Clinical trial NCT04161092: The Swedish Study of Liver Transplantation for Non-resectable Colorectal Cancer Metastases
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Colorectal Cancer
Liver Metastases
Colorectal Liver Metastases
Keywords: colorectal cancer
liver metastases
liver transplant
non-resectable colorectal cancer metastases
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
First posted: 2019-11-13
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 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

Primary outcomes:
measure: Five-year overall survival
timeFrame: randomization to follow up at 5 years
Secondary outcomes:
measure: Two-year overall survival
timeFrame: randomization to follow up at 2 years
measure: Median overall survival
timeFrame: : Date of randomization until the date of death from any cause, assessed up to 5 years
measure: Progression-free survival
timeFrame: Date of randomization until the date of documented progression of existing lesions or appearance of new lesions, assessed up to 5 years
measure: Hepatic progression-free survival
timeFrame: 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
measure: Extrahepatic recurrence-free survival
timeFrame: Date of randomization until the date of documented appearance of new extra-hepatic lesions, assessed up to 5 years
measure: Changes in quality of Life assessed with Euroqol Group Questionaire 5D-3L (EQ-5D-3L)
timeFrame: baseline, 3, 6, 12, 18, 24, 36 and 60 months
measure: Health economic evaluation
timeFrame: baseline, 3, 6, 12, 18, 24, 36 and 60 months
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Transplant Institute, Sahlgrenska University Hospital
city: Stockholm
country: Sweden
facility: Transplantation Unit, Karolinska University Hospital
Study officials:
affiliation: Transplant Institute, Sahlgrenska University Hospital
name: Per G Lindner, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Transplantation Unit, Karolinska University Hospital
name: Carl Jorns, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.