Clinical Trials /

Living Donor Liver Transplantation for Unresectable Colorectal Cancer Liver Metastases

NCT02864485

Description:

Patients with unresectable liver metastases (LM) from colorectal cancer (CRC)have a poor prognosis. In patients with resectable disease, surgery offers a distinct survival benefit. This study will offer live donor liver transplantation (LDLT) to select patients with unresectable metastases that are 1) limited to the liver and 2) stable (non-progressing) on standard chemotherapy. Potential participants will be evaluated for liver transplant suitability and must also have a willing, healthy living donor come forward for evaluation. Those participants who undergo LDLT will be followed for survival, disease-free survival and quality of life for 5 years and compared to a "control group" of participants who drop out of study prior to transplantation due to reasons other than cancer progression.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Living Donor Liver Transplantation for Unresectable Colorectal Cancer Liver Metastases
  • Official Title: Assessment of a Protocol Using a Combination of Neo-adjuvant Chemotherapy Plus Living Donor Liver Transplantation for Non-Resectable Liver Metastases From Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: 15-9382-C
  • NCT ID: NCT02864485

Conditions

  • Colorectal Cancer
  • Liver Metastases

Purpose

Patients with unresectable liver metastases (LM) from colorectal cancer (CRC)have a poor prognosis. In patients with resectable disease, surgery offers a distinct survival benefit. This study will offer live donor liver transplantation (LDLT) to select patients with unresectable metastases that are 1) limited to the liver and 2) stable (non-progressing) on standard chemotherapy. Potential participants will be evaluated for liver transplant suitability and must also have a willing, healthy living donor come forward for evaluation. Those participants who undergo LDLT will be followed for survival, disease-free survival and quality of life for 5 years and compared to a "control group" of participants who drop out of study prior to transplantation due to reasons other than cancer progression.

Detailed Description

      Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide.
      Approximately half of all patients develop metastases, often to the liver or lung. Surgical
      treatment of liver metastases (LM) is the only curative treatment option; however, it has
      been estimated that only 20-40% of patients are candidates for liver resection. Surgery
      offers a distinct survival advantage: the 5-year survival after liver resection for LM is
      around 40-50% in most studies versus 10-20% 5-year survival for chemotherapy alone.

      In cases where the colorectal metastases are isolated to the liver but "unresectable", the
      total hepatectomy resulting from liver transplantation would remove all evident disease. CRC
      LM are considered an absolute contraindication for liver transplantation (LT) at most centers
      but recent reports of LT for colorectal LM from a single center in Oslo, Norway demonstrated
      a 5-year survival of 56%. The Norway study was not stringent about inclusion criteria or
      pre-transplant chemotherapy, and transplanted patients whose tumors were actively growing. As
      a result many participants developed disease recurrence quite rapidly following transplant.
      The investigators hypothesize that tighter criteria would result in improved outcomes.

      Unfortunately, with a lack of deceased donor grafts for the investigators existing transplant
      patients, the investigators cannot utilize decease donor grafts for this study. Therefore the
      investigators will explore Living Donor Liver Transplantation (LDLT). Furthermore, LDLT is an
      elective surgery, allowing for more control over pre-transplant chemotherapy and tumor
      monitoring. This study will offer live donor liver transplantation (LDLT) to select patients
      with unresectable metastases that are 1) limited to the liver and 2) stable (non-progressing)
      on standard chemotherapy. Potential participants will be evaluated for liver transplant
      suitability and must also have a willing, healthy living donor come forward for evaluation.
      Those participants who undergo LDLT will be followed for survival, disease-free survival and
      quality of life for 5 years and compared to a "control group" of participants who drop out of
      study prior to transplantation due to reasons other than cancer progression.
    

Trial Arms

NameTypeDescriptionInterventions
transplantationExperimentalLive donor liver transplantation for the treatment of unresectable colorectal cancer liver metastases

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Must reside in Canada
    
              -  ECOG ( Eastern Cooperative Oncology Group) score : 0-1 at all times prior to LDLT
                 (excursions to ECOG 2 allowed at investigator's discretion)
    
              -  Proven colorectal Liver Metastases (LM).
    
              -  Willing and able to provide written informed consent.
    
              -  Negative serum pregnancy test for women of childbearing potential
    
              -  Both men and women must agree to use adequate barrier birth control measures during
                 the course of the trial.
    
              -  At least 1 "acceptable", ABO-compatible living donor has stepped forward
    
              -  Primary Colorectal cancer tumor stage is ≤T4a
    
              -  Time from primary CRC resection to transplant is ≥6 months
    
              -  Bilateral and non-resectable LM
    
              -  No major vascular invasion by LM; metastases isolated to liver
    
              -  The patient has undergone systemic chemotherapy (eg. FOLFOX +/- bevacizumab or FOLFIRI
                 +/- bevacizumab) for ≥3 months
    
              -  demonstrated stability or regression of LM over at minimum the 3 months preceding
                 screening
    
              -  Carcinoembryonic Antigen (CEA) values are stable or decreasing at all timepoints prior
                 to the transplant surgery.
    
            Exclusion Criteria:
    
              -  Previous or concurrent cancer (with some exceptions)
    
              -  prior liver resection (performed with curative intent) where current LM represent
                 recurrent disease.
    
              -  prior lung resection
    
              -  Progression of LM at any timepoint prior to transplant surgery
    
              -  Renal dysfunction with an estimated creatinine clearance of less than 50 ml/min
    
              -  Pulmonary insufficiency
    
              -  History of cardiac disease
    
              -  Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B
                 and/or C infection.
    
              -  Patients with debilitating neuropathy. (CTCAE > grade 2)
    
              -  BRAF + tumors
    
              -  Any condition that is unstable or which could jeopardize the safety of the patient and
                 his/her compliance in the study
          
    Maximum Eligible Age:65 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:patient survival
    Time Frame:5 years
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:patterns of cancer recurrence after liver transplantation
    Time Frame:5 years
    Safety Issue:
    Description:
    Measure:types of cancer recurrence treatments
    Time Frame:5 years
    Safety Issue:
    Description:
    Measure:Number of participants that drop out of study prior to receiving intervention (transplantation surgery) due to chemotherapy-related adverse events, as assessed by CTCAE v4.0
    Time Frame:prior to liver transplantation
    Safety Issue:
    Description:
    Measure:self-reported quality of life as assessed by EORTC QLQ-C30 questionnaire
    Time Frame:6 month intervals for 5 years
    Safety Issue:
    Description:Compare the QoL of participants undergoing intervention vs participants that drop-out (for non cancer related reasons and are thereafter receiving palliative chemotherapy)
    Measure:survival of intervention vs standard treatment
    Time Frame:1-, 3- and 5 years
    Safety Issue:
    Description:Compare the 1-, 3- and 5- year survival of patients that undergo intervention with those that drop-out of the study (due to non-cancer related reasons and receive standard chemotherapy)
    Measure:patient survival
    Time Frame:1 year
    Safety Issue:
    Description:
    Measure:patient survival
    Time Frame:3 years
    Safety Issue:
    Description:
    Measure:disease-free survival
    Time Frame:1 year
    Safety Issue:
    Description:
    Measure:disease-free survival
    Time Frame:3 years
    Safety Issue:
    Description:

    Details

    Phase:N/A
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:University Health Network, Toronto

    Trial Keywords

    • Live donor liver transplantation

    Last Updated