<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/NCT02215577</url>
  </required_header>
  <id_info>
    <org_study_id>SweLiv 1-2014</org_study_id>
    <nct_id>NCT02215577</nct_id>
  </id_info>
  <brief_title>ALPPS Versus PVE/PL</brief_title>
  <acronym>LIGRO</acronym>
  <official_title>Comparison of Two Different Models of Liver Growth Stimulation in Advanced Colorectal Liver Metastatic Disease, (LIGRO Trial) Enabling Liver Resection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Regionalt Cancercentrum Väst</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Regionalt Cancercentrum Väst</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study Title Comparison of two different models of liver growth stimulation in advanced&#xD;
      colorectal liver metastatic disease, (LIGRO Trial) enabling liver resection&#xD;
&#xD;
      Methodology Scandinavian Multiple Center Randomized Registry Based Clinical Trial&#xD;
&#xD;
      Study duration The planned duration of study participation for an individual subject from&#xD;
      inclusion to follow-up are 3 years&#xD;
&#xD;
      Primary investigator:&#xD;
&#xD;
      Per Sandstrom (Linköping)&#xD;
&#xD;
      Number of subjects 100 patients randomized in a 1:1 randomization&#xD;
&#xD;
      Diagnosis and main inclusion criteria Patients with colorectal liver metastasis requiring&#xD;
      liver resection, but are not resectable in one step because of a future liver&#xD;
      remnant/standardized total liver volume of &lt; 30 % extrahepatic metastatic disease is not an&#xD;
      exclusion criteria if they can be addressed surgically in the future&#xD;
&#xD;
      Overall goal To evaluate if the ALPPS approach is superior to PVE in enabling patients,&#xD;
      primarily unresectable due to inadequate FLR, to be resected and reach an R0 situation with&#xD;
      an acceptable level of complications and perioperative mortality.&#xD;
&#xD;
      To evaluate if the ALPPS approach increases the growth rate of the liver compared to portal&#xD;
      embolization or portal ligation leading to a shorter treatment period.&#xD;
&#xD;
      In addition the investigators aim to study if ALPPS may reach these goals without detectable&#xD;
      or improved differences in tumor activity (PFS and OS), but with a shorter recovery and a&#xD;
      higher proportion of patients reaching R0.&#xD;
&#xD;
      Hypothesis A higher proportion of patients can be resected with ALPPS counted as rate&#xD;
      resected compared to the previously established methods with portal ligation or embolization.&#xD;
&#xD;
      This increased resection rate will not reduce the R0 rate, or increase the rate of Clavien&#xD;
      grade 4 complication or higher (H0).&#xD;
&#xD;
      The ALPPS approach will increase the growth rate compared to portal embolization/ligation&#xD;
      measured one week after the primary intervention.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>June 2014</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">December 2016</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Surgical success rate, the rate of liver resection in each study arm</measure>
    <time_frame>8 weeks</time_frame>
    <description>For both the ALPPS and the portal vein embolization/ligation arm, resection is not allowed within the study if the patient is not reaching a future liver remnant of 30%.&#xD;
For both groups carcinomatosis or more metastases making aiming radical resections impossible will be seen as failures.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Liver growth rate</measure>
    <time_frame>At one week after primary intervention</time_frame>
    <description>Liver growth is measured with regard to the future liver remnant by measuring the kinetic growth rate by performing repeated CT or MRI at one week after portal vein embolization/ligation or after the first step of the ALPPS procedure.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Radical resection rate</measure>
    <time_frame>8 weeks</time_frame>
    <description>Radical resection at resection line according to histopathology</description>
  </other_outcome>
  <other_outcome>
    <measure>Composite complication rate</measure>
    <time_frame>1 month after final surgery</time_frame>
    <description>Overall complications will be analysed as a composite endpoint (CEP) including: ascites, postresectional liver failure, bile leak, intra abdominal bleeding, intraabdominal abscess and mortality, all with a Clavien score of at least 3</description>
  </other_outcome>
  <other_outcome>
    <measure>Treatment time</measure>
    <time_frame>8 weeks</time_frame>
    <description>Treatment time in days from PVE/PL or date of ALPPS op 1 until date of leaving hospital after final surgery.</description>
  </other_outcome>
  <other_outcome>
    <measure>Progression free survival</measure>
    <time_frame>24 months</time_frame>
    <description>Progression free survival according to randomization group.</description>
  </other_outcome>
  <other_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to 24 months after last inclusion</time_frame>
    <description>Overall survival after inclusion</description>
  </other_outcome>
  <other_outcome>
    <measure>Quality of life</measure>
    <time_frame>24 months post final resection</time_frame>
    <description>Quality of life is measured by EORTC QLQ C-30 EQ5D ar 1,6,12,24 months.</description>
  </other_outcome>
  <other_outcome>
    <measure>Health economy</measure>
    <time_frame>At 8 weeks</time_frame>
