<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/NCT02232932</url>
  </required_header>
  <id_info>
    <org_study_id>P120106</org_study_id>
    <nct_id>NCT02232932</nct_id>
  </id_info>
  <brief_title>Liver Resection Versus Radio-chemotherapy-Transplantation for Hilar Cholangiocarcinoma</brief_title>
  <acronym>TRANSPHIL</acronym>
  <official_title>Randomized Prospective Multicentric Study: Radio-chemotherapy and Liver Transplantation Versus Liver Resection to Treat Respectable Hilar Cholangiocarcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A prospective, open-label, randomised, multicentre, comparative study in two parallel groups&#xD;
      comparing an interventional group with liver transplantation preceded by neoadjuvant&#xD;
      radio-chemotherapy and a control group receiving conventional liver and bile duct resection.&#xD;
&#xD;
      The primary endpoint will be overall survival at 5 years in the intent-to-treat population.&#xD;
      The secondary endpoint will be recurrence-free survival at 3 years evaluated by CT-scan and&#xD;
      tumoral markers (Carcinoembryonic antigen (CAE) and cancer antigen (CA19.9)) in the&#xD;
      intent-to-treat population.&#xD;
&#xD;
      The number of subjects necessary is 54 patients (27 x 2): this population will enable the&#xD;
      demonstration of a significant difference is 5-year survival rates between the transplanted&#xD;
      group and the resected group with a power of 80% and a first-species risk of 5%, under the&#xD;
      hypothesis that these survival rates are 70% in the transplanted group and 30% in the&#xD;
      resected group.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The protocol will comprise a phase 1 during which the potential eligibility of patients&#xD;
      (presenting with a resectable Klatskin - Excepted Type 1of Bismuth) will be assessed, based&#xD;
      on clinical, biological and morphological data. After phases 1, the eligibility of the&#xD;
      patient will be confirmed or not. In the context of the study, phase 2 will include the&#xD;
      collection of blood samples as well as positon emission tomography (PET)-scan and upper&#xD;
      endoscopic ultrasound (EUS) in order to rule out any obvious lymph node metastases. A short&#xD;
      exploratory laparoscopy will also be performed in phase 2 to eliminate infra-clinic&#xD;
      subcapsular liver metastases and peritoneal carcinomatosis. The randomization process will&#xD;
      take place at the end of the phase 2, patients will be assigned into the transplantation arm&#xD;
      (OLT) or the resection arm (RSX). During phase 3, patient will receive nutritional support&#xD;
      and, if not done previously, a biliary drainage will be placed endoscopically. In the RSX arm&#xD;
      (phase 3A), patients will undergo radical resection of the tumor (refer below technical&#xD;
      details). Preoperative portal vein embolization may be necessary at this stage depending on&#xD;
      the expected remnant liver volume, assessed by CT-scan volumetry. In the OLT arm (phase 3A),&#xD;
      patients will receive neoadjuvant radiochemotherapy (External - 50 grays) following by liver&#xD;
      transplantation (phase 4B). Before the fifth week after completion of radiochemotherapy, a&#xD;
      staging laparotomy with local lymphadenectomy will be performed and patients will be put on&#xD;
      the national waiting list in the absence of extra-hepatic disease, especially peritoneal&#xD;
      seeding and lymph nodes involvement. A score exception will allowed a liver transplantation&#xD;
      in the 3 months after staging laparotomy. During phase 5 the patient will be monitored&#xD;
      postoperatively at the clinical, biological and morphological levels for 3 months. During&#xD;
      phase 6, the patient will be followed clinically, biologically and morphologically for 5&#xD;
      years in order to detect any recurrence and in the context of standard clinical care.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>March 2014</start_date>
  <completion_date type="Anticipated">September 2024</completion_date>
  <primary_completion_date type="Anticipated">February 2024</primary_completion_date>
  <phase>N/A</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall survival</measure>
    <time_frame>At 5 years</time_frame>
    <description>To demonstrate the superiority, in terms of 5-year survival, of liver transplantation (TH) preceded by neoadjuvant chemoradiotherapy on the radical resection of Klatskin tumors considered resectable</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Recurrence free survival</measure>
    <time_frame>At 3 years</time_frame>
    <description>3-year recurrence-free survival assessed by CT and markers</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Cholangiocarcinoma</condition>
  <arm_group>
