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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
Sponsored by
Vastra Gotaland Region
About
Eligibility
Locations
Arms
Outcomes
Full info

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

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

First Posted
October 31, 2019
Last Updated
January 4, 2021
Sponsor
Vastra Gotaland Region
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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
No
Studies a U.S. FDA-regulated Device Product
No
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
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.
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
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.
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
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.
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
No
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
Email
per.lindner@vgregion.se
First Name & Middle Initial & Last Name or Official Title & Degree
Helena Taflin
Phone
+46700824799
Email
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
Email
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
Email
carl.jorns@sll.se

12. IPD Sharing Statement

Plan to Share IPD
No
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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