improve the prediction models by adding
             biological parameters that are not available in the nationwide retrospective cohort
  
        Hospital biobank based retrospective case-control study Investigate clinical and biological
        parameters in prediction of tumor recurrence in HCC surgical patients by hospital based
        biobank and relevant clinical information
  
        Laboratory in-vivo and in-vitro study Investigate causal relationship between prognosis of
        HCC and selected biomarkers from above studies as well as four universal tumor theragnostic
        markers (ADAM9, MTHFD2, RRM2, and SLC2A1) and explore treatment effects of corresponding
        inhibitors
  
        Expected results: For scientists, they may benefit from the shared database of Taiwanese HCC
        surgical patients for the HCC related researches; for physicians, they could predict risk of
        post-operative recurrent HCC in Taiwanese HCC patients and use generic drugs as potentially
        chemopreventive drugs for HCC; for patients, they could benefit from the personalized medical
        advice to increase the survival; for the authorities, they could design a policy to reduce
        the risk of post-operative recurrent HCC, and even prolong HCC patients' survival in a
        cost-effective way by using generic drugs as chemopreventive regimens for HCC.
  observational model: Cohort
  time perspective: Retrospective
  measure: Overall survival
  time frame: 5 year
  description: Overall survival
  measure: Disease free survival
  time frame: 5 year
  description: Disease free survival
  arm group label: HCC_surg
  description: HCC surgical patients who would receive surgical interventions based on clinical judgment and would donate biospecimen for research after signing informed consent permission.
  intervention type: Other
  intervention name: No intervention for research purpose
  description: No any intervention will be applied under research purpose. All procedure or drugs would be given to the patient under best clinical judgment, not for research purpose.
  arm group label: HCC_surg
  Biospecimen would be retrieved from already stored biobank in our own affiliation .The
        biospecimen may contain blood and liver tumors.
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 20 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Chun-Chieh Yeh, Dr.
  role: Principal Investigator
  affiliation: China Medical University Hospital,Taiwan
  last name: Chun-Chieh Yeh, Dr.
  phone: 886975681449
  email: Transplantyeh@gmail.com
  facility: 
  status: Recruiting
  contact: 
  country: Taiwan
  responsible party type: Principal Investigator
  investigator affiliation: China Medical University Hospital
  investigator full name: Chun Chieh Yeh
  investigator title: Dr.
  mesh term: Carcinoma
  mesh term: Carcinoma, Hepatocellular
  mesh term: Recurrence
  sharing ipd: No
  ipd description: All patient's privacy would be protected under our IRB regulation. Thus, I cannot release IPD.