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

Primary Purpose

Colorectal Cancer, Liver Metastases, Colorectal Liver Metastases

Status

Recruiting

Phase

Not Applicable

Locations

Sweden

Study Type

Interventional

Intervention

Liver transplantation Ltx

Best alternative care

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring colorectal cancer, liver metastases, liver transplant, non-resectable colorectal cancer metastases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Transplant Institute, Sahlgrenska University HospitalRecruiting
Transplantation Unit, Karolinska University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

Liver transplantation + best alternative care

Best alternative care

Arm Description

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.

The treating physician will together with the patient decide the treatment.

Outcomes

Primary Outcome Measures

Five-year overall survival

Percentage of subject who reach the endpoint of overall survival

Secondary Outcome Measures

Two-year overall survival

Percentage of subject who reach the endpoint of overall survival

Median overall survival

Defined as time to death

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.

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.

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.

Changes in quality of Life assessed with Euroqol Group Questionaire 5D-3L (EQ-5D-3L)

Assessed with EQ-5D-3L

Health economic evaluation

Estimation of Quality Adjusted Life Year (QALY) assessed with EQ-5D-3L

Full Information

NCT ID

NCT04161092

First Posted

October 31, 2019

Last Updated

January 4, 2021

Sponsor

Vastra Gotaland Region

1. Study Identification

Unique Protocol Identification Number

NCT04161092

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Recruiting

Study Start Date

December 1, 2020 (Actual)

Primary Completion Date

December 2029 (Anticipated)

Study Completion Date

June 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Vastra Gotaland Region

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer, Liver Metastases, Colorectal Liver Metastases

Keywords

colorectal cancer, liver metastases, liver transplant, non-resectable colorectal cancer metastases

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Liver transplantation + best alternative care

Arm Type

Other

Arm Description

Arm Title

Best alternative care

Arm Type

Other

Arm Description

The treating physician will together with the patient decide the treatment.

Intervention Type

Procedure

Intervention Name(s)

Liver transplantation Ltx

Intervention Description

Patients will be treated with Ltx at Sahlgrenska University Hospital, Göteborg, or Karolinska University Hospital, Huddinge.

Intervention Type

Other

Intervention Name(s)

Best alternative care

Intervention Description

All available treatments as well as other experimental treatments are tolerated, however no cross-over to other arm will be allowed.

Primary Outcome Measure Information:

Title

Five-year overall survival

Description

Percentage of subject who reach the endpoint of overall survival

Time Frame

randomization to follow up at 5 years

Secondary Outcome Measure Information:

Title

Two-year overall survival

Description

Percentage of subject who reach the endpoint of overall survival

Time Frame

randomization to follow up at 2 years

Title

Median overall survival

Description

Defined as time to death

Time Frame

: Date of randomization until the date of death from any cause, assessed up to 5 years

Title

Progression-free survival

Description

Time Frame

Date of randomization until the date of documented progression of existing lesions or appearance of new lesions, assessed up to 5 years

Title

Hepatic progression-free survival

Description

Time Frame

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

Title

Extrahepatic recurrence-free survival

Description

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.

Time Frame

Date of randomization until the date of documented appearance of new extra-hepatic lesions, assessed up to 5 years

Title

Changes in quality of Life assessed with Euroqol Group Questionaire 5D-3L (EQ-5D-3L)

Description

Assessed with EQ-5D-3L

Time Frame

baseline, 3, 6, 12, 18, 24, 36 and 60 months

Title

Health economic evaluation

Description

Estimation of Quality Adjusted Life Year (QALY) assessed with EQ-5D-3L

Time Frame

baseline, 3, 6, 12, 18, 24, 36 and 60 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Per G Lindnér, MD, PhD

Phone

+46705548400

per.lindner@vgregion.se

First Name & Middle Initial & Last Name or Official Title & Degree

Helena Taflin

Phone

+46700824799

helena.taflin@vgregion.se

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Per G Lindner, MD, PhD

Organizational Affiliation

Transplant Institute, Sahlgrenska University Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Carl Jorns, MD, PhD

Organizational Affiliation

Transplantation Unit, Karolinska University Hospital

Official's Role

Study Director

Facility Information:

Facility Name

Transplant Institute, Sahlgrenska University Hospital

City

Gothenburg

Country

Sweden

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Veronica Reivell

Phone

+46705129087

veronica.reivell@vgregion.se

Facility Name

Transplantation Unit, Karolinska University Hospital

City

Stockholm

Country

Sweden

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Carl Jorns, MD, PhD

Phone

+46762721845

carl.jorns@sll.se

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

15166961

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.

Results Reference

background

PubMed Identifier

23360920

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.

Results Reference

background

PubMed Identifier

24950280

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.

Results Reference

background

PubMed Identifier

29623268

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.

Results Reference

background

PubMed Identifier

25959101

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.

Results Reference

background

PubMed Identifier

36180944

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.

Results Reference

derived

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

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