HepatoPredict Prognostic Tool for the Decision of Liver Transplant in Hepatocellular Carcinoma (HepatoPredict)

Evaluation of the HepatoPredict Prognostic Tool in the Decision of Liver Transplant in Hepatocellular Carcinoma

Liver transplant is the most effective treatment for hepatocellular carcinoma (HCC) in cirrhosis. Due to organs shortage, the proper selection of patients is imperative. Prevailing clinical morphological models used in most centres (Milan Criteria), can exclude potential candidates and include patients with aggressive biological behaviour. To more accurately select candidates for liver transplant, the inclusion of criteria that could predict the behaviour and aggressiveness of tumours, such as molecular markers, might be useful.

The investigators propose the use of a new algorithm (HepatoPredict Prognostic Tool), that combine clinical and molecular criteria that address the biology of tumours, in a single centre prospective, intervention study. Data from the "HepatoPredict genomic signature" are added to the clinical and imagiology algorithm. Based on this tool, patients outside the usual eligibility criteria for liver transplant will be proposed for this treatment. These patients will be transplanted with marginal livers or with livers from patients with Familial Amyloid Polyneuropathy, not competing with patients on the waiting list. Patients will be followed up to 60 months after transplant, to assess survival and HCC recurrence with biannual imagiology screening. Survival and disease-free-survival rates will be compared with those obtained by the usual management of patients included and excluded by Milan Criteria.

Study Overview

• Status: Recruiting
• Conditions: Recurrence Tumor; Hepatocellular Carcinoma, Scirrhous
• Intervention / Treatment: Procedure: liver transplant

Detailed Description

Liver transplant is the most effective treatment for hepatocellular carcinoma (HCC) in cirrhosis. Due to organs shortage, the proper selection of patients is imperative. Prevailing clinical morphological models used in most centres (Milan Criteria), can exclude potential candidates and include patients with aggressive biological behaviour. To more accurately select candidates for liver transplant, the inclusion of criteria that could predict the behaviour and aggressiveness of tumours, such as molecular markers, might be useful. The investigators propose the use of a new algorithm (HepatoPredict Prognostic Tool, Ophiomics), combining morphologic information, clinical and molecular criteria, in a prospective, intervention, single centre study.

Patients aged 18 to 70 years, with HCC in cirrhosis, not eligible for liver transplant under the "Milan Criteria", whom had the following morphologic characteristics: total tumour volume below 500 cm3, total number of tumour lesions below 10 and maximum individual tumour diameter below 10 cm, will be proposed for the "HepatoPredict genomic signature" analysis (Ophiomics), obtained from DNA of tumor samples. Those considered candidates by the algorithm are to be proposed for transplant with marginal livers or with livers from patients with Familial Amyloid Polyneuropathy.

Patients will be followed up to 60 months after transplant, to assess survival and HCC recurrence with biannual imagiology screening by triphasic CT scan. Additionally, circulating tumour DNA will be assessed previously to the transplant and biannually for up to 60 months. Survival and disease-free-survival rates will be compared with those obtained with the usual management of patients included and excluded by Milan Criteria, both in the same referral transplant center and in the published literature.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hugo Pinto-Marques, MD PhD; Phone Number: +351917302214; Email: hugo.marques3@chlc.min-saude.pt
• Study Contact Backup: Name: Sílvia Gomes-da-Silva, MD; Phone Number: +351916876393; Email: silvia.silva@chlc.min-saude.pt

Study Locations

• Portugal
  • Lisboa, Portugal, 1069-166
    • Recruiting
    • Centro Hepato-bilio-pancreático e de Transplantação do Hospital Curry Cabral
    • Contact: Hugo Pinto-Marques, MD PhD; Phone Number: +351917302214; Email: hugo.marques3@chlc.min-saude.pt
    • Contact: Luis Pereira-de-Silva, MD PhD; Phone Number: 51402 +351213596402; Email: centro.investigacao@chlc.min-saude.pt
    • Sub-Investigator: Sílvia Gomes-da-Silva, MD
    • Sub-Investigator: Jose Pereira-Leal, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Hepatocellular carcinoma associated with cirrhosis
• Ages between 18 and 70 years
• Total tumour volume below 500 cm3
• Total number of tumour lesions below 10
• Maximum individual tumour diameter below 10 cm

Exclusion Criteria:

• eligible under the "Milan Criteria"

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: liver transplant outside the "Milan Criteria"; patients with hepatocellular carcinoma, outside the "Milan Criteria", that complied with the proposed HepatoPredictTool, submitted to liver transplant	Procedure: liver transplant; liver transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
death	death by any cause	from 6 months after liver transplant up to 60 months
hepatocellular carcinoma recurrence	identification of hepatocellular carcinoma recurrence through biannual triphasic CT scan	from 6 months after liver transplant up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hepatocellular carcinoma recurrence through liquid biopsy	early identification of hepatocellular carcinoma DNA through biannual serum samples (liquid biopsy)	from 6 months after liver transplant up to 60 months

Collaborators and Investigators

• Sponsor: Centro Hospitalar de Lisboa Central
• Collaborators: Ophiomics - Precision Medicine
• Investigators: Principal Investigator: Hugo Pinto-Marques, MD PhD, Centