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

Colorectal Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02597348
• Other study ID #: P130922
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 2016
• Est. completion date: July 2026

Study information

• Verified date: January 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 94
• Est. completion date: July 2026
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Liver Metastasis
• Liver Neoplasms
• Metastasis
• Neoplasm Metastasis
• Neoplasms, Second Primary

Intervention

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) .

Locations

Country	Name	City	State
France	AP-HP, Paul Brousse Hospital	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	5 years overall survival (OS)	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	3-years overall survival (OS)		3 years
Secondary	Disease free survival (DFS) (Arm LT+C) or Progression free survival (PFS) (Arm C)		3 and 5 years
Secondary	Recurrence rate at 3 and 5 years	Radiological assessment will be performed according to the RECIST criteria and confirmed by 2 local radiologists.	3 and 5 years
Secondary	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	year 5
Secondary	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	year 5
Secondary	Quality of life (QOL) of patients of Group LT followed by chemotherapy, using the NIDDK questionnaire of Liver Transplantation Database		year 5