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RECRUITING

NCT07607873

TRANsplantation vs reSECTion After Conversion Therapy for Initially Unresectable Colorectal Liver Metastases

Sponsor: Niguarda Hospital

View on ClinicalTrials.gov

Summary

The TRANSECT trial is a prospective randomized study designed to evaluate the role of liver transplantation (LT) versus radical local treatment (hepatic resection and/or ablation) in patients with initially unresectable colorectal liver metastases (CRLM) converted to resectability after conversion therapy. Liver metastases are the leading cause of mortality in colorectal cancer patients. Although hepatic resection combined with chemotherapy remains the standard curative-intent treatment, only a minority of patients are eligible for upfront surgery. Advances in modern conversion chemotherapy have substantially increased the proportion of patients who can subsequently undergo curative local treatment. However, liver resection after intensive chemotherapy is still associated with high rates of intrahepatic recurrence, risk of R1 resections, chemotherapy-induced liver injury, and the need for complex surgical procedures carrying considerable morbidity and mortality. In parallel, recent studies investigating LT for unresectable CRLM, including the TRANSMET trial, demonstrated highly promising oncological outcomes, with 5-year overall survival rates exceeding 50% in selected patients. Based on these findings, the TRANSECT trial hypothesizes that LT may represent a more effective therapeutic strategy also in patients initially deemed unresectable but subsequently converted to resectability, by completely removing the hepatic metastatic niche. TRANSECT is a single-center, randomized, open-label, proof-of-concept trial. Patients with liver-only CRLM initially assessed as unresectable by a dedicated multidisciplinary tumor board and subsequently converted to resectability after systemic therapy will be randomized to either LT or hepatic resection and/or ablation. The primary endpoint is 3-year intention-to-treat overall survival (OS). Secondary endpoints include perioperative morbidity and mortality, disease-free survival, treatment adherence, quality of life, and exploratory translational analyses including radiomics and circulating tumor DNA assessment. A total of 70 patients (35 per arm) will be enrolled, with an estimated overall study duration of 5 years. TRANSECT represents the first randomized trial directly comparing LT and liver-directed surgery in patients with initially unresectable CRLM converted to resectability after systemic therapy, with the aim of redefining curative treatment strategies in this selected patient population.

Official title: TRANsplantation vs reSECTion After Conversion Therapy for Initially Unresectable

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

Start Date

2026-06-01

Completion Date

2031-06-15

Last Updated

2026-07-17

Healthy Volunteers

Conditions

Colorectal Liver Metastases

Interventions

PROCEDURE

Liver Transplantation

Orthotopic liver transplantation performed in patients with colorectal liver metastases after successful conversion to resectability following systemic therapy. Eligibility for transplantation is confirmed through multidisciplinary evaluation and restaging. Patients continue systemic therapy after randomization until listing for transplantation or until the date of the procedure is established. Postoperative management includes standard immunosuppressive therapy and oncologic follow-up according to institutional protocols

PROCEDURE

Liver Resection plus Ablation

Liver resection with or without ablative techniques in patients with colorectal liver metastases after successful conversion to resectability following systemic therapy. Patients continue systemic therapy after randomization until the surgical procedure is performed, according to protocol. The surgical strategy is determined by a multidisciplinary team with the aim of achieving complete tumor removal (R0 resection). Perioperative and postoperative management follow standard institutional practice

Inclusion Criteria screening phase (before randomization): * Signed screening phase informed consent. * Age \>18. * Performance status score of Eastern Cooperative Oncology Group (PS-ECOG) 0-1 * Adequate organ functions. * Liver-limited Metastatic Disease Confirmed as Unresectable by Colorectal Oncology Multidisciplinary Tumor Board (MTB). * Histologically documented adenocarcinoma of the colon or intra-peritoneal rectum * Absence of extra-hepatic disease demonstrated by contrast-enhanced CT + MRI and, in clinically indicated (clinical suspicion or elevated biomarkers), FDG-PET. * No previous systemic treatment for unresectable disease. * No previous systemic treatment for primary tumor resection * Recurrence occurring beyond six months after completion of adjuvant treatment. * MMR proficient cancer (MSS) regardless of RAS mutational status, BRAF-WT except for BRAF V600E-mut treated and responding to anti-BRAF + cytotoxic therapy. Exclusion criteria: * Absolute contraindication to liver transplant. * Other malignancies in the previous 5 years excluding non melanoma skin-cancers or in situ disease. * Hereditary CRC syndromes including FAP and Lynch syndrome. * Previous extrahepatic metastatic localization or locoregional tumor recurrence. * Extra-peritoneal cancers. * BRAFV600E-mut patients non-responder to 1st line anti-BRAF + cytotoxic therapy (Elez et al NEJM 2025, ref. 8) Randomization inclusion criteria: * Signed randomization phase informed consent. * CEA \< 80 ng/ml or decrease in CEA level at least 50% from baseline (TRANSMET criteria (5)). * Conversion to resectability according to MTB discussion during first 6 months of induction chemotherapy. * Sustained objective response defined as stable disease (SD), partial response (PR) or complete response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria (19), under chemotherapy, for at least 3 months. * Surgical resection of the primary tumor with a high oncological standard, as outlined in The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Colon Cancer (20), ensuring safe margins of resection and adequate TNM staging. * Histologically confirmed primary tumor with achievement of R0 resection. * Three months interval from primary tumor resection to randomization in patients staged up to pT3b and pN1. * Only metachronous metastases are eligible in pT4a and/or pN2 primary. For pT4a tumors, a minimum disease-free interval of 6 months from primary tumor resection is required before randomization. * Absence of local recurrence and extra-hepatic disease demonstrated by contrast-enhanced CT + MRI and, in clinically indicated (clinical suspicion or elevated biomarkers), FDG-PET. * PS-ECOG 0-1. * Adequate organ functions.

Locations (1)

ASST Grande Ospedale Metropolitano Niguarda

Milan, Italy