Back to resultsLiver Transplantation in Patients With Unresectable Colorectal Liver Metastases Treated by Chemotherapy (TRANSMET)
Primary Purpose
Liver Metastasis, Colorectal Cancer, Metastasis
Status
Active
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Liver Transplantation
Sponsored by
About this trial
This is an interventional treatment trial for Liver Metastasis focused on measuring Liver, Metastasis, Colorectal cancer, Liver transplantation
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 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)
- ≤ 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
Sites / Locations
- AP-HP, Paul Brousse Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Liver Transplantation
No intervention
Arm Description
Arm LT+C: patients will be treated by experimental liver transplantation preceding the non experimental standard chemotherapy (according to usual practices).
Arm C: patients will receive non experimental standard chemotherapy according to usual practices in the context of definitively unresectable CLM.
Outcomes
Primary Outcome Measures
5 years overall survival (OS)
Secondary Outcome Measures
3-years overall survival (OS)
Disease free survival (DFS) (Arm LT+C) or Progression free survival (PFS) (Arm C)
Recurrence rate at 3 and 5 years
Radiological assessment will be performed according to the RECIST criteria and confirmed by 2 local radiologists.
Quality of life (QOL) of patients using the European Organization for Research and Treatment of Cancer (EORTC) questionnaires.: QLQ-C30
QLQ-C30 covers general aspects of health-related quality of life
Quality of life (QOL) of patients using the European Organization for Research and Treatment of Cancer (EORTC) questionnaires.: QLQ-LMC21
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
Quality of life (QOL) of patients of Group LT followed by chemotherapy, using the NIDDK questionnaire of Liver Transplantation Database
Full Information
NCT ID
NCT02597348
First Posted
October 23, 2015
Last Updated
July 31, 2021
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT02597348
Brief Title
Liver Transplantation in Patients With Unresectable Colorectal Liver Metastases Treated by Chemotherapy
Acronym
TRANSMET
Official Title
Curative Potential of Liver Transplantation in Patients With Definitively Unresectable Colorectal Liver Metastases (CLM) Treated by Chemotherapy: a Prospective Multicentric Randomized Trial
Study Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 2016 (Actual)
Primary Completion Date
July 2026 (Anticipated)
Study Completion Date
July 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Metastasis, Colorectal Cancer, Metastasis
Keywords
Liver, Metastasis, Colorectal cancer, Liver transplantation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
94 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Liver Transplantation
Arm Type
Experimental
Arm Description
Arm LT+C: patients will be treated by experimental liver transplantation preceding the non experimental standard chemotherapy (according to usual practices).
Arm Title
No intervention
Arm Type
No Intervention
Arm Description
Arm C: patients will receive non experimental standard chemotherapy according to usual practices in the context of definitively unresectable CLM.
Intervention Type
Procedure
Intervention Name(s)
Liver Transplantation
Other Intervention Name(s)
Experimental LT+Non Experimental Usual Chimiotherapy
Intervention Description
The patient of the arm LT+C are treated by experimental liver transplantation preceding the Non experimental standard chemotherapy (according to usual practices) .
Primary Outcome Measure Information:
Title
5 years overall survival (OS)
Time Frame
5 years
Secondary Outcome Measure Information:
Title
3-years overall survival (OS)
Time Frame
3 years
Title
Disease free survival (DFS) (Arm LT+C) or Progression free survival (PFS) (Arm C)
Time Frame
3 and 5 years
Title
Recurrence rate at 3 and 5 years
Description
Radiological assessment will be performed according to the RECIST criteria and confirmed by 2 local radiologists.
Time Frame
3 and 5 years
Title
Quality of life (QOL) of patients using the European Organization for Research and Treatment of Cancer (EORTC) questionnaires.: QLQ-C30
Description
QLQ-C30 covers general aspects of health-related quality of life
Time Frame
year 5
Title
Quality of life (QOL) of patients using the European Organization for Research and Treatment of Cancer (EORTC) questionnaires.: QLQ-LMC21
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
Time Frame
year 5
Title
Quality of life (QOL) of patients of Group LT followed by chemotherapy, using the NIDDK questionnaire of Liver Transplantation Database
Time Frame
year 5
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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 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)
≤ 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
René ADAM, PhD
Organizational Affiliation
AP-HP, Paul Brousse Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
AP-HP, Paul Brousse Hospital
City
Villejuif
ZIP/Postal Code
94800
Country
France
12. IPD Sharing Statement
Learn more about this trial
Liver Transplantation in Patients With Unresectable Colorectal Liver Metastases Treated by Chemotherapy
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