Associating Liver Partition With Portal Vein Ligation for Staged Hepatectomy (ALPPS) vs. Two-Stage Hepatectomy (TSH) for Marginally Resectable Colorectal Liver Metastases (CRLM)

NCT02758977 | Unknown DMC

• 1 other identifier: 2015-0024
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 1

Brief Summary

Surgical resection has offered the best option for prolonged survival in patients with colorectal liver metastases. Limiting factor for major liver resections is the size of the future liver remnant (FLR). In case of normal liver function, 30% of the total liver volume is considered to be sufficient to maintain adequate liver function after resection. In an attempt to further increase "resectability" criteria for patients with too small FLR surgical and interventional maneuvers such as portal vein embolization and portal vein ligation in two-stage hepatectomies have been implemented, but they need an interval of 4-8 weeks to achieve sufficient hypertrophy. In order to obtain adequate but rapid parenchymal hypertrophy a new surgical two-step technique, ALPPS, was introduced for oncological patients requiring extended hepatic resection with limited functional reserve. Both procedures can be performed with acceptable morbidity and mortality. The investigators conclude that it is time to perform a randomized study comparing the two surgical approaches in regard to oncological outcome.

Conditions

Colon Cancer Liver Metastases; Liver Neoplasms; Liver Diseases; Secondary Malignant Neoplasm of Liver; Malignant Neoplasm of Large Intestine Metastatic to Liver; Hepatectomy; Surgery

Keywords

Colorectal liver metastases; Liver Surgery; ALPPS; Two Stage Hepatectomy; Surgical Oncology; Hepatectomy

Outcome Measures

Primary Outcomes (1)

• 1 Year Disease-free Survival

  The primary objective will be disease-free survival at one year after randomization as determined by PET-CT (Positron emission tomography - Computer tomography), when not available by CT (Computer tomography) Thorax/Abdomen. This will be assessed by two independent radiologists who will be blinded to which arm the patient was enrolled in. Patients who died, are lost to follow up or are too sick to undergo imaging will be censored and counted as failures to reach the primary endpoint. Patients may need resection of their primary tumor after the study intervention (liver first strategy). They may develop recurrence within the study period, systemic or in the liver. In these patients ablation, reoperation and chemotherapy are used as customary clinical routine. Whether they achieved tumor free survival however depends only on the PET-CT or CT Thorax Abdomen at one year.

  1 year after Randomization

Secondary Outcomes (10)

• Procedure-associated Mortality

  Up to 1 year after Randomization

• Procedure-associated Complications

  Up to 1 year after Randomization

• Percentage of patients in which complete curative two-staged surgery was possible.

  Up to 1 year after Randomization

• Complete (R0) vs. incomplete (R1/2) resection (oncological outcome)

  1 year after Randomization

• Overall survival (oncological outcome)

  Up to 10 years after Randomization

Study Arms (2)

ALPPS

EXPERIMENTAL

ASSOCIATING LIVER PARTITION WITH PORTAL VEIN LIGATION FOR STAGED HEPATECTOMY (ALPPS) Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) is performed according to local practice in the respective centers. Preconditions to participation are experience with major liver resections and documentation of having performed at least 5 ALPPS cases prior to participation due to the learning curve with this quite complex procedure. The amount of transsection (in-situ split/liver partition) in Step 1 is left to the participating center, no minimal % of transsection is specified.

Procedure: ALPPS

TWO STAGE HEPATECTOMY

ACTIVE COMPARATOR

TWO STAGE HEPATECTOMY (TSH) Two-Stage Hepatectomy is defined as: 1. Partial resection + portal vein ligation (RES PVL) 2. Partial resection + secondary portal vein embolization (RES PVE). Followed by (extended) hemihepatectomy after an interval to induce hypertrophy of the liver. Conventional Two- Stage Hepatectomies will be standard procedures of the centers participating in the study.

Procedure: TWO STAGE HEPATECTOMY

Interventions

ALPPS PROCEDURE

For detailed information please refer to description of experimental arm

Also known as: Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy

ALPPS

TWO STAGE HEPATECTOMY PROCEDURE

For detailed information please refer to description of active comparator arm

Also known as: TSH

TWO STAGE HEPATECTOMY

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients above 18 years of age.
• Patients with multifocal CRLM with a FLR/TLV (Total Liver Volume)\< 30% OR a FLR/BW (Bodyweight) ratio of \< 0.5.
• Patients with colorectal primary tumor not yet resected may be included as long as the extrahepatic disease may be cured surgically (liver first strategy).
• Patients with lung metastases may be included in the study as long as the lung metastases are potentially curable by resection by judgment of a thoracic surgery consultant.
• Chemotherapy response according to RECIST: regression or stable disease.
• The indication for surgery should be discussed at a multidisciplinary tumor board attended by hepatobiliary surgeons, oncologists, hepatologists and radiologists.
• Written informed consent given by the patient after discussing the trial with the patient in a language he/she understands.

You may not qualify if:

• Male or female patients under 18 years of age.
• Unilobar tumorload qualifying the subject for a standard hepatectomy.
• Patients with multifocal CRLM with a FLR/TLV \> 30% OR a FLR/BW ratio of \> 0.5.
• Patients with a baseline FLR of less than 15%.
• Patients with extrahepatic metastatic disease (except potentially resectable lung metastases).
• Patients not having received chemotherapy before study enrollment.
• If the liver biopsy prior to enrollment or the first liver biopsy in stage I shows fibrosis (Metavir stage ≥F3) or \>30% macrosteatosis.
• Significant concomitant diseases making the patient unsuitable for major liver surgery by the judgment of the physicians involved.
• Known or suspected non-compliance (e.g. drug- and/or alcohol abuse).
• Enrollment into a clinical trial interfering with the endpoints.
• Intention to become pregnant during the course of the study.
• Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases.
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant.
• Previous enrollment in the current study.

Sponsors & Collaborators

• University of Zurich: lead

Study Sites (1)

University Hospital

Zurich, Canton of Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Liver Neoplasms; Liver Diseases

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases

Study Officials

• Pierre-Alain Clavien, MD, PhD

  University of Zurich

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marcel A Schneider, MD

CONTACT

0041 442553300; MarcelAndre.Schneider@usz.ch

Pierre-Alain Clavien, MD, PhD

CONTACT

0041 442553300; clavien@access.uzh.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2016
• First Posted: May 3, 2016
• Study Start: May 1, 2016
• Primary Completion: April 1, 2019
• Last Updated: May 3, 2016

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)