    <arm_group_label>CAPECITABINE-Radiotherapy -Liver Transplantation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Neoadjuvant Radio-Chemotherapy (RC) and Liver Transplantation (LT)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RESECTION</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Liver resection</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>CAPECITABINE-Radiotherapy -Liver Transplantation</intervention_name>
    <description>CAPECITABINE (800 mg/m2 twice a day during 5 weeks) + External Radiotherapy (50 grays during 5 weeks) then Liver transplantation</description>
    <arm_group_label>CAPECITABINE-Radiotherapy -Liver Transplantation</arm_group_label>
    <other_name>Neoadjuvant Radio-Chemotherapy and Liver Transplantation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>RESECTION</intervention_name>
    <description>Intent-to-treat R0 liver resection</description>
    <arm_group_label>RESECTION</arm_group_label>
    <other_name>Liver Resection</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients (male or female) aged from 18 to 68 year-old, French&#xD;
&#xD;
          -  Hilar cholangiocarcinoma histologically proved and/or highly suspected on hilar&#xD;
             stenosis with mass syndrome from 0.1 cm to 3 cm&#xD;
&#xD;
          -  Hilar cholangiocarcinoma type 2, type 3A, type 3B, type 4&#xD;
&#xD;
          -  Patients considered as resectable (R0 resection) by liver resection including segment&#xD;
             1 and biliary confluence with or without vascular resection&#xD;
&#xD;
          -  Patient potentially transplantable&#xD;
&#xD;
          -  Patient affiliated to French Health Insurance&#xD;
&#xD;
          -  Patient who had sign an informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breastfeeding woman&#xD;
&#xD;
          -  Women of childbearing potential without an effective contraception method&#xD;
&#xD;
          -  Radiotherapy contraindication&#xD;
&#xD;
          -  Positive dosage of ImmunoglobulinsG4 (IgG4)&#xD;
&#xD;
          -  dihydro-pyrimidine-dehydrogenase (DPD) total deficit&#xD;
&#xD;
          -  Personal history of cancer in the last 5 five years (exclusion basocellular cellular&#xD;
             carcinoma)&#xD;
&#xD;
          -  Personal history of fluoropyrimidine hypersensibility&#xD;
&#xD;
          -  Personal history of capecitabine hypersensibility&#xD;
&#xD;
          -  Personal history of dihydro-pyrimidine-dehydrogenase deficit&#xD;
&#xD;
          -  Polynuclear neutrophil &lt; 1500 / ml&#xD;
&#xD;
          -  Platelet rate &lt; 100 000 / ml&#xD;
&#xD;
          -  Severe leucopenia &lt; 2000 / ml&#xD;
&#xD;
          -  Severe liver failure (Factor V &lt; 50%)&#xD;
&#xD;
          -  Severe renal failure (Creatin clearance &lt; 30 ml/min)&#xD;
&#xD;
          -  Treatment by Sorivudine or its analogue as Brivudine&#xD;
&#xD;
          -  Non controled diabetes mellitus and/or others severe co-morbidities (renal failure,&#xD;
             severe and instable coronaropathy, severe risk factor of stroke, body mass index&#xD;
             superior to 35)&#xD;
&#xD;
          -  Proved histological cirrhosis&#xD;
&#xD;
          -  Sclerosing cholangitis&#xD;
&#xD;
          -  Intra and/or extra-hepatic metastases&#xD;
&#xD;
          -  Hypereosinophilia and/or wirsung dilatation and/or mass of the pancreas head&#xD;
&#xD;
          -  Hilar mass superior to 3 cm&#xD;
&#xD;
          -  Duodenal invasion&#xD;
&#xD;
          -  Patient under guardianship&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>68 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eric VIBERT, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>AP-HP, Paul Brousse Hospital, Centre Hepato-Biliaire, Villejuif, France</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>AP-HP, Paul Brousse Hospital, Centre Hepato-Biliaire</name>
      <address>
        <city>Villejuif</city>
        <zip>94</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>August 6, 2014</study_first_submitted>
  <study_first_submitted_qc>September 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2014</study_first_posted>
  <last_update_submitted>November 2, 2021</last_update_submitted>
  <last_update_submitted_qc>November 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hilar cholangiocarcinoma</keyword>
  <keyword>Liver transplantation</keyword>
  <keyword>Radiochemotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cholangiocarcinoma</mesh_term>
    <mesh_term>Klatskin Tumor</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Liver Extracts</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/NCT02232932
org study id: P120106
nct id: NCT02232932
lead sponsor: 
has dmc: Yes
A prospective, open-label, randomised, multicentre, comparative study in two parallel groups
      comparing an interventional group with liver transplantation preceded by neoadjuvant
      radio-chemotherapy and a control group receiving conventional liver and bile duct resection.

