Clinical trial NCT02758977: Associating Liver Partition With Portal Vein Ligation for Staged Hepatectomy (ALPPS) vs. Two-Stage Hepatectomy (TSH) for Marginally Resectable Colorectal Liver Metastases (CRLM)
Official title: Associating Liver Partition With Portal Vein Ligation for Staged Hepatectomy (ALPPS) vs. Conventional Two-Stage Hepatectomy (TSH) for Surgical Treatment of Marginally Resectable Colorectal Liver Metastases (CRLM) - A Multicentric, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
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
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2016-05-03
Enrollment: 214
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

Patients fulfilling all of the following inclusion criteria may be enrolled in the study:

* 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:

The presence of any one of the following exclusion criteria will lead to exclusion of the participant:

* 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.

Primary outcomes:
measure: 1 Year Disease-free Survival
timeFrame: 1 year after Randomization
Secondary outcomes:
measure: Procedure-associated Mortality
timeFrame: Up to 1 year after Randomization
measure: Procedure-associated Complications
timeFrame: Up to 1 year after Randomization
measure: Percentage of patients in which complete curative two-staged surgery was possible.
timeFrame: Up to 1 year after Randomization
measure: Complete (R0) vs. incomplete (R1/2) resection (oncological outcome)
timeFrame: 1 year after Randomization
measure: Overall survival (oncological outcome)
timeFrame: Up to 10 years after Randomization
measure: Quality of Life (QoL)
timeFrame: Up to 1 year after Randomization
measure: Radiographic liver volumetric changes
timeFrame: Up to 1 year after Randomization
measure: Incidence of posthepatectomy liver failure
timeFrame: Up to 1 year after Randomization
measure: Incidence of posthepatectomy liver failure
timeFrame: Up to 1 year after Randomization
measure: Incidence of posthepatectomy renal failure
timeFrame: Up to 1 year after Randomization
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital
state: ZH
Study officials:
affiliation: University of Zurich
name: Pierre-Alain Clavien, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: