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

NCT07607873 | Recruiting DMC

• 1 other identifier: 276671
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Colorectal Liver Metastases

Keywords

Liver Transplantation; Colorectal Liver Metastases; Conversion Therapy; Liver Resection; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Overall survival will be measured from the date of randomization to death from any cause and analyzed according to the intention-to-treat principle.

  3 years

Secondary Outcomes (3)

• Disease-Free Survival (DFS)

  Up to 3 years

• Perioperative Morbidity

  90 days after treatment

• Perioperative Mortality

  90 days after treatment

Study Arms (2)

Transplantation

EXPERIMENTAL

Participants randomized to this arm will undergo liver transplantation after successful conversion to resectability following systemic therapy. In case of disease progression during the waiting period, patients may receive additional systemic therapy and be re-evaluated for transplant eligibility. In case of loss of eligibility, the patient will undergo the best standard of care (including resection). Post-transplant management will follow standard institutional protocols, including immunosuppressive therapy and oncologic follow-up.

Procedure: Liver Transplantation

Resection

ACTIVE COMPARATOR

Participants randomized to this arm will undergo radical local treatment consisting of hepatic resection with or without ablative techniques after successful conversion to resectability following systemic therapy. The surgical approach will be determined based on tumor characteristics and institutional standards, with the goal of achieving complete tumor removal (R0 resection). Perioperative management and postoperative care will follow standard clinical practice

Procedure: Liver Resection plus Ablation

Interventions

Liver Transplantation PROCEDURE

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

Transplantation

Liver Resection plus Ablation PROCEDURE

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

Resection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• Niguarda Hospital: lead

Study Sites (1)

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

RECRUITING

MeSH Terms

Interventions

Liver Transplantation; Hepatectomy

Intervention Hierarchy (Ancestors)

Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Digestive System Surgical Procedures; Surgical Procedures, Operative; Organ Transplantation; Transplantation

Study Officials

• Stefano Di Sandro, MD

  ASST Grande Ospedale Metropolitano Niguarda

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stefano Di Sandro, MD

CONTACT

+39026444; stefano.disandro@ospedaleniguarda.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-center, prospective, randomized, open-label study with a parallel assignment design. Eligible patients with initially unresectable colorectal liver metastases who achieve conversion to resectability after systemic therapy are randomized in a 1:1 ratio to receive either liver transplantation or radical local treatment (hepatic resection with or without ablation). Outcomes are analyzed according to the intention-to-treat principle.

Study Record Dates

• First Submitted: May 14, 2026
• First Posted: May 26, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 15, 2029
• Study Completion (Estimated): June 15, 2031
• Last Updated: July 17, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE

Locations

IT (1)