Colorectal Cancer, Colorectal Liver Metastases, Liver Metastases
Conditions
Keywords
colorectal cancer, liver metastases, liver transplant, non-resectable colorectal cancer metastases
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.
Interventions
PROCEDURELiver transplantation Ltx
Patients will be treated with Ltx at Sahlgrenska University Hospital, Göteborg, or Karolinska University Hospital, Huddinge.
OTHERBest alternative care
All available treatments as well as other experimental treatments are tolerated, however no cross-over to other arm will be allowed.
Sponsors
Vastra Gotaland Region
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 1. * 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 * Patient accepted for transplantation by a national study board * Signed and dated written informed consent before the start of specific protocol procedures.
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Five-year overall survival | randomization to follow up at 5 years | Percentage of subject who reach the endpoint of overall survival |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median overall survival | : Date of randomization until the date of death from any cause, assessed up to 5 years | Defined as time to death |
| 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 | Defined as time from randomization to progress of existing lesions, or appearance of new lesions, within the liver according to RECIST criteria (version 1.1) using CT or MRI and analysed using Kaplan-Meier and the log-rank test. |
| 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 | Defined as time from randomization to progress of existing lesions in the liver , or appearance of new lesions in the liver, according to RECIST criteria (version 1.1) using CT or MRI and analysed using Kaplan-Meier and the log-rank test. |
| Two-year overall survival | randomization to follow up at 2 years | Percentage of subject who reach the endpoint of overall survival |
| 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 | Assessed with EQ-5D-3L |
| Health economic evaluation | baseline, 3, 6, 12, 18, 24, 36 and 60 months | Estimation of Quality Adjusted Life Year (QALY) assessed with EQ-5D-3L |
| Extrahepatic recurrence-free survival | Date of randomization until the date of documented appearance of new extra-hepatic lesions, assessed up to 5 years | Defined as time from randomization to appearance of new extra-hepatic lesions, using CT or MRI and analysed using Kaplan-Meier and the log-rank test. |
Countries
Sweden
Outcome results
None listed