Liver Transplantation for Non-resectable Colorectal Liver Metastases: Translational Research

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

35 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-01-01

Study Completion Date

2026-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The patients with non-resectable colorectal liver metastases (CRLM) have always being considered a particular subgroup of CRLM in which the therapeutic approach, is focused on strategies that allow a potential surgery like neoadjuvant systemic treatments. But, the underlying biology that causes this particular profile of spread in a proportion of patients that always recur and progress in the liver has not been properly characterized from a biological point of view. Unfortunately, these patients finally develop liver metastasis not amenable for local treatments and become refractory to systemic treatments even without developing extrahepatic liver metastases. As a result, liver transplantation (LT) is a potential for patients without extrahepatic involvement and nonresectable CRLM. There are several studies that aims to evaluate if LT increases overall survival compared to best alternative care. To our knowledge, none of these studies incorporate objectives focused on the underlying tumor biology of this particular population and the development of focused strategies including a dynamic disease monitoring and targeted treatments for this particular population.The METLIVER trial will permit to expand the genetic studies to the whole complexity of metastatic lesions and a more precise evaluation of their genetic heterogeneity. Moreover, it will help to precise the type of genetic analyses on liquid biopsies that can be designed for patients that will unfortunately relapse mostly with lung metastases after LT. Our proposal will maximize the opportunity to produce an unprecedented knowledge on CRLM evolution and will provide new opportunities for relapsed patients.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Liver Transplantation in Patients With Unresectable Colorectal Liver Metastases

NCT04616495

Colorectal Cancer Metastatic Liver Cancer Liver Metastases

RECRUITING

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

NCT02597348

Liver Metastasis Colorectal Cancer Metastasis

ACTIVE_NOT_RECRUITING NA

Colorectal Metastasis to Liver Extraction With Auxiliary Transplant and Delayed Resection

NCT06698146

Liver Transplant Surgery Colorectal Cancer Metastatic Colon Cancer Liver Metastases

RECRUITING

Living Donor Liver Transplant for Unresectable Colorectal Liver Metastases

NCT05248581

Colorectal Cancer Metastatic

RECRUITING

Liver Transplantation and Colorectal Cancer

NCT01479608

Colorectal Cancer Liver Metastasis

RECRUITING NA

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

A prospective multicenter Spanish clinical phase II trial is proposed. The study population will consist of male and female with non-resectable CRLM, who are 18 to 70 years old, inclusive, at the time of providing informed consent. Patients will be identified, treated and followed by the clinical investigators within the different centers included in the present study. Those patients deemed unresectable CRLM by consensus in multidisciplinary meeting will be pre-screened for eligibility to be included in the study. After receiving the corresponding chemotherapy and if the patient meets the inclusion criteria and none of the exclusion criteria will sign the informed consent and will be evaluated for liver transplantation according to institutional protocols at the transplant unit. Patients eligible for liver transplantation will continue chemotherapy until the time of an organ is available. However, patients receiving treatment with bevacizumab or aflibercept will discontinue this treatment at time of inclusion in waiting list. If there are no further contraindications at the time of transplantation, laparotomy including tumor staging will be performed and if there is no sign of extrahepatic disease, liver transplantation will continue according to institutional protocols. Participants will be followed for 5 years and monitored for safety, survival and disease recurrence.

Regarding the translational research:

* The metastatic liver removed on day of transplant will be analysed using high-throughput single-cell RNA sequencing (scRNA-seq) which will allow deep phenotyping of cells for detection of rare and common cell populations and determination of developmental trajectories of distinct cell lineages.
* RAS allele fraction will be monitored by BEAMing and it will be performed before chemotherapy treatment, before LT, post-transplantation, and every 3 months until the patient relapses if relapses.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Colorectal Cancer Liver Metastases Genetic Change

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Transplantation

Liver transplantation for the treatment of unresectable colorectal cancer liver metastases

Group Type EXPERIMENTAL

Liver transplantation

Intervention Type OTHER

Liver transplantation

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Liver transplantation

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Willing and able to provide written informed consent.
2. Male or female, aged 18-70 years old inclusive at study entry.
3. ECOG (Eastern Cooperative Oncology Group) 0 or 1.
4. Histologically-proven primary colorectal tumor.
5. Bilateral, limited at liver and non-resectable CRLM by consensus in Multidisciplinary Committee.
6. Resection of primary colorectal tumor according oncological principles and adequate TNM stage.
7. Time from primary colorectal tumor resection to transplant ≥ 12 months.
8. Primary colorectal tumor stage ≤ T3N1. If time between primary tumor resection is ≥ 2 years, stage T4N0 or T4N2 is accepted.
9. No signs of extrahepatic metastatic disease according to PET/CT scan, CT and pelvic MRI.
10. The patient has undergone systemic chemotherapy for a minimum of 3 months at the time of screening and maximum of 2 lines of fluoropyrimidine based chemotherapy combined or not with irinotecan or oxaliplatin associated or no not with targeted therapy based in molecular biomarkers.
11. Demonstrated stability or partial regression of CRLM following RECIST criteria v 1.1., at minimum 3 months since the last treatment received and immediately prior to screening.
12. CEA (Carcinoembryonic antigen) values ≤ 80 µg/L immediately prior to screening.
13. Adequate blood test regarding:

* Creatinine ≤1.25 x upper normal level or estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73m2 using following the Chronic Kidney disease epidemiology collaboration (CKD-EPI) formula.
* Platelets ≥80 × 109/L
* Neutrophiles ≥ 2.5 × 109/L

Exclusion Criteria

1. Largest Lesion \>5.5cm immediately prior to screening
2. Patients with Lynch Syndrome
3. BRAF mutation and/or primary tumor of microsatellite instability (MSI)
4. Recurrence of primary tumor confirmed by colonoscopy or pelvic MRI within the last 12 months prior to screening.
5. Previous or concurrent cancer in the last 5 years. Any cancer curatively treated 5 years prior to entry or treated basal cell carcinoma is permitted.
6. Substance abuse, medical, psychological or social conditions that may interfere with the patient´s participation in the study or evaluation of the study results.
7. Cardiac or pulmonary disease uncontrolled as contraindication for any surgical procedure.
8. Active infection.
9. Pregnant or breast-feeding patients
10. Any reason why in the opinion of the investigator, the patient should not participate.

Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Cristina Dopazo Taboada

Consultant surgeon, MD/PhD

Responsibility Role PRINCIPAL_INVESTIGATOR