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

NCT05398380 | Recruiting

• 1 other identifier: METLIVER Study
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Cancer; Liver Metastases; Genetic Change

Keywords

Liver Transplantation; Non-resectable colorectal liver metastases; Tumoral biomarkers; Translational research

Outcome Measures

Primary Outcomes (1)

• Five years overall survival

  Percentage of subject who reach the endpoint of overall survival from the inclusion in waiting list until death or last follow-up

  5 years

Secondary Outcomes (5)

• One and three years overall survival

  1 and 3 years

• One, three and five years recurrence free survival

  1, 3 and 5 years

• Number of patients that drop-out of the study prior to receive intervention

  Prior to liver transplantation

• Patterns of cancer recurrence after liver transplantation

  5 years

• Changes in quality of life assessed by EORTC QLQ-C30 questionnaire (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30)

  5 years

Other Outcomes (2)

• Percentage of the intratumoral genetic heterogeneity of the metastatic liver through an in-depth lineage study

  On day of transplantation

• Percentage of patients with circulating tumor DNA (ctDNA)

  5 years

Study Arms (1)

Transplantation

EXPERIMENTAL

Liver transplantation for the treatment of unresectable colorectal cancer liver metastases

Other: Liver transplantation

Interventions

Liver transplantation OTHER

Liver transplantation

Transplantation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent.
• Male or female, aged 18-70 years old inclusive at study entry.
• ECOG (Eastern Cooperative Oncology Group) 0 or 1.
• Histologically-proven primary colorectal tumor.
• Bilateral, limited at liver and non-resectable CRLM by consensus in Multidisciplinary Committee.
• Resection of primary colorectal tumor according oncological principles and adequate TNM stage.
• Time from primary colorectal tumor resection to transplant ≥ 12 months.
• Primary colorectal tumor stage ≤ T3N1. If time between primary tumor resection is ≥ 2 years, stage T4N0 or T4N2 is accepted.
• No signs of extrahepatic metastatic disease according to PET/CT scan, CT and pelvic MRI.
• 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.
• 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.
• CEA (Carcinoembryonic antigen) values ≤ 80 µg/L immediately prior to screening.
• 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

You may not qualify if:

• Largest Lesion \>5.5cm immediately prior to screening
• Patients with Lynch Syndrome
• BRAF mutation and/or primary tumor of microsatellite instability (MSI)
• Recurrence of primary tumor confirmed by colonoscopy or pelvic MRI within the last 12 months prior to screening.
• 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.
• Substance abuse, medical, psychological or social conditions that may interfere with the patient´s participation in the study or evaluation of the study results.
• Cardiac or pulmonary disease uncontrolled as contraindication for any surgical procedure.
• Active infection.
• Pregnant or breast-feeding patients
• Any reason why in the opinion of the investigator, the patient should not participate.

Sponsors & Collaborators

• Hospital Vall d'Hebron: lead

Study Sites (1)

Department of HPB Surgery and Transplants, Hospital Vall d´Hebron

Barcelona, 08035, Spain

RECRUITING

Related Publications (4)

• Reinert T, Henriksen TV, Christensen E, Sharma S, Salari R, Sethi H, Knudsen M, Nordentoft I, Wu HT, Tin AS, Heilskov Rasmussen M, Vang S, Shchegrova S, Frydendahl Boll Johansen A, Srinivasan R, Assaf Z, Balcioglu M, Olson A, Dashner S, Hafez D, Navarro S, Goel S, Rabinowitz M, Billings P, Sigurjonsson S, Dyrskjot L, Swenerton R, Aleshin A, Laurberg S, Husted Madsen A, Kannerup AS, Stribolt K, Palmelund Krag S, Iversen LH, Gotschalck Sunesen K, Lin CJ, Zimmermann BG, Lindbjerg Andersen C. Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stages I to III Colorectal Cancer. JAMA Oncol. 2019 Aug 1;5(8):1124-1131. doi: 10.1001/jamaoncol.2019.0528.

