ALPPS Versus PVE/PL

Colorectal Cancer Clinical Trial

— LIGRO  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02215577
• Other study ID #: SweLiv 1-2014
• Status: Recruiting
• Phase: N/A
• First received: August 11, 2014
• Last updated: August 12, 2014
• Start date: June 2014
• Est. completion date: December 2018

Study information

• Verified date: August 2014
• Source: Regionalt Cancercentrum Väst
• Contact: Per Sandstrom, MD, PhD
• Phone: +46 73 4058581
• Email: per.sandstrom[@]liu.se
• Is FDA regulated: No
• Health authority: Sweden: Regional Ethical Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2018
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. By liver tumor board found accepted for inclusion

2. Patients with a tumor burden of colorectal liver metastasis

3. Signed informed content

4. Colorectal liver metastatic disease with an estimated FLR/sTLV of <30%

5. Primary tumor and any extrahepatic disease possible to resect in patients with liver first approach or after resection of primary tumor.

Exclusion Criteria:

1. Cirrhosis

2. Significant comorbidity rendering subjects unsuitable for major surgery

3. Progressive disease after preoperative oncological treatment

4. Age<18 years

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Liver Metastases

Intervention

Procedure:
• In-situ split
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.
• Portal embolization or ligation
Portal vein embolization is performed according to the intervention used at the different sites.

Locations

Country	Name	City	State
Denmark	Departments of Surgical Gastroenterology and Transplantation	Copenhagen
Norway	Rikshospitalet Oslo University Hospital	Oslo
Sweden	Sahlgrenska University Hospital	Gothenburg
Sweden	Department of Surgery, Linkoping University Hospital	Linkoping
Sweden	Department of Surgery, University Hospital	Lund
Sweden	Karolinska University Hospital	Stockholm
Sweden	Norrland University Hospital	Umea

Sponsors (1)

Lead Sponsor	Collaborator
Regionalt Cancercentrum Väst

Countries where clinical trial is conducted

Denmark,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Radical resection rate	Radical resection at resection line according to histopathology	8 weeks	No
Other	Composite complication rate	Overall complications will be analysed as a composite endpoint (CEP) including: ascites, postresectional liver failure, bile leak, intra abdominal bleeding, intraabdominal abscess and mortality, all with a Clavien score of at least 3	1 month after final surgery	Yes
Other	Treatment time	Treatment time in days from PVE/PL or date of ALPPS op 1 until date of leaving hospital after final surgery.	8 weeks	No
Other	Progression free survival	Progression free survival according to randomization group.	24 months	No
Other	Overall survival	Overall survival after inclusion	Up to 24 months after last inclusion	No
Other	Quality of life	Quality of life is measured by EORTC QLQ C-30 EQ5D ar 1,6,12,24 months.	24 months post final resection	No
Other	Health economy	An analysis with regard to hospitalisation rate and number of days in-ward between randomization arm.	At 8 weeks	No
Primary	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	Yes
Secondary	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	No