<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/NCT04499833</url>
  </required_header>
  <id_info>
    <org_study_id>CHULC.CI.HCC.2020</org_study_id>
    <nct_id>NCT04499833</nct_id>
  </id_info>
  <brief_title>HepatoPredict Prognostic Tool for the Decision of Liver Transplant in Hepatocellular Carcinoma</brief_title>
  <acronym>HepatoPredict</acronym>
  <official_title>Evaluation of the HepatoPredict Prognostic Tool in the Decision of Liver Transplant in Hepatocellular Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centro Hospitalar de Lisboa Central</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ophiomics - Precision Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Centro Hospitalar de Lisboa Central</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>
      Liver transplant is the most effective treatment for hepatocellular carcinoma (HCC) in&#xD;
      cirrhosis. Due to organs shortage, the proper selection of patients is imperative. Prevailing&#xD;
      clinical morphological models used in most centres (Milan Criteria), can exclude potential&#xD;
      candidates and include patients with aggressive biological behaviour. To more accurately&#xD;
      select candidates for liver transplant, the inclusion of criteria that could predict the&#xD;
      behaviour and aggressiveness of tumours, such as molecular markers, might be useful.&#xD;
&#xD;
      The investigators propose the use of a new algorithm (HepatoPredict Prognostic Tool), that&#xD;
      combine clinical and molecular criteria that address the biology of tumours, in a single&#xD;
      centre prospective, intervention study. Data from the &quot;HepatoPredict genomic signature&quot; are&#xD;
      added to the clinical and imagiology algorithm. Based on this tool, patients outside the&#xD;
      usual eligibility criteria for liver transplant will be proposed for this treatment. These&#xD;
      patients will be transplanted with marginal livers or with livers from patients with Familial&#xD;
      Amyloid Polyneuropathy, not competing with patients on the waiting list. Patients will be&#xD;
      followed up to 60 months after transplant, to assess survival and HCC recurrence with&#xD;
      biannual imagiology screening. Survival and disease-free-survival rates will be compared with&#xD;
      those obtained by the usual management of patients included and excluded by Milan Criteria.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Liver transplant is the most effective treatment for hepatocellular carcinoma (HCC) in&#xD;
      cirrhosis. Due to organs shortage, the proper selection of patients is imperative. Prevailing&#xD;
      clinical morphological models used in most centres (Milan Criteria), can exclude potential&#xD;
      candidates and include patients with aggressive biological behaviour. To more accurately&#xD;
      select candidates for liver transplant, the inclusion of criteria that could predict the&#xD;
      behaviour and aggressiveness of tumours, such as molecular markers, might be useful. The&#xD;
      investigators propose the use of a new algorithm (HepatoPredict Prognostic Tool, Ophiomics),&#xD;
      combining morphologic information, clinical and molecular criteria, in a prospective,&#xD;
      intervention, single centre study.&#xD;
&#xD;
      Patients aged 18 to 70 years, with HCC in cirrhosis, not eligible for liver transplant under&#xD;
      the &quot;Milan Criteria&quot;, whom had the following morphologic characteristics: total tumour volume&#xD;
      below 500 cm3, total number of tumour lesions below 10 and maximum individual tumour diameter&#xD;
      below 10 cm, will be proposed for the &quot;HepatoPredict genomic signature&quot; analysis (Ophiomics),&#xD;
      obtained from DNA of tumor samples. Those considered candidates by the algorithm are to be&#xD;
      proposed for transplant with marginal livers or with livers from patients with Familial&#xD;
      Amyloid Polyneuropathy.&#xD;
&#xD;
      Patients will be followed up to 60 months after transplant, to assess survival and HCC&#xD;
      recurrence with biannual imagiology screening by triphasic CT scan. Additionally, circulating&#xD;
      tumour DNA will be assessed previously to the transplant and biannually for up to 60 months.&#xD;
      Survival and disease-free-survival rates will be compared with those obtained with the usual&#xD;
      management of patients included and excluded by Milan Criteria, both in the same referral&#xD;
      transplant center and in the published literature.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 25, 2021</start_date>
  <completion_date type="Anticipated">December 31, 2029</completion_date>