  PMID: 31070691 BACKGROUND

• Elez E, Chianese C, Sanz-Garcia E, Martinelli E, Noguerido A, Mancuso FM, Caratu G, Matito J, Grasselli J, Cardone C, Esposito Abate R, Martini G, Santos C, Macarulla T, Argiles G, Capdevila J, Garcia A, Mulet N, Maiello E, Normanno N, Jones F, Tabernero J, Ciardello F, Salazar R, Vivancos A. Impact of circulating tumor DNA mutant allele fraction on prognosis in RAS-mutant metastatic colorectal cancer. Mol Oncol. 2019 Sep;13(9):1827-1835. doi: 10.1002/1878-0261.12547. Epub 2019 Jul 31.

  PMID: 31322322 BACKGROUND

• Dueland S, Grut H, Syversveen T, Hagness M, Line PD. Selection criteria related to long-term survival following liver transplantation for colorectal liver metastasis. Am J Transplant. 2020 Feb;20(2):530-537. doi: 10.1111/ajt.15682. Epub 2019 Nov 28.

  PMID: 31674105 BACKGROUND

• Bonney GK, Chew CA, Lodge P, Hubbard J, Halazun KJ, Trunecka P, Muiesan P, Mirza DF, Isaac J, Laing RW, Iyer SG, Chee CE, Yong WP, Muthiah MD, Panaro F, Sanabria J, Grothey A, Moodley K, Chau I, Chan ACY, Wang CC, Menon K, Sapisochin G, Hagness M, Dueland S, Line PD, Adam R. Liver transplantation for non-resectable colorectal liver metastases: the International Hepato-Pancreato-Biliary Association consensus guidelines. Lancet Gastroenterol Hepatol. 2021 Nov;6(11):933-946. doi: 10.1016/S2468-1253(21)00219-3. Epub 2021 Sep 8.

  PMID: 34506756 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Liver Transplantation

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

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

• Ramón Charco

  Department of HPB Surgery and Transplants, Hospital Universitario Vall d´Hebron

  PRINCIPAL INVESTIGATOR

• Elena Elez

  Department of Oncology, Hospital Universitario Vall d´Hebron

  PRINCIPAL INVESTIGATOR

• Cristina Dopazo

  Department of HPB Surgery and Transplants, Hospital Universitario Vall d´Hebron

  PRINCIPAL INVESTIGATOR

• Ernest Hidalgo

  Department of HPB Surgery and Transplants, Hospital Universitario Vall d´Hebron

  STUDY CHAIR

• Itxarone Bilbao

  Department of HPB Surgery and Transplants, Hospital Universitario Vall d´Hebron

  STUDY CHAIR

• Concepción Gómez-Gavara

  Department of HPB Surgery and Transplants, Hospital Universitario Vall d´Hebron

  STUDY CHAIR

• Mireia Caralt

  Department of HPB Surgery and Transplants, Hospital Universitario Vall d´Hebron

  STUDY CHAIR

• Javier Ros

  Department of Oncology, Hospital Universitario Vall d´Hebron

  STUDY CHAIR

• Francesc Salva

  Department of Oncology, Hospital Universitario Vall d´Hebron

  STUDY CHAIR

• Isabel Campos-Varela

  Liver Unit, Department of Internal Medicine, Hospital Universitario Vall d´Hebron

  STUDY CHAIR

• Lluis Castells

  Liver Unit, Department of Internal Medicine, Hospital Universitario Vall d´Hebron

  STUDY CHAIR

Central Study Contacts

CRISTINA DOPAZO, MD/PhD

CONTACT

+34932746113; cristina.dopazo@vallhebron.cat

CRISTINA DOPAZO

CONTACT

+34932746113; cristina.dopazo@vallhebron.cat

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant surgeon, MD/PhD

Study Record Dates

• First Submitted: May 20, 2022
• First Posted: June 1, 2022
• Study Start: January 1, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: October 2, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)