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

NCT ID: NCT02758977

Last Updated: 2016-05-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 214 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

ALPPS

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.

Group Type: EXPERIMENTAL

ALPPS

Intervention Type: PROCEDURE

For detailed information please refer to description of experimental arm

TWO STAGE HEPATECTOMY

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.

Group Type: ACTIVE_COMPARATOR

TWO STAGE HEPATECTOMY

Intervention Type: PROCEDURE

For detailed information please refer to description of active comparator arm

Interventions

ALPPS

For detailed information please refer to description of experimental arm

Intervention Type: PROCEDURE

TWO STAGE HEPATECTOMY

For detailed information please refer to description of active comparator arm

Intervention Type: PROCEDURE

Other Intervention Names

Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy; TSH

Eligibility Criteria

Inclusion Criteria

• 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.
• For women of chlidbearing age: Not currently breastfeeding; usage of effective contraception if sexually active; not pregnant and agreement not to become pregnant during the 12 months thereafter. A negative pregnancy test before inclusion into the trial is required for women, who are not yet menopausal, had their last menses within less than 12 months or have not had uterus and or ovaries removed surgically or undergone tubal ligation.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pierre-Alain Clavien, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Zurich

Locations

University Hospital

Zurich, Canton of Zurich, Switzerland

Countries

Switzerland

Central Contacts

Marcel A Schneider, MD

Role: CONTACT

MarcelAndre.Schneider@usz.ch

0041 442553300

Pierre-Alain Clavien, MD, PhD

Role: CONTACT

clavien@access.uzh.ch

0041 442553300

Facility Contacts

Marcel A Schneider, MD

Role: primary

MarcelAndre.Schneider@usz.ch

0041 442553300

Pierre-Alain Clavien, MD PhD

Role: backup

clavien@access.uzh.ch

0041 442553300

Other Identifiers

2015-0024

Identifier Type: -

Identifier Source: org_study_id