    <description>An analysis with regard to hospitalisation rate and number of days in-ward between randomization arm.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Colorectal Cancer</condition>
  <condition>Liver Metastases</condition>
  <arm_group>
    <arm_group_label>In-situ split with portal vein ligature</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In-situ liver split at time when portal vein ligature is performed</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Portal embolization or ligation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intervention: Preoperative portal embolization (+/-ablation) followed by liver resection, or local resections and/or ablations followed by lobectomy, two-stage hepatectomy</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>In-situ split</intervention_name>
    <description>The portal branches to the diseased side should be completely divided. The bile duct to the diseased side should not be divided. The parenchyma should be transected all the way through the transection plane and place a plastic sheet on the diseased transection surface.</description>
    <arm_group_label>In-situ split with portal vein ligature</arm_group_label>
    <other_name>ALPPS</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Portal embolization or ligation</intervention_name>
    <description>Portal vein embolization is performed according to the intervention used at the different sites.</description>
    <arm_group_label>Portal embolization or ligation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. By liver tumor board found accepted for inclusion&#xD;
&#xD;
          2. Patients with a tumor burden of colorectal liver metastasis&#xD;
&#xD;
          3. Signed informed content&#xD;
&#xD;
          4. Colorectal liver metastatic disease with an estimated FLR/sTLV of &lt;30%&#xD;
&#xD;
          5. Primary tumor and any extrahepatic disease possible to resect in patients with liver&#xD;
             first approach or after resection of primary tumor.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Cirrhosis&#xD;
&#xD;
          2. Significant comorbidity rendering subjects unsuitable for major surgery&#xD;
&#xD;
          3. Progressive disease after preoperative oncological treatment&#xD;
&#xD;
          4. Age&lt;18 years&#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_contact>
    <last_name>Per Sandstrom, MD, PhD</last_name>
    <phone>+46 73 4058581</phone>
    <email>per.sandstrom@liu.se</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Magnus Rizell, MD, Phd</last_name>
    <phone>+46705259301</phone>
    <email>magnus.rizell@surgery.gu.se</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Departments of Surgical Gastroenterology and Transplantation</name>
      <address>
        <city>Copenhagen</city>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Peter Noergard Larsen, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Rikshospitalet Oslo University Hospital</name>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bard Rosak, MD, PhD</last_name>
      <email>brosok@ous-hf.no</email>
    </contact>
    <investigator>
      <last_name>Bard Rosok, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sahlgrenska University Hospital</name>
      <address>
        <city>Gothenburg</city>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Magnus Rizell</last_name>
    </contact>
    <investigator>
      <last_name>Magnus Rizell, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Department of Surgery, Linkoping University Hospital</name>
      <address>
        <city>Linkoping</city>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Per Sandstrom, PhD, MD</last_name>
    </contact>
    <investigator>
      <last_name>Per Sandstrom, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Department of Surgery, University Hospital</name>
      <address>
        <city>Lund</city>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gert Lindell, MD, PhD</last_name>
      <phone>+46707190077</phone>
      <email>Gert.Lindell@skane.se</email>
    </contact>
    <investigator>
      <last_name>Gert Lindell, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Karolinska University Hospital</name>
      <address>
        <city>Stockholm</city>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bengt Isaksson, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Bengt Isaksson, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Norrland University Hospital</name>
      <address>
        <city>Umea</city>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bjarne Andnor, MD</last_name>
    </contact>
    <investigator>
      <last_name>Bjarne Andnor, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>Norway</country>
    <country>Sweden</country>
  </location_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 11, 2014</study_first_submitted>
  <study_first_submitted_qc>August 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <last_update_submitted>August 12, 2014</last_update_submitted>
  <last_update_submitted_qc>August 12, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 13, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>cancer, colorectal</keyword>
  <keyword>hepatectomy</keyword>
  <keyword>portal vein</keyword>
  <keyword>embolization</keyword>
  <keyword>two-stage</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</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/NCT02215577
org study id: SweLiv 1-2014
nct id: NCT02215577
lead sponsor: 
has dmc: Yes
Study Title Comparison of two different models of liver growth stimulation in advanced
      colorectal liver metastatic disease, (LIGRO Trial) enabling liver resection

