<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/NCT01673607</url>
  </required_header>
  <id_info>
    <org_study_id>METAHEP</org_study_id>
    <nct_id>NCT01673607</nct_id>
  </id_info>
  <brief_title>Study of Immune Response and Liver Damage Induced by Chemotherapy for Liver Metastases of Colorectal Cancer</brief_title>
  <acronym>METAHEP</acronym>
  <sponsors>
    <lead_sponsor>
      <agency>Poitiers University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Poitiers University Hospital</source>
  <brief_summary>
    <textblock>
      The immune response at primary tumor has a major role in the prognosis of colorectal cancer&#xD;
      (CRC). Some studies suggest a prognosis value of cytotoxic T cell and memory T cells at&#xD;
      primary tumor greater than tumoral stage. There is no work in the literature that has&#xD;
      examined the prognosis value of the immune response in liver metastases. To study immune&#xD;
      cells (histology) and inflammatory response (cytokines) in liver metastases is a challenge to&#xD;
      understand the effectiveness of chemotherapy used in this situation.&#xD;
&#xD;
      The chemotherapy used in liver metastases of colorectal cancer also have effects on&#xD;
      non-tumoral liver tumor and therefore can interfere with postoperative complications of&#xD;
      hepatic resection. Sinusoidal dilatation is present in 20% to 80% of patients who received&#xD;
      oxaliplatin before hepatectomy. Steatosis is frequently observed after administration of 5-FU&#xD;
      alone or in combination with irinotecan. This steatosis may also be accompanied by&#xD;
      inflammatory lesions (steatohepatitis), especially after administration of oxaliplatin or&#xD;
      irinotecan and is associated with increased postoperative mortality. The hepatic toxicity of&#xD;
      new biological agents is not well known (cetuximab and bevacizumab). The mechanisms of&#xD;
      chemotherapy-induced toxicities are currently unknown. The main objective is to analyze the&#xD;
      profile of the immune response in liver metastases of CRC and find the link with the&#xD;
      radiological response. Measurements will be made by quantitative RT-PCR on frozen liver&#xD;
      biopsies. Secondary objective is to seek a correlation between the histological lesions&#xD;
      induced by chemotherapy and non-invasive tests for liver fibrosis. The secondary endpoints&#xD;
      are rate of immune cells, histologic response (percentage of tumor necrosis), disease-free&#xD;
      survival, the non-invasive test of fibrosis, the chemotherapy-induced liver injury, cytokines&#xD;
      and circulating angiogenic factors.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 11, 2012</start_date>
  <completion_date type="Anticipated">March 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
  </study_design_info>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Resectable Hepatic Metastases of Colorectal Cancer</condition>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Biopsie liver</intervention_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patient older than 18 years.&#xD;
&#xD;
          -  Patients with histologically proven colorectal cancer with resectable or potentially&#xD;
             resectable liver metastases.&#xD;
&#xD;
          -  First line chemotherapy alone or combination with intravenous 5FU, oral 5FU&#xD;
             (capecitabine), oxaliplatin, irinotecan, cetuximab, panitumumab or bevacizumab&#xD;
             (LV5FU2, XELODA, FOLFIRI, FOLFOX, XELOX, XELIRI alone or in combination with either&#xD;
             cetuximab or panitumumab or bevacizumab).&#xD;
&#xD;
          -  Signature of informed consent.&#xD;
&#xD;
          -  Patient affiliated to French Social Security.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients taking immunosuppressive therapy.&#xD;
&#xD;
          -  Lack of measurable tumoral target.&#xD;
&#xD;
          -  Patients with a contre-indication of all chemotherapy used: oxaliplatin, irinotecan,&#xD;
             fluorouracil, capecitabine, cetuximab, panitumumab, bevacizumab.&#xD;
&#xD;
          -  Patients hospitalized without consent.&#xD;
&#xD;
          -  Patients in emergency situations.&#xD;
&#xD;
          -  Patients under guardianship.&#xD;
&#xD;
          -  Patients deprived of their liberty by judicial or administrative procedure.&#xD;
&#xD;
          -  Pregnant or nursing women, women without effective contraception.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>David TOUGERON, MD</last_name>
    <phone>33.5.49.44.37.51</phone>
    <email>david.tougeron@chu-poitiers.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Poitiers University Hospital</name>
      <address>
        <city>Poitiers</city>
        <zip>86021</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David TOUGERON, MD</last_name>
      <phone>33.5.49.44.37.51</phone>
      <email>david.tougeron@chu-poitiers.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>February 13, 2012</study_first_submitted>
  <study_first_submitted_qc>August 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2012</study_first_posted>
  <last_update_submitted>September 28, 2021</last_update_submitted>
  <last_update_submitted_qc>September 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 29, 2021</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>Colorectal Neoplasms</mesh_term>
    <mesh_term>Neoplasm Metastasis</mesh_term>
  </condition_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/NCT01673607
org study id: METAHEP
nct id: NCT01673607
lead sponsor: 
The immune response at primary tumor has a major role in the prognosis of colorectal cancer
      (CRC). Some studies suggest a prognosis value of cytotoxic T cell and memory T cells at
      primary tumor greater than tumoral stage. There is no work in the literature that has
      examined the prognosis value of the immune response in liver metastases. To study immune
      cells (histology) and inflammatory response (cytokines) in liver metastases is a challenge to
      understand the effectiveness of chemotherapy used in this situation.

      The chemotherapy used in liver metastases of colorectal cancer also have effects on
      non-tumoral liver tumor and therefore can interfere with postoperative complications of
      hepatic resection. Sinusoidal dilatation is present in 20% to 80% of patients who received
      oxaliplatin before hepatectomy. Steatosis is frequently observed after administration of 5-FU
      alone or in combination with irinotecan. This steatosis may also be accompanied by
      inflammatory lesions (steatohepatitis), especially after administration of oxaliplatin or
      irinotecan and is associated with increased postoperative mortality. The hepatic toxicity of
      new biological agents is not well known (cetuximab and bevacizumab). The mechanisms of
      chemotherapy-induced toxicities are currently unknown. The main objective is to analyze the
      profile of the immune response in liver metastases of CRC and find the link with the
      radiological response. Measurements will be made by quantitative RT-PCR on frozen liver
      biopsies. Secondary objective is to seek a correlation between the histological lesions
      induced by chemotherapy and non-invasive tests for liver fibrosis. The secondary endpoints
      are rate of immune cells, histologic response (percentage of tumor necrosis), disease-free
      survival, the non-invasive test of fibrosis, the chemotherapy-induced liver injury, cytokines
      and circulating angiogenic factors.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
intervention type: Procedure
intervention name: Biopsie liver
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: David TOUGERON, MD
phone: 33.5.49.44.37.51
email: david.tougeron@chu-poitiers.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Neoplasm Metastasis