NCT02215577

Brief Summary

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.

Trial Health

47
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
100

participants targeted

Target at P25-P50 for not_applicable colorectal-cancer

Timeline
Completed

Started Jun 2014

Longer than P75 for not_applicable colorectal-cancer

Geographic Reach
3 countries

7 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2014

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

August 11, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 13, 2014

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2016

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2018

Completed
Last Updated

August 13, 2014

Status Verified

August 1, 2014

Enrollment Period

2.5 years

First QC Date

August 11, 2014

Last Update Submit

August 12, 2014

Conditions

Colorectal CancerLiver Metastases

Keywords

cancer, colorectalhepatectomyportal veinembolizationtwo-stage

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (1)

  • Liver growth rate

    At one week after primary intervention

Other Outcomes (7)

  • Radical resection rate

    8 weeks

  • Composite complication rate

    1 month after final surgery

  • Treatment time

    8 weeks

  • +4 more other outcomes

Study Arms (2)

In-situ split with portal vein ligature

EXPERIMENTAL

In-situ liver split at time when portal vein ligature is performed

Procedure: In-situ split

Portal embolization or ligation

ACTIVE COMPARATOR

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

Interventions

In-situ splitPROCEDURE

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.

Also known as: ALPPS
In-situ split with portal vein ligature
Portal embolization or ligationPROCEDURE

Portal vein embolization is performed according to the intervention used at the different sites.

Portal embolization or ligation

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • Cirrhosis
  • Significant comorbidity rendering subjects unsuitable for major surgery
  • Progressive disease after preoperative oncological treatment
  • Age\<18 years

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Departments of Surgical Gastroenterology and Transplantation

Copenhagen, Denmark

RECRUITING

Rikshospitalet Oslo University Hospital

Oslo, Norway

RECRUITING

Sahlgrenska University Hospital

Gothenburg, Sweden

RECRUITING

Department of Surgery, Linkoping University Hospital

Linköping, Sweden

RECRUITING

Department of Surgery, University Hospital

Lund, Sweden

RECRUITING

Karolinska University Hospital

Stockholm, Sweden

RECRUITING

Norrland University Hospital

Umeå, Sweden

RECRUITING

Related Publications (1)

  • Hasselgren K, Rosok BI, Larsen PN, Sparrelid E, Lindell G, Schultz NA, Bjornbeth BA, Isaksson B, Larsson AL, Rizell M, Bjornsson B, Sandstrom P. Response to Comment on: Hasselgren K, et al ALPPS Improves Survival Compared With TSH in Patients Affected of CRLM: Survival Analysis From the Randomized Controlled Trial LIGRO. Ann Surg. 2021;273(3):442-448. Ann Surg. 2022 Nov 1;276(5):e632-e633. doi: 10.1097/SLA.0000000000005268. Epub 2021 Oct 20. No abstract available.

    PMID: 35129514DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Ligation

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative

Central Study Contacts

Per Sandstrom, MD, PhD

CONTACT

+46 73 4058581per.sandstrom@liu.se

Magnus Rizell, MD, Phd

CONTACT

+46705259301magnus.rizell@surgery.gu.se

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 11, 2014

First Posted

August 13, 2014

Study Start

June 1, 2014

Primary Completion

December 1, 2016

Study Completion

December 1, 2018

Last Updated

August 13, 2014

Record last verified: 2014-08

Locations

SE(5)DK(1)NO(1)