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

NCT04161092 | Active Not Recruiting DMC

• 1 other identifier: SOULMATE
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

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.

Conditions

Colorectal Cancer; Liver Metastases; Colorectal Liver Metastases

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Five-year overall survival

  Percentage of subject who reach the endpoint of overall survival

  randomization to follow up at 5 years

Secondary Outcomes (7)

• Two-year overall survival

  randomization to follow up at 2 years

• Median overall survival

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

• 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

• 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

• Extrahepatic recurrence-free survival

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

Study Arms (2)

Liver transplantation + best alternative care

OTHER

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

Best alternative care

OTHER

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

Other: Best alternative care

Interventions

Liver transplantation Ltx PROCEDURE

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

Liver transplantation + best alternative care

Best alternative care OTHER

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

Best alternative care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.
• Patient accepted for transplantation by a national study board
• Signed and dated written informed consent before the start of specific protocol procedures.

You may not qualify if:

• 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.
• BRAF (a gene that encodes a protein called b-raf) mutation in primary tumour
• microsatellite instability (MSI-H) in primary tumour
• Previous organ transplantation

Sponsors & Collaborators

• Vastra Gotaland Region: lead

Study Sites (2)

Transplant Institute, Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Transplantation Unit, Karolinska University Hospital

Stockholm, Sweden

Location

Related Publications (6)

• 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.

  PMID: 15166961 BACKGROUND

• 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.

  PMID: 23360920 BACKGROUND

• 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.

  PMID: 24950280 BACKGROUND

• 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.

  PMID: 29623268 BACKGROUND

• 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.

  PMID: 25959101 BACKGROUND

• 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.

  PMID: 36180944 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Per G Lindner, MD, PhD

  Transplant Institute, Sahlgrenska University Hospital

  PRINCIPAL INVESTIGATOR

• Carl Jorns, MD, PhD

  Transplantation Unit, Karolinska University Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2019
• First Posted: November 13, 2019
• Study Start: December 1, 2020
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): June 1, 2030
• Last Updated: October 28, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2)