Clinical Trials /

Liver Transplantation in Patients With Unresectable Colorectal Liver Metastases Treated by Chemotherapy

NCT02597348

Description:

This is a multicentric randomized parallel group open trial comparing 5-year survival of chemotherapy followed by LT (Group LT+C) versus chemotherapy alone (Group C) in patients with confirmed unresectable liver-only metastases, well controlled by chemotherapy (no progression) and extensively explored by modern imaging techniques. The primary objective of the trial is to validate in a large multicentric cohort of selected patients the possibility to obtain at least 50% 5-years survival with LT combined to chemotherapy compared to around 10% with chemotherapy alone.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Liver Transplantation in Patients With Unresectable Colorectal Liver Metastases Treated by Chemotherapy
  • Official Title: Curative Potential of Liver Transplantation in Patients With Definitively Unresectable Colorectal Liver Metastases (CLM) Treated by Chemotherapy: a Prospective Multicentric Randomized Trial

Clinical Trial IDs

  • ORG STUDY ID: P130922
  • NCT ID: NCT02597348

Conditions

  • Liver Metastasis
  • Colorectal Cancer
  • Metastasis

Purpose

This is a multicentric randomized parallel group open trial comparing 5-year survival of chemotherapy followed by LT (Group LT+C) versus chemotherapy alone (Group C) in patients with confirmed unresectable liver-only metastases, well controlled by chemotherapy (no progression) and extensively explored by modern imaging techniques. The primary objective of the trial is to validate in a large multicentric cohort of selected patients the possibility to obtain at least 50% 5-years survival with LT combined to chemotherapy compared to around 10% with chemotherapy alone.

Detailed Description

      Liver transplantation (LT) has recently been proposed as alternative treatment for
      definitively unresectable colorectal liver metastases in selected patients with a 60%
      estimated survival at 5 years in a recent prospective Norwegian study. However, disease free
      survival (DFS) in this preliminary study has been poor with 90% of recurrence after LT.

      The objective of our study is to validate LT as a therapeutic option on a large multicentric
      scale throughout a highly strict policy selection in term of survival, disease free survival
      and quality of life. In order to reduce selection bias, unresectability criteria and
      theorical indication to LT will be confirmed by an independent Steering Committee including
      HPB surgeons, oncologists, radiologists and hepatologists.
    

Trial Arms

NameTypeDescriptionInterventions
Liver TransplantationExperimentalArm LT+C: patients will be treated by experimental liver transplantation preceding the non experimental standard chemotherapy (according to usual practices).
    No interventionNo InterventionArm C: patients will receive non experimental standard chemotherapy according to usual practices in the context of definitively unresectable CLM.

      Eligibility Criteria

              Inclusion Criteria:
      
                -  ≥ 18 and ≤ 65 years
      
                -  Good performance status, ECOG 0 or 1 (39).
      
                -  Histologically proved adenocarcinoma in colon or rectum
      
                -  BRAF wild-type CRC on primary tumor or liver metastases
      
                -  High standard oncological surgical resection of the primary defined by :
      
                     -  Safe margin of resection
      
                     -  Curative resection of primary tumor according to oncological principles
      
                     -  TNM adequate staging
      
                -  Absence of local recurrence on colonoscopy (within 12 months before inclusion)
      
                -  Confirmed non resectable colorectal liver metastases by the validation committee
      
                -  ≥ 3 months of tumor control during the last chemotherapy line: Stable or Partial
                   Response on RECIST criteria (40)
      
                -  ≤ 2 lines of chemotherapy for metastatic disease
      
                -  CEA < 80 microg/L or a decrease ≥ 50% of the highest serum CEA levels observed during
                   the disease
      
                -  Absence of extrahepatic tumor localisation according to CT scan and PET-CT
      
                -  Renal function should be within the normal limits
      
                -  No need for extra-renal purification procedure, hemodialysis or kidney transplantation
                   associated (nephrologist assessment)
      
                -  A platelet count> 80,000 / mm3
      
                -  White blood cell count> 2500 / mm3
      
                -  Eligible for both treatments groups
      
                -  Signed informed consent and expected cooperation of the patient for the treatment and
                   follow up
      
              Exclusion Criteria:
      
                -  Participation refusal
      
                -  No health insurance facilities
      
                -  General contraindication to LT (Severe cardiopulmonary disease or other life-limiting
                   coexisting medical conditions, extrahepatic malignancy, active alcohol or substance
                   abuse, active infection or uncontrolled sepsis, lack of psychosocial support or
                   inability to comply with medical treatment)
      
                -  Other malignancies either concomitant or within 5 years before liver transplantation
      
                -  Patients not having received standard treatment for the primary CRC according to
                   recommended guidelines
      
                -  Prior extra hepatic metastatic disease or local relapse
      
                -  Pregnancy at the time of inclusion
            
      Maximum Eligible Age:65 Years
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:5 years overall survival (OS)
      Time Frame:5 years
      Safety Issue:
      Description:

      Secondary Outcome Measures

      Measure:3-years overall survival (OS)
      Time Frame:3 years
      Safety Issue:
      Description:
      Measure:Disease free survival (DFS) (Arm LT+C) or Progression free survival (PFS) (Arm C)
      Time Frame:3 and 5 years
      Safety Issue:
      Description:
      Measure:Recurrence rate at 3 and 5 years
      Time Frame:3 and 5 years
      Safety Issue:
      Description:Radiological assessment will be performed according to the RECIST criteria and confirmed by 2 local radiologists.
      Measure:Quality of life (QOL) of patients using the European Organization for Research and Treatment of Cancer (EORTC) questionnaires.: QLQ-C30
      Time Frame:year 5
      Safety Issue:
      Description:QLQ-C30 covers general aspects of health-related quality of life
      Measure:Quality of life (QOL) of patients using the European Organization for Research and Treatment of Cancer (EORTC) questionnaires.: QLQ-LMC21
      Time Frame:year 5
      Safety Issue:
      Description:QLQ-LMC21 is valid and reliable questionnaire module to use with the QLQ-C30 in assessing in hepatectomy or palliative treatment for colorectal liver metastases
      Measure:Quality of life (QOL) of patients of Group LT followed by chemotherapy, using the NIDDK questionnaire of Liver Transplantation Database
      Time Frame:year 5
      Safety Issue:
      Description:

      Details

      Phase:Phase 3
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Assistance Publique - Hôpitaux de Paris

      Trial Keywords

      • Liver
      • Metastasis
      • Colorectal cancer
      • Liver transplantation

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