  <primary_completion_date type="Anticipated">October 30, 2028</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>Prospective evaluation of patients with hepatocellular carcinoma in cirrhotic liver, outside the &quot;Milan Criteria&quot; for liver transplant, that comply with the morphologic criteria stablished for the proposed HepatoPredict Tool: (1) Total tumour volume below 500 cm3; (2) Total number of tumour lesions below 10; and (3) maximum individual tumour diameter below 10 cm. Those patients are proposed to be submitted to molecular study of the hepatocellular carcinoma and, if comply with the &quot;HepatoPredict genomic signature&quot;, liver transplantation will be proposed. Patients will be followed up for up to 5 years after transplantation for survival and survival-free-of-disease.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>death</measure>
    <time_frame>from 6 months after liver transplant up to 60 months</time_frame>
    <description>death by any cause</description>
  </primary_outcome>
  <primary_outcome>
    <measure>hepatocellular carcinoma recurrence</measure>
    <time_frame>from 6 months after liver transplant up to 60 months</time_frame>
    <description>identification of hepatocellular carcinoma recurrence through biannual triphasic CT scan</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>hepatocellular carcinoma recurrence through liquid biopsy</measure>
    <time_frame>from 6 months after liver transplant up to 60 months</time_frame>
    <description>early identification of hepatocellular carcinoma DNA through biannual serum samples (liquid biopsy)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Hepatocellular Carcinoma, Scirrhous</condition>
  <condition>Recurrence Tumor</condition>
  <arm_group>
    <arm_group_label>liver transplant outside the &quot;Milan Criteria&quot;</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patients with hepatocellular carcinoma, outside the &quot;Milan Criteria&quot;, that complied with the proposed HepatoPredictTool, submitted to liver transplant</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>liver transplant</intervention_name>
    <description>liver transplant</description>
    <arm_group_label>liver transplant outside the &quot;Milan Criteria&quot;</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Hepatocellular carcinoma associated with cirrhosis&#xD;
&#xD;
          -  Ages between 18 and 70 years&#xD;
&#xD;
          -  Total tumour volume below 500 cm3&#xD;
&#xD;
          -  Total number of tumour lesions below 10&#xD;
&#xD;
          -  Maximum individual tumour diameter below 10 cm&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  eligible under the &quot;Milan Criteria&quot;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hugo Pinto-Marques, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centro Hospitalar Universitário de Lisboa Central</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hugo Pinto-Marques, MD PhD</last_name>
    <phone>+351917302214</phone>
    <email>hugo.marques3@chlc.min-saude.pt</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sílvia Gomes-da-Silva, MD</last_name>
    <phone>+351916876393</phone>
    <email>silvia.silva@chlc.min-saude.pt</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Centro Hepato-bilio-pancreático e de Transplantação do Hospital Curry Cabral</name>
      <address>
        <city>Lisboa</city>
        <zip>1069-166</zip>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hugo Pinto-Marques, MD PhD</last_name>
      <phone>+351917302214</phone>
      <email>hugo.marques3@chlc.min-saude.pt</email>
    </contact>
    <contact_backup>
      <last_name>Luis Pereira-de-Silva, MD PhD</last_name>
      <phone>+351213596402</phone>
      <phone_ext>51402</phone_ext>
      <email>centro.investigacao@chlc.min-saude.pt</email>
    </contact_backup>
    <investigator>
      <last_name>Sílvia Gomes-da-Silva, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jose Pereira-Leal, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Portugal</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>July 31, 2020</study_first_submitted>
  <study_first_submitted_qc>July 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>June 3, 2022</last_update_submitted>
  <last_update_submitted_qc>June 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>cirrhosis</keyword>
  <keyword>Hepatocellular Carcinoma</keyword>
  <keyword>liver transplant</keyword>
  <keyword>tumor recurrence</keyword>
  <keyword>biomarkers</keyword>
  <keyword>prognosis</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>Adenocarcinoma, Scirrhous</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04499833
org study id: CHULC.CI.HCC.2020
nct id: NCT04499833
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Liver transplant is the most effective treatment for hepatocellular carcinoma (HCC) in
      cirrhosis. Due to organs shortage, the proper selection of patients is imperative. Prevailing
      clinical morphological models used in most centres (Milan Criteria), can exclude potential
      candidates and include patients with aggressive biological behaviour. To more accurately
      select candidates for liver transplant, the inclusion of criteria that could predict the
      behaviour and aggressiveness of tumours, such as molecular markers, might be useful.

