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

NCT ID: NCT02597348

Last Updated: 2024-02-14

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2026-07-31

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.

Conditions

Liver Metastasis; Colorectal Cancer; Metastasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Liver Transplantation

Arm LT+C: patients will be treated by experimental liver transplantation preceding the non experimental standard chemotherapy (according to usual practices).

Group Type: EXPERIMENTAL

Liver Transplantation

Intervention Type: PROCEDURE

The patient of the arm LT+C are treated by experimental liver transplantation preceding the Non experimental standard chemotherapy (according to usual practices) .

No intervention

Arm C: patients will receive non experimental standard chemotherapy according to usual practices in the context of definitively unresectable CLM.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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) .

Intervention Type: PROCEDURE

Other Intervention Names

Experimental LT+Non Experimental Usual Chimiotherapy

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)
• ≤ 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

René ADAM, PhD

Role: PRINCIPAL_INVESTIGATOR

AP-HP, Paul Brousse Hospital

Locations

AP-HP, Paul Brousse Hospital

Villejuif, , France

Countries

France

References

Adam R, Piedvache C, Chiche L, Adam JP, Salame E, Bucur P, Cherqui D, Scatton O, Granger V, Ducreux M, Cillo U, Cauchy F, Mabrut JY, Verslype C, Coubeau L, Hardwigsen J, Boleslawski E, Muscari F, Jeddou H, Pezet D, Heyd B, Lucidi V, Geboes K, Lerut J, Majno P, Grimaldi L, Levi F, Lewin M, Gelli M; Collaborative TransMet group. Liver transplantation plus chemotherapy versus chemotherapy alone in patients with permanently unresectable colorectal liver metastases (TransMet): results from a multicentre, open-label, prospective, randomised controlled trial. Lancet. 2024 Sep 21;404(10458):1107-1118. doi: 10.1016/S0140-6736(24)01595-2.

Reference Type: DERIVED

PMID: 39306468 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

P130922

Identifier Type: -

Identifier Source: org_study_id