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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Liver transplantation + best alternative care | Other | Patients subjected to Ltx will during the waiting time receive individualized chemotherapy, with the aim to avoid side effect that make them not transplantable. If possible, patients randomized to Ltx should be treated within 12 weeks after randomization. If the patients progress systemically they will be treated with best alternative care. If they progress only within the liver they continue to be transplantable until they are deemed technically not transplantable by the transplant surgeon. |
|
| Best alternative care | Other | The treating physician will together with the patient decide the treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Liver transplantation Ltx | Procedure | Patients will be treated with Ltx at Sahlgrenska University Hospital, Göteborg, or Karolinska University Hospital, Huddinge. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Five-year overall survival | Percentage of subject who reach the endpoint of overall survival | randomization to follow up at 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Two-year overall survival | Percentage of subject who reach the endpoint of overall survival | randomization to follow up at 2 years |
| Median overall survival | Defined as time to death |
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Inclusion Criteria:
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
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| Name | Affiliation | Role |
|---|---|---|
| Per G Lindner, MD, PhD | Transplant Institute, Sahlgrenska University Hospital | Principal Investigator |
| Carl Jorns, MD, PhD | Transplantation Unit, Karolinska University Hospital | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Transplant Institute, Sahlgrenska University Hospital | Gothenburg | Sweden | ||||
| Transplantation Unit, Karolinska University Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15166961 | Background | Abdalla EK, Vauthey JN, Ellis LM, Ellis V, Pollock R, Broglio KR, Hess K, Curley SA. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg. 2004 Jun;239(6):818-25; discussion 825-7. doi: 10.1097/01.sla.0000128305.90650.71. | |
| 23360920 |
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| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
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| Best alternative care | Other | All available treatments as well as other experimental treatments are tolerated, however no cross-over to other arm will be allowed. |
|
| : Date of randomization until the date of death from any cause, assessed up to 5 years |
| Progression-free survival | 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. | Date of randomization until the date of documented progression of existing lesions or appearance of new lesions, assessed up to 5 years |
| Hepatic progression-free survival | 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. | 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 |
| Extrahepatic recurrence-free survival | 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. | 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) | Assessed with EQ-5D-3L | baseline, 3, 6, 12, 18, 24, 36 and 60 months |
| Health economic evaluation | Estimation of Quality Adjusted Life Year (QALY) assessed with EQ-5D-3L | baseline, 3, 6, 12, 18, 24, 36 and 60 months |
| Stockholm |
| Sweden |
| Hagness M, Foss A, Line PD, Scholz T, Jorgensen PF, Fosby B, Boberg KM, Mathisen O, Gladhaug IP, Egge TS, Solberg S, Hausken J, Dueland S. Liver transplantation for nonresectable liver metastases from colorectal cancer. Ann Surg. 2013 May;257(5):800-6. doi: 10.1097/SLA.0b013e3182823957. |
| 24950280 | Background | Dueland S, Guren TK, Hagness M, Glimelius B, Line PD, Pfeiffer P, Foss A, Tveit KM. Chemotherapy or liver transplantation for nonresectable liver metastases from colorectal cancer? Ann Surg. 2015 May;261(5):956-60. doi: 10.1097/SLA.0000000000000786. |
| 29623268 | Background | Gorgen A, Muaddi H, Zhang W, McGilvray I, Gallinger S, Sapisochin G. The New Era of Transplant Oncology: Liver Transplantation for Nonresectable Colorectal Cancer Liver Metastases. Can J Gastroenterol Hepatol. 2018 Jan 10;2018:9531925. doi: 10.1155/2018/9531925. eCollection 2018. |
| 25959101 | Background | Fosby B, Melum E, Bjoro K, Bennet W, Rasmussen A, Andersen IM, Castedal M, Olausson M, Wibeck C, Gotlieb M, Gjertsen H, Toivonen L, Foss S, Makisalo H, Nordin A, Sanengen T, Bergquist A, Larsson ME, Soderdahl G, Nowak G, Boberg KM, Isoniemi H, Keiding S, Foss A, Line PD, Friman S, Schrumpf E, Ericzon BG, Hockerstedt K, Karlsen TH. Liver transplantation in the Nordic countries - An intention to treat and post-transplant analysis from The Nordic Liver Transplant Registry 1982-2013. Scand J Gastroenterol. 2015 Jun;50(6):797-808. doi: 10.3109/00365521.2015.1036359. |
| 36180944 | Derived | Reivell V, Hagman H, Haux J, Jorns C, Lindner P, Taflin H. SOULMATE: the Swedish study of liver transplantation for isolated colorectal cancer liver metastases not suitable for operation or ablation, compared to best established treatment-a randomized controlled multicenter trial. Trials. 2022 Sep 30;23(1):831. doi: 10.1186/s13063-022-06778-9. |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |