The Swedish Study of Liver Transplantation for Non-resectable Colorectal Cancer Metastases

Colorectal Cancer Clinical Trial

— SOULMATE  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04161092
• Other study ID #: SOULMATE
• Status: Recruiting
• Phase: N/A
• Start date: December 1, 2020
• Est. completion date: June 2030

Study information

• Verified date: December 2020
• Source: Vastra Gotaland Region
• Contact: Per G Lindnér, MD, PhD
• Phone: +46705548400
• Email: per.lindner[@]vgregion.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: June 2030
• Est. primary completion date: December 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Liver Metastases
• Colorectal Neoplasms
• Liver Metastases
• Liver Neoplasms
• Neoplasm Metastasis
• Neoplasms, Second Primary

Intervention

Procedure:
• Liver transplantation Ltx
Patients will be treated with Ltx at Sahlgrenska University Hospital, Göteborg, or Karolinska University Hospital, Huddinge.

Other:
• Best alternative care
All available treatments as well as other experimental treatments are tolerated, however no cross-over to other arm will be allowed.

Locations

Country	Name	City	State
Sweden	Transplant Institute, Sahlgrenska University Hospital	Gothenburg
Sweden	Transplantation Unit, Karolinska University Hospital	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Vastra Gotaland Region

Country where clinical trial is conducted

Sweden, 

References & Publications (5)

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. — View 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. — View Citation

Fosby B, Melum E, Bjøro 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, Höckerstedt 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. — View 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. Review. — View Citation

Hagness M, Foss A, Line PD, Scholz T, Jørgensen 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Five-year overall survival	Percentage of subject who reach the endpoint of overall survival	randomization to follow up at 5 years
Secondary	Two-year overall survival	Percentage of subject who reach the endpoint of overall survival	randomization to follow up at 2 years
Secondary	Median overall survival	Defined as time to death	: Date of randomization until the date of death from any cause, assessed up to 5 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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