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Withdrawn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

About this trial
This is an interventional treatment trial for Carcinoma, Hepatocellular
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.
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
NCT ID
NCT01722175
First Posted
November 2, 2012
Last Updated
July 21, 2014
Sponsor
Washington University School of Medicine
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
Learn more about this trial
Associating Liver Partition With Portal Vein Ligation For Staged Hepatectomy (ALPPS) or Portal Vein Occlusion in Treating Patients With Liver Cancer
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