      Methodology Scandinavian Multiple Center Randomized Registry Based Clinical Trial

      Study duration The planned duration of study participation for an individual subject from
      inclusion to follow-up are 3 years

      Primary investigator:

      Per Sandstrom (Linköping)

      Number of subjects 100 patients randomized in a 1:1 randomization

      Diagnosis and main inclusion criteria Patients with colorectal liver metastasis requiring
      liver resection, but are not resectable in one step because of a future liver
      remnant/standardized total liver volume of < 30 % extrahepatic metastatic disease is not an
      exclusion criteria if they can be addressed surgically in the future

      Overall goal To evaluate if the ALPPS approach is superior to PVE in enabling patients,
      primarily unresectable due to inadequate FLR, to be resected and reach an R0 situation with
      an acceptable level of complications and perioperative mortality.

      To evaluate if the ALPPS approach increases the growth rate of the liver compared to portal
      embolization or portal ligation leading to a shorter treatment period.

      In addition the investigators aim to study if ALPPS may reach these goals without detectable
      or improved differences in tumor activity (PFS and OS), but with a shorter recovery and a
      higher proportion of patients reaching R0.

      Hypothesis A higher proportion of patients can be resected with ALPPS counted as rate
      resected compared to the previously established methods with portal ligation or embolization.

      This increased resection rate will not reduce the R0 rate, or increase the rate of Clavien
      grade 4 complication or higher (H0).

      The ALPPS approach will increase the growth rate compared to portal embolization/ligation
      measured one week after the primary intervention.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Surgical success rate, the rate of liver resection in each study arm
time frame: 8 weeks
description: For both the ALPPS and the portal vein embolization/ligation arm, resection is not allowed within the study if the patient is not reaching a future liver remnant of 30%.
For both groups carcinomatosis or more metastases making aiming radical resections impossible will be seen as failures.
measure: Liver growth rate
time frame: At one week after primary intervention
description: Liver growth is measured with regard to the future liver remnant by measuring the kinetic growth rate by performing repeated CT or MRI at one week after portal vein embolization/ligation or after the first step of the ALPPS procedure.
measure: Radical resection rate
time frame: 8 weeks
description: Radical resection at resection line according to histopathology
measure: Composite complication rate
time frame: 1 month after final surgery
description: Overall complications will be analysed as a composite endpoint (CEP) including: ascites, postresectional liver failure, bile leak, intra abdominal bleeding, intraabdominal abscess and mortality, all with a Clavien score of at least 3
measure: Treatment time
time frame: 8 weeks
description: Treatment time in days from PVE/PL or date of ALPPS op 1 until date of leaving hospital after final surgery.
measure: Progression free survival
time frame: 24 months
description: Progression free survival according to randomization group.
measure: Overall survival
time frame: Up to 24 months after last inclusion
description: Overall survival after inclusion
measure: Quality of life
time frame: 24 months post final resection
description: Quality of life is measured by EORTC QLQ C-30 EQ5D ar 1,6,12,24 months.
measure: Health economy
time frame: At 8 weeks
description: An analysis with regard to hospitalisation rate and number of days in-ward between randomization arm.
arm group label: In-situ split with portal vein ligature
arm group type: Experimental
description: In-situ liver split at time when portal vein ligature is performed
arm group label: Portal embolization or ligation
arm group type: Active Comparator
description: Intervention: Preoperative portal embolization (+/-ablation) followed by liver resection, or local resections and/or ablations followed by lobectomy, two-stage hepatectomy
intervention type: Procedure
intervention name: In-situ split
description: The portal branches to the diseased side should be completely divided. The bile duct to the diseased side should not be divided. The parenchyma should be transected all the way through the transection plane and place a plastic sheet on the diseased transection surface.
arm group label: In-situ split with portal vein ligature
other name: ALPPS
intervention type: Procedure
intervention name: Portal embolization or ligation
description: Portal vein embolization is performed according to the intervention used at the different sites.
arm group label: Portal embolization or ligation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Per Sandstrom, MD, PhD
phone: +46 73 4058581
email: per.sandstrom@liu.se
last name: Magnus Rizell, MD, Phd
phone: +46705259301
email: magnus.rizell@surgery.gu.se
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Denmark
country: Norway
country: Sweden
responsible party type: Sponsor
mesh term: Colorectal Neoplasms