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

NCT04161092

Description:

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.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: The Swedish Study of Liver Transplantation for Non-resectable Colorectal Cancer Metastases
  • 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 IDs

  • ORG STUDY ID: SOULMATE
  • NCT ID: NCT04161092

Conditions

  • Colorectal Cancer
  • Liver Metastases
  • Colorectal Liver Metastases

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Liver transplantation + best alternative careOtherPatients 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.
    Best alternative careOtherThe treating physician will together with the patient decide the treatment.

      Eligibility Criteria

              Inclusion Criteria:
      
                -  Patients with non-resectable, non-abatable 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.
      
                -  Pulmonary lesions: No more than 2 lesions smaller than 5 mm or 1 lesion larger than 5
                   mm without pathological signal on PET-Thorax are accepted.
      
                -  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
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Five-year overall survival
      Time Frame:randomization to follow up at 5 years
      Safety Issue:
      Description:Percentage of subject who reach the endpoint of overall survival

      Secondary Outcome Measures

      Measure:Two-year overall survival
      Time Frame:randomization to follow up at 2 years
      Safety Issue:
      Description:Percentage of subject who reach the endpoint of overall survival
      Measure:Median overall survival
      Time Frame:: Date of randomization until the date of death from any cause, assessed up to 5 years
      Safety Issue:
      Description:Defined as time to death
      Measure:Progression-free survival
      Time Frame:Date of randomization until the date of documented progression of existing lesions or appearance of new lesions, assessed up to 5 years
      Safety Issue:
      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.
      Measure:Hepatic progression-free survival
      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
      Safety Issue:
      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.
      Measure:Extrahepatic recurrence-free survival
      Time Frame:Date of randomization until the date of documented appearance of new extra-hepatic lesions, assessed up to 5 years
      Safety Issue:
      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.
      Measure:Changes in quality of Life assessed with Euroqol Group Questionaire 5D-3L (EQ-5D-3L)
      Time Frame:baseline, 3, 6, 12, 18, 24, 36 and 60 months
      Safety Issue:
      Description:Assessed with EQ-5D-3L
      Measure:Health economic evaluation
      Time Frame:baseline, 3, 6, 12, 18, 24, 36 and 60 months
      Safety Issue:
      Description:Estimation of Quality Adjusted Life Year (QALY) assessed with EQ-5D-3L

      Details

      Phase:Phase 3
      Primary Purpose:Interventional
      Overall Status:Not yet recruiting
      Lead Sponsor:Vastra Gotaland Region

      Trial Keywords

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

      Last Updated