      The investigators propose the use of a new algorithm (HepatoPredict Prognostic Tool), that
      combine clinical and molecular criteria that address the biology of tumours, in a single
      centre prospective, intervention study. Data from the "HepatoPredict genomic signature" are
      added to the clinical and imagiology algorithm. Based on this tool, patients outside the
      usual eligibility criteria for liver transplant will be proposed for this treatment. These
      patients will be transplanted with marginal livers or with livers from patients with Familial
      Amyloid Polyneuropathy, not competing with patients on the waiting list. Patients will be
      followed up to 60 months after transplant, to assess survival and HCC recurrence with
      biannual imagiology screening. Survival and disease-free-survival rates will be compared with
      those obtained by the usual management of patients included and excluded by Milan Criteria.
Liver transplant is the most effective treatment for hepatocellular carcinoma (HCC) in
      cirrhosis. Due to organs shortage, the proper selection of patients is imperative. Prevailing
      clinical morphological models used in most centres (Milan Criteria), can exclude potential
      candidates and include patients with aggressive biological behaviour. To more accurately
      select candidates for liver transplant, the inclusion of criteria that could predict the
      behaviour and aggressiveness of tumours, such as molecular markers, might be useful. The
      investigators propose the use of a new algorithm (HepatoPredict Prognostic Tool, Ophiomics),
      combining morphologic information, clinical and molecular criteria, in a prospective,
      intervention, single centre study.

      Patients aged 18 to 70 years, with HCC in cirrhosis, not eligible for liver transplant under
      the "Milan Criteria", whom had the following morphologic characteristics: total tumour volume
      below 500 cm3, total number of tumour lesions below 10 and maximum individual tumour diameter
      below 10 cm, will be proposed for the "HepatoPredict genomic signature" analysis (Ophiomics),
      obtained from DNA of tumor samples. Those considered candidates by the algorithm are to be
      proposed for transplant with marginal livers or with livers from patients with Familial
      Amyloid Polyneuropathy.

      Patients will be followed up to 60 months after transplant, to assess survival and HCC
      recurrence with biannual imagiology screening by triphasic CT scan. Additionally, circulating
      tumour DNA will be assessed previously to the transplant and biannually for up to 60 months.
      Survival and disease-free-survival rates will be compared with those obtained with the usual
      management of patients included and excluded by Milan Criteria, both in the same referral
      transplant center and in the published literature.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Prospective evaluation of patients with hepatocellular carcinoma in cirrhotic liver, outside the "Milan Criteria" for liver transplant, that comply with the morphologic criteria stablished for the proposed HepatoPredict Tool: (1) Total tumour volume below 500 cm3; (2) Total number of tumour lesions below 10; and (3) maximum individual tumour diameter below 10 cm. Those patients are proposed to be submitted to molecular study of the hepatocellular carcinoma and, if comply with the "HepatoPredict genomic signature", liver transplantation will be proposed. Patients will be followed up for up to 5 years after transplantation for survival and survival-free-of-disease.
primary purpose: Treatment
masking: None (Open Label)
measure: death
time frame: from 6 months after liver transplant up to 60 months
description: death by any cause
measure: hepatocellular carcinoma recurrence
time frame: from 6 months after liver transplant up to 60 months
description: identification of hepatocellular carcinoma recurrence through biannual triphasic CT scan
measure: hepatocellular carcinoma recurrence through liquid biopsy
time frame: from 6 months after liver transplant up to 60 months
description: early identification of hepatocellular carcinoma DNA through biannual serum samples (liquid biopsy)
arm group label: liver transplant outside the "Milan Criteria"
arm group type: Experimental
description: patients with hepatocellular carcinoma, outside the "Milan Criteria", that complied with the proposed HepatoPredictTool, submitted to liver transplant
intervention type: Procedure
intervention name: liver transplant
description: liver transplant
arm group label: liver transplant outside the "Milan Criteria"
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Hugo Pinto-Marques, MD PhD
role: Principal Investigator
affiliation: Centro Hospitalar Universitário de Lisboa Central
last name: Hugo Pinto-Marques, MD PhD
phone: +351917302214
email: hugo.marques3@chlc.min-saude.pt
last name: Sílvia Gomes-da-Silva, MD
phone: +351916876393
email: silvia.silva@chlc.min-saude.pt
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: Portugal
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Adenocarcinoma, Scirrhous
mesh term: Recurrence
sharing ipd: No