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

Sponsor

Vastra Gotaland Region (Other)

Overall Status

Recruiting

CT.gov ID

NCT04161092

Collaborator

(none)

Enrollment

Locations

Arms

114

Anticipated Duration (Months)

22.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Liver Metastases Colorectal Liver Metastases	Procedure: Liver transplantation Ltx Other: Best alternative care	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 1, 2020

Anticipated Primary Completion Date :

Dec 1, 2029

Anticipated Study Completion Date :

Jun 1, 2030

Arms and Interventions

Arm	Intervention/Treatment
Other: Liver transplantation + best alternative care 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.	Procedure: Liver transplantation Ltx Patients will be treated with Ltx at Sahlgrenska University Hospital, Göteborg, or Karolinska University Hospital, Huddinge.
Other: Best alternative care The treating physician will together with the patient decide the treatment.	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.

Arm

Intervention/Treatment

Other: Liver transplantation + best alternative care

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.

Procedure: Liver transplantation Ltx

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

Other: Best alternative care

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

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.

Outcome Measures

Primary Outcome Measures

Five-year overall survival [randomization to follow up at 5 years]
Percentage of subject who reach the endpoint of overall survival

Secondary Outcome Measures

Two-year overall survival [randomization to follow up at 2 years]
Percentage of subject who reach the endpoint of overall survival
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.
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.
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Transplant Institute, Sahlgrenska University Hospital	Gothenburg		Sweden
2	Transplantation Unit, Karolinska University Hospital	Stockholm		Sweden

Sponsors and Collaborators

Vastra Gotaland Region

Investigators

Principal Investigator: Per G Lindner, MD, PhD, Transplant Institute, Sahlgrenska University Hospital
Study Director: Carl Jorns, MD, PhD, Transplantation Unit, Karolinska University Hospital