ALPPS Versus PVE/PL

Study Overview
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Brief Summary
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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.

Official Title
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Comparison of Two Different Models of Liver Growth Stimulation in Advanced Colorectal Liver Metastatic Disease, (LIGRO Trial) Enabling Liver Resection

Conditions
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Colorectal Cancer, Liver Metastases

Intervention / Treatment
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* Procedure: In-situ split
* Procedure: Portal embolization or ligation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: By liver tumor board found accepted for inclusion Patients with a tumor burden of colorectal liver metastasis Signed informed content Colorectal liver metastatic disease with an estimated FLR/sTLV of <30% Primary tumor and any extrahepatic disease possible to resect in patients with liver first approach or after resection of primary tumor. Exclusion Criteria: Cirrhosis Significant comorbidity rendering subjects unsuitable for major surgery Progressive disease after preoperative oncological treatment Age<18 years

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: In-situ split with portal vein ligature<br>In-situ liver split at time when portal vein ligature is performed | Procedure: In-situ split<br>* 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.<br>* Other names: ALPPS;|
| Active Comparator: Portal embolization or ligation<br>Intervention: Preoperative portal embolization (+/-ablation) followed by liver resection, or local resections and/or ablations followed by lobectomy, two-stage hepatectomy | Procedure: Portal embolization or ligation<br>* Portal vein embolization is performed according to the intervention used at the different sites.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Surgical success rate, the rate of liver resection in each study arm | 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. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver growth rate | 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. | At one week after primary intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer, colorectal, hepatectomy, portal vein, embolization, two-stage