Liver Transplantation in Patients With Unresectable Colorectal Liver Metastases Treated by Chemotherapy (TRANSMET)

February 12, 2024 updated by: Assistance Publique - Hôpitaux de Paris

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

94

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Villejuif, France, 94800
        • AP-HP, Paul Brousse Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 performed in the 12 months prior to inclusion (except in case of primary tumor resection < 12 months )
  • 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)
  • ≤ 3 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Liver Transplantation
Arm LT+C: patients will be treated by experimental liver transplantation preceding the non experimental standard chemotherapy (according to usual practices).
Procedure: Liver Transplantation
The patient of the arm LT+C are treated by experimental liver transplantation preceding the Non experimental standard chemotherapy (according to usual practices) .
Other Names:
  • Experimental LT+Non Experimental Usual Chimiotherapy
No Intervention: No intervention
Arm C: patients will receive non experimental standard chemotherapy according to usual practices in the context of definitively unresectable CLM.

What is the study measuring?

Primary Outcome Measures

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

The evaluation of 5-years overall survival will be conducted by constructing survival curves using the Kaplan-Meier method. Graphs will be created following the best practices defined by Pocock.

  • If the proportionality of hazards is respected: Survival in each randomization arm will be compared using the Log-Rank test. The hazard ratio and the associated 95% confidence interval will be estimated using a Cox proportional hazards model.
  • If the proportionality of hazards is not respected: the difference in Restricted Mean Survival Time (RMST) between the arms and the associated 95% confidence interval will be estimated.

The randomization stratification by cluster of centers will not be taken into account in the analyses. This is because it was done for administrative reasons.
5 years

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: René ADAM, PhD, AP-HP, Paul Brousse Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2016

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

July 1, 2026

Study Registration Dates

First Submitted

October 23, 2015

First Submitted That Met QC Criteria

November 3, 2015

First Posted (Estimated)

November 5, 2015

Study Record Updates

Last Update Posted (Actual)

February 14, 2024

Last Update Submitted That Met QC Criteria

February 12, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P130922

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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