A Randomized Controlled, Open-label, Multicentre Study Evaluating if Liver Transplantation With Liver Grafts From Extended Criteria Donors Not Utilised for Approved Indications Increases Overall Survival in Patients With Non-resectable Isolated Liver Metastases From Colorectal Metastases, in Comparison With Best Alternative Care

Vastra Gotaland Region2 sites in 1 country45 target enrollmentDecember 1, 2020

ConditionsColorectal Cancer Liver Metastases Colorectal Liver Metastases

Overview

Phase: Not Applicable
Intervention: Not specified
Conditions: Colorectal Cancer
Sponsor: Vastra Gotaland Region
Enrollment: 45
Locations: 2
Primary Endpoint: Five-year overall survival
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

To evaluate if the addition of liver transplantation primarily utilizing liver grafts from extended criteria donors not utilized for approved indications to conventional treatment of non-resectable/ non-abatable colorectal liver metastases (CLM) increases overall survival compared to best alternative care.

Registry

clinicaltrials.gov

Start Date

December 1, 2020

End Date

June 2030

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Vastra Gotaland Region

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients with non-resectable, non-ablatable liver metastases from colorectal adenocarcinoma.
•Male or female 18 years or above.
•Primary tumour removed with an R0 resection, and histologically verified adenocarcinoma from colon or rectum
•Liver metastases measurable by MRI or CT according to RECIST version 1.1 Imaging within 4 weeks prior to inclusion.
•No signs of extrahepatic metastatic disease or local recurrence according to MRI and CT of thorax/abdomen and whole body Positron-emission tomography (PET)/ computed tomography (CT) scan.
•A colonoscopy performed within the last 12 months in order to exclude multifocal colorectal cancer (CRC) tumours.
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
•Satisfactory blood tests: Hb ≥ 90 g/L (transfusions are permitted to achieve baseline hemoglobin level), White blood cell Count (WBC) \>3,0x109/L, Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L, platelet Count (PLT) \>75, Bilirubin\<2 x upper normal level, Aspartate aminotransferase (ASAT), Alanine aminotransferase (ALAT)\<5 x upper normal level, Calculated Creatinine clearance ≥ 50 mL/min(MDRD).
•Received at least 2 months of chemotherapy with no signs of progressive disease according to RECIST-criteria at the last evaluation before randomization.
•One year or more from the initial CRC diagnosis to the date of inclusion in the study

Exclusion Criteria

•Evidence of extrahepatic disease by PET-CT or CT-thorax/abdomen.
•Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study.
•Weight loss \>10% the last 6 months
•Other malignancies within the last 5 years, except CRC and low risk tumours such as basaliomas.
•\* Liver metastases larger than 10 cm.
•Pathological lymphatic nodes in the abdomen. If a patient has pathological lymphatic nodules in the hepatoduodenal ligament, a staging operation with histo-pathological examination from the nodules with no signs of tumour cell involvement has to be performed before inclusion.
•BRAF (a gene that encodes a protein called b-raf) mutation in primary tumour
•microsatellite instability (MSI-H) in primary tumour
•Previous organ transplantation

Outcomes

Primary Outcomes

Five-year overall survival

Time Frame: randomization to follow up at 5 years

Percentage of subject who reach the endpoint of overall survival

Secondary Outcomes

Hepatic progression-free survival(Date of randomization until the date of documented progression of existing lesions or appearance of new lesions in the liver, assessed up to 5 years)
Progression-free survival(Date of randomization until the date of documented progression of existing lesions or appearance of new lesions, assessed up to 5 years)
Extrahepatic recurrence-free survival(Date of randomization until the date of documented appearance of new extra-hepatic lesions, assessed up to 5 years)
Changes in quality of Life assessed with Euroqol Group Questionaire 5D-3L (EQ-5D-3L)(baseline, 3, 6, 12, 18, 24, 36 and 60 months)
Two-year overall survival(randomization to follow up at 2 years)
Median overall survival(: Date of randomization until the date of death from any cause, assessed up to 5 years)
Health economic evaluation(baseline, 3, 6, 12, 18, 24, 36 and 60 months)