      The primary endpoint will be overall survival at 5 years in the intent-to-treat population.
      The secondary endpoint will be recurrence-free survival at 3 years evaluated by CT-scan and
      tumoral markers (Carcinoembryonic antigen (CAE) and cancer antigen (CA19.9)) in the
      intent-to-treat population.

      The number of subjects necessary is 54 patients (27 x 2): this population will enable the
      demonstration of a significant difference is 5-year survival rates between the transplanted
      group and the resected group with a power of 80% and a first-species risk of 5%, under the
      hypothesis that these survival rates are 70% in the transplanted group and 30% in the
      resected group.
The protocol will comprise a phase 1 during which the potential eligibility of patients
      (presenting with a resectable Klatskin - Excepted Type 1of Bismuth) will be assessed, based
      on clinical, biological and morphological data. After phases 1, the eligibility of the
      patient will be confirmed or not. In the context of the study, phase 2 will include the
      collection of blood samples as well as positon emission tomography (PET)-scan and upper
      endoscopic ultrasound (EUS) in order to rule out any obvious lymph node metastases. A short
      exploratory laparoscopy will also be performed in phase 2 to eliminate infra-clinic
      subcapsular liver metastases and peritoneal carcinomatosis. The randomization process will
      take place at the end of the phase 2, patients will be assigned into the transplantation arm
      (OLT) or the resection arm (RSX). During phase 3, patient will receive nutritional support
      and, if not done previously, a biliary drainage will be placed endoscopically. In the RSX arm
      (phase 3A), patients will undergo radical resection of the tumor (refer below technical
      details). Preoperative portal vein embolization may be necessary at this stage depending on
      the expected remnant liver volume, assessed by CT-scan volumetry. In the OLT arm (phase 3A),
      patients will receive neoadjuvant radiochemotherapy (External - 50 grays) following by liver
      transplantation (phase 4B). Before the fifth week after completion of radiochemotherapy, a
      staging laparotomy with local lymphadenectomy will be performed and patients will be put on
      the national waiting list in the absence of extra-hepatic disease, especially peritoneal
      seeding and lymph nodes involvement. A score exception will allowed a liver transplantation
      in the 3 months after staging laparotomy. During phase 5 the patient will be monitored
      postoperatively at the clinical, biological and morphological levels for 3 months. During
      phase 6, the patient will be followed clinically, biologically and morphologically for 5
      years in order to detect any recurrence and in the context of standard clinical care.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall survival
time frame: At 5 years
description: To demonstrate the superiority, in terms of 5-year survival, of liver transplantation (TH) preceded by neoadjuvant chemoradiotherapy on the radical resection of Klatskin tumors considered resectable
measure: Recurrence free survival
time frame: At 3 years
description: 3-year recurrence-free survival assessed by CT and markers
arm group label: CAPECITABINE-Radiotherapy -Liver Transplantation
arm group type: Experimental
description: Neoadjuvant Radio-Chemotherapy (RC) and Liver Transplantation (LT)
arm group label: RESECTION
arm group type: Active Comparator
description: Liver resection
intervention type: Procedure
intervention name: CAPECITABINE-Radiotherapy -Liver Transplantation
description: CAPECITABINE (800 mg/m2 twice a day during 5 weeks) + External Radiotherapy (50 grays during 5 weeks) then Liver transplantation
arm group label: CAPECITABINE-Radiotherapy -Liver Transplantation
other name: Neoadjuvant Radio-Chemotherapy and Liver Transplantation
intervention type: Procedure
intervention name: RESECTION
description: Intent-to-treat R0 liver resection
arm group label: RESECTION
other name: Liver Resection
criteria: 
gender: All
minimum age: 18 Years
maximum age: 68 Years
healthy volunteers: No
last name: Eric VIBERT, MD
role: Principal Investigator
affiliation: AP-HP, Paul Brousse Hospital, Centre Hepato-Biliaire, Villejuif, France
facility: 
country: France
responsible party type: Sponsor
mesh term: Cholangiocarcinoma
mesh term: Klatskin Tumor
mesh term: Capecitabine
mesh term: Liver Extracts