<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/NCT01722175</url>
  </required_header>
  <id_info>
    <org_study_id>201209123</org_study_id>
    <nct_id>NCT01722175</nct_id>
  </id_info>
  <brief_title>Associating Liver Partition With Portal Vein Ligation For Staged Hepatectomy (ALPPS) or Portal Vein Occlusion in Treating Patients With Liver Cancer</brief_title>
  <acronym>ALPPS</acronym>
  <official_title>Associating Liver Partition With Portal Vein Ligation for Staged Hepatectomy (ALPPS) Versus Portal Vein Occlusion (PVO) to Induce Liver Regeneration for Resection of Liver Tumors That Are Unresectable in One Step - a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized phase II trial compares how well associating liver partition with portal vein&#xD;
      ligation for staged hepatectomy (ALPPS) or portal vein occlusion (PVO) works in treating&#xD;
      patients with liver cancer. Both treatments are types of 2-stage hepatectomies for removing&#xD;
      liver cancer. ALPPS may be more effective than PVO in patients whose disease would&#xD;
      traditionally be considered inoperable.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Safety concerns.&#xD;
  </why_stopped>
  <completion_date type="Anticipated">January 2019</completion_date>
  <primary_completion_date type="Anticipated">April 2016</primary_completion_date>
  <phase>Phase 2</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Liver free of tumors</measure>
    <time_frame>At 3 months</time_frame>
    <description>Assessed by two independent and blinded radiologists using dynamic MRI with liver specific contrast; proportion of patients in each treatment arm; incidence across two arms will be summarized using contingency tables and compared by 2-sample Chi-square test or Fisher's exact test.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Kaplan-Meier product limit estimator will be used to describe the distribution of overall survival (OS). The differences in OS between treatment arms will be compared using log-rank test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-free survival</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Kaplan-Meier product limit estimator will be used to describe the distribution disease-free survival (DFS). The differences in DFS between treatment arms will be compared using log-rank test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of complications</measure>
    <time_frame>3 months</time_frame>
    <description>Each patient will be categorized according to the most severe complication occurring during the two procedures of each arm; distributions across two arms will be compared by 2-sample Chi-square test or Fisher's exact test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver volumetric change after step 1 of ALPPS or PVO</measure>
    <time_frame>8 weeks</time_frame>
    <description>Assessed at 1, 2, 4 and 8 weeks after step 1 using CT or MRI imaging; differences between two arms will be compared using 2-way ANOVA for repeated measurement data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver synthetic and transport function</measure>
    <time_frame>3 months</time_frame>
    <description>PT/INR, factor V and bilirumen are measured; differences between two treatment arms will be compared using t-test or Mann-Whitney rank-sum test as appropriate.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Carcinoma, Hepatocellular</condition>
  <arm_group>
    <arm_group_label>Arm I (ALPPS)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergo Associating Liver Partition with Portal Vein Ligation (ALPPS) step 1 surgery on day 0 and step 2 surgery 7-14 days later, based on patient's liver size.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (PVO)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients undergo portal vein occlusion (PVO) step 1 on day 0 and step 2 surgery 6-8 weeks later, based on patient's liver size.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>ALPPS surgery</intervention_name>
    <arm_group_label>Arm I (ALPPS)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>PVO surgery</intervention_name>
    <arm_group_label>Arm II (PVO)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient may have primary or secondary hepatic malignancies with a FLR/TLV &lt; 30% or a&#xD;
             FLR/BW ratio of &lt; 0.5 for patients with normal liver function (defined as normal&#xD;
             transaminases, normal bilirubin, normal factor V, and normal PT/INR). In case of&#xD;
             injury due to chemotherapy, known high grade steatosis, or cholestasis &gt; 50 mmol/L,&#xD;
             patient may be enrolled into the trial if FLR/TLV is &lt; 40% or FLR/BW ratio &lt; 0.8.&#xD;
&#xD;
          -  Patient must have extensive liver tumors that would require portal vein embolization&#xD;
             or a two-stage hepatectomy and portal vein embolization or ligation by the judgment of&#xD;
             surgeons in the tumor board.&#xD;
&#xD;
          -  Patient may have extrahepatic disease as long as it may be addressed after liver&#xD;
             surgery and there is a tumor board decision to proceed with liver resection (mostly&#xD;
             applicable to CRC metastases).&#xD;
&#xD;
          -  Patient may have received previous chemotherapy.&#xD;
&#xD;
          -  In cases of cholestasis, preoperative drainage procedures (PTC or ERCP) are left up to&#xD;
             judgement of physicians.&#xD;
&#xD;
          -  Patient must be ≥ 18 years of age. The patient population over 65 years old needs to&#xD;
             be carefully included based on comorbidities.&#xD;
&#xD;
          -  Patient may have undergone previous liver resection.&#xD;
&#xD;
          -  Patient's location must be such that proper staging and follow-up may be performed.&#xD;
&#xD;
          -  Patient's case must be presented at the Multidisciplinary Meeting attended by&#xD;
             hepatobiliary surgeons, oncologists, hepatologists, and radiologists, or must be&#xD;
             approved directly by Dr. Strasberg or Dr. Chapman.&#xD;
&#xD;
          -  Patient must be able to understand and willing to sign a written informed consent&#xD;
             document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient must not have any significant concomitant diseases rendering him/her&#xD;
             unsuitable for major liver surgery by the judgment of the physicians involved,&#xD;
             especially if the patient is &gt; 65 years old.&#xD;
&#xD;
          -  Patient must not have enrolled into a clinical trial within 4 weeks of study entry.&#xD;
&#xD;
          -  Patient must not have peritoneal carcinomatosis or other extensive extrahepatic&#xD;
             disease.&#xD;
&#xD;
          -  Patient must not have advanced stages of carcinoma of the gallbladder (T3/T4)&#xD;
&#xD;
          -  Patient must not have issues such as drug and/or alcohol abuse.&#xD;
&#xD;
          -  Patient must not need major extrahepatic surgery (e.g. pancreas resection, gastric&#xD;
             resection, rectal surgery) within 3 months of study entry.&#xD;
&#xD;
          -  Patient must not be a candidate for liver transplantation in case of HCC.&#xD;
&#xD;
          -  Patient must not be pregnant or breastfeeding. If a female of childbearing potential,&#xD;
             patient must have a negative pregnancy test within 14 days of enrollment.&#xD;
&#xD;
        Inclusion of Women and Minorities&#xD;
&#xD;
        -Both men and women and members of all races and ethnic groups are eligible for this trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven Strasberg, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <link>
    <url>http://www.siteman.wustl.edu</url>
    <description>Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine</description>
  </link>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>November 2, 2012</study_first_submitted>
  <study_first_submitted_qc>November 2, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 6, 2012</study_first_posted>
  <last_update_submitted>July 21, 2014</last_update_submitted>
  <last_update_submitted_qc>July 21, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 22, 2014</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>Carcinoma, Hepatocellular</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/NCT01722175
org study id: 201209123
nct id: NCT01722175
lead sponsor: 
has dmc: No
This randomized phase II trial compares how well associating liver partition with portal vein
      ligation for staged hepatectomy (ALPPS) or portal vein occlusion (PVO) works in treating
      patients with liver cancer. Both treatments are types of 2-stage hepatectomies for removing
      liver cancer. ALPPS may be more effective than PVO in patients whose disease would
      traditionally be considered inoperable.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Liver free of tumors
time frame: At 3 months
description: Assessed by two independent and blinded radiologists using dynamic MRI with liver specific contrast; proportion of patients in each treatment arm; incidence across two arms will be summarized using contingency tables and compared by 2-sample Chi-square test or Fisher's exact test.
measure: Overall survival
time frame: Up to 3 years
description: Kaplan-Meier product limit estimator will be used to describe the distribution of overall survival (OS). The differences in OS between treatment arms will be compared using log-rank test.
measure: Disease-free survival
time frame: Up to 3 years
description: Kaplan-Meier product limit estimator will be used to describe the distribution disease-free survival (DFS). The differences in DFS between treatment arms will be compared using log-rank test.
measure: Incidence of complications
time frame: 3 months
description: Each patient will be categorized according to the most severe complication occurring during the two procedures of each arm; distributions across two arms will be compared by 2-sample Chi-square test or Fisher's exact test.
measure: Liver volumetric change after step 1 of ALPPS or PVO
time frame: 8 weeks
description: Assessed at 1, 2, 4 and 8 weeks after step 1 using CT or MRI imaging; differences between two arms will be compared using 2-way ANOVA for repeated measurement data
measure: Liver synthetic and transport function
time frame: 3 months
description: PT/INR, factor V and bilirumen are measured; differences between two treatment arms will be compared using t-test or Mann-Whitney rank-sum test as appropriate.
arm group label: Arm I (ALPPS)
arm group type: Experimental
description: Patients undergo Associating Liver Partition with Portal Vein Ligation (ALPPS) step 1 surgery on day 0 and step 2 surgery 7-14 days later, based on patient's liver size.
arm group label: Arm II (PVO)
arm group type: Active Comparator
description: Patients undergo portal vein occlusion (PVO) step 1 on day 0 and step 2 surgery 6-8 weeks later, based on patient's liver size.
intervention type: Procedure
intervention name: ALPPS surgery
arm group label: Arm I (ALPPS)
intervention type: Procedure
intervention name: PVO surgery
arm group label: Arm II (PVO)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Steven Strasberg, M.D.
role: Principal Investigator
affiliation: Washington University School of Medicine
country: United States
url: http://www.siteman.wustl.edu
description: Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
responsible party type: Sponsor
mesh term: Carcinoma, Hepatocellular