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Associating Liver Partition With Portal Vein Ligation For Staged Hepatectomy (ALPPS) or Portal Vein Occlusion in Treating Patients With Liver Cancer (ALPPS)

Primary Purpose

Carcinoma, Hepatocellular

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
ALPPS surgery
PVO surgery
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Hepatocellular

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Patient may have primary or secondary hepatic malignancies with a FLR/TLV < 30% or a FLR/BW ratio of < 0.5 for patients with normal liver function (defined as normal transaminases, normal bilirubin, normal factor V, and normal PT/INR). In case of injury due to chemotherapy, known high grade steatosis, or cholestasis > 50 mmol/L, patient may be enrolled into the trial if FLR/TLV is < 40% or FLR/BW ratio < 0.8.
  • Patient must have extensive liver tumors that would require portal vein embolization or a two-stage hepatectomy and portal vein embolization or ligation by the judgment of surgeons in the tumor board.
  • Patient may have extrahepatic disease as long as it may be addressed after liver surgery and there is a tumor board decision to proceed with liver resection (mostly applicable to CRC metastases).
  • Patient may have received previous chemotherapy.
  • In cases of cholestasis, preoperative drainage procedures (PTC or ERCP) are left up to judgement of physicians.
  • Patient must be ≥ 18 years of age. The patient population over 65 years old needs to be carefully included based on comorbidities.
  • Patient may have undergone previous liver resection.
  • Patient's location must be such that proper staging and follow-up may be performed.
  • Patient's case must be presented at the Multidisciplinary Meeting attended by hepatobiliary surgeons, oncologists, hepatologists, and radiologists, or must be approved directly by Dr. Strasberg or Dr. Chapman.
  • Patient must be able to understand and willing to sign a written informed consent document.

Exclusion Criteria:

  • Patient must not have any significant concomitant diseases rendering him/her unsuitable for major liver surgery by the judgment of the physicians involved, especially if the patient is > 65 years old.
  • Patient must not have enrolled into a clinical trial within 4 weeks of study entry.
  • Patient must not have peritoneal carcinomatosis or other extensive extrahepatic disease.
  • Patient must not have advanced stages of carcinoma of the gallbladder (T3/T4)
  • Patient must not have issues such as drug and/or alcohol abuse.
  • Patient must not need major extrahepatic surgery (e.g. pancreas resection, gastric resection, rectal surgery) within 3 months of study entry.
  • Patient must not be a candidate for liver transplantation in case of HCC.
  • Patient must not be pregnant or breastfeeding. If a female of childbearing potential, patient must have a negative pregnancy test within 14 days of enrollment.

Inclusion of Women and Minorities

-Both men and women and members of all races and ethnic groups are eligible for this trial.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Arm I (ALPPS)

    Arm II (PVO)

    Arm 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.

    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.

    Outcomes

    Primary Outcome Measures

    Liver free of tumors
    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.

    Secondary Outcome Measures

    Overall survival
    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.
    Disease-free survival
    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.
    Incidence of complications
    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.
    Liver volumetric change after step 1 of ALPPS or PVO
    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
    Liver synthetic and transport function
    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.

    Full Information

    First Posted
    November 2, 2012
    Last Updated
    July 21, 2014
    Sponsor
    Washington University School of Medicine
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01722175
    Brief Title
    Associating Liver Partition With Portal Vein Ligation For Staged Hepatectomy (ALPPS) or Portal Vein Occlusion in Treating Patients With Liver Cancer
    Acronym
    ALPPS
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2014
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Safety concerns.
    Study Start Date
    undefined (undefined)
    Primary Completion Date
    April 2016 (Anticipated)
    Study Completion Date
    January 2019 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Washington University School of Medicine

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Carcinoma, Hepatocellular

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    Outcomes Assessor
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Arm I (ALPPS)
    Arm Type
    Experimental
    Arm 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 Title
    Arm II (PVO)
    Arm Type
    Active Comparator
    Arm 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(s)
    ALPPS surgery
    Intervention Type
    Procedure
    Intervention Name(s)
    PVO surgery
    Primary Outcome Measure Information:
    Title
    Liver free of tumors
    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.
    Time Frame
    At 3 months
    Secondary Outcome Measure Information:
    Title
    Overall survival
    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.
    Time Frame
    Up to 3 years
    Title
    Disease-free survival
    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.
    Time Frame
    Up to 3 years
    Title
    Incidence of complications
    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.
    Time Frame
    3 months
    Title
    Liver volumetric change after step 1 of ALPPS or PVO
    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
    Time Frame
    8 weeks
    Title
    Liver synthetic and transport function
    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.
    Time Frame
    3 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Patient may have primary or secondary hepatic malignancies with a FLR/TLV < 30% or a FLR/BW ratio of < 0.5 for patients with normal liver function (defined as normal transaminases, normal bilirubin, normal factor V, and normal PT/INR). In case of injury due to chemotherapy, known high grade steatosis, or cholestasis > 50 mmol/L, patient may be enrolled into the trial if FLR/TLV is < 40% or FLR/BW ratio < 0.8. Patient must have extensive liver tumors that would require portal vein embolization or a two-stage hepatectomy and portal vein embolization or ligation by the judgment of surgeons in the tumor board. Patient may have extrahepatic disease as long as it may be addressed after liver surgery and there is a tumor board decision to proceed with liver resection (mostly applicable to CRC metastases). Patient may have received previous chemotherapy. In cases of cholestasis, preoperative drainage procedures (PTC or ERCP) are left up to judgement of physicians. Patient must be ≥ 18 years of age. The patient population over 65 years old needs to be carefully included based on comorbidities. Patient may have undergone previous liver resection. Patient's location must be such that proper staging and follow-up may be performed. Patient's case must be presented at the Multidisciplinary Meeting attended by hepatobiliary surgeons, oncologists, hepatologists, and radiologists, or must be approved directly by Dr. Strasberg or Dr. Chapman. Patient must be able to understand and willing to sign a written informed consent document. Exclusion Criteria: Patient must not have any significant concomitant diseases rendering him/her unsuitable for major liver surgery by the judgment of the physicians involved, especially if the patient is > 65 years old. Patient must not have enrolled into a clinical trial within 4 weeks of study entry. Patient must not have peritoneal carcinomatosis or other extensive extrahepatic disease. Patient must not have advanced stages of carcinoma of the gallbladder (T3/T4) Patient must not have issues such as drug and/or alcohol abuse. Patient must not need major extrahepatic surgery (e.g. pancreas resection, gastric resection, rectal surgery) within 3 months of study entry. Patient must not be a candidate for liver transplantation in case of HCC. Patient must not be pregnant or breastfeeding. If a female of childbearing potential, patient must have a negative pregnancy test within 14 days of enrollment. Inclusion of Women and Minorities -Both men and women and members of all races and ethnic groups are eligible for this trial.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Steven Strasberg, M.D.
    Organizational Affiliation
    Washington University School of Medicine
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Links:
    URL
    http://www.siteman.wustl.edu
    Description
    Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

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