TRANsplantation vs reSECTion After Conversion Therapy for Initially Unresectable
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 1
研究概览
简要总结
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.
详细描述
Liver metastases represent the leading cause of mortality in patients with colorectal cancer. Although hepatic resection combined with systemic therapy remains the standard curative-intent treatment, a substantial proportion of patients present with disease that is initially unresectable at diagnosis.
Over the last years, advances in systemic chemotherapy and targeted therapies have significantly increased conversion-to-resectability rates in patients with initially unresectable colorectal liver metastases. As systemic therapies continue to improve, the number of patients achieving conversion from initially unresectable to potentially resectable disease is expected to progressively increase, making this clinical scenario increasingly relevant in daily practice.
However, surgical treatment after conversion therapy remains associated with important oncological and surgical challenges. A complete radiological response does not necessarily correspond to a complete pathological response, with the possible persistence of microscopic residual disease and a consequent risk of intrahepatic recurrence. In addition, prolonged exposure to chemotherapy may result in liver toxicity and impairment of the residual liver parenchyma, increasing the complexity of surgical strategies required to achieve radical resection and raising the risk of post-hepatectomy liver failure.
In this context, liver transplantation may represent an alternative therapeutic strategy that could overcome some of the limitations of resective surgery by completely replacing the metastatic liver and eradicating both macroscopic and microscopic residual disease.
This is a single-center, prospective, randomized, open-label, proof-of-concept study designed to compare liver transplantation with radical local treatment in patients with colorectal liver metastases initially unresectable and subsequently converted to resectability following systemic therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •screening phase (before randomization):
- •Signed screening phase informed consent.
- •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.
排除标准
- •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 pN
- •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-
- •Adequate organ functions.
研究组 & 干预措施
Transplantation
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.
干预措施: Liver Transplantation (Procedure)
Resection
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
干预措施: Liver Resection plus Ablation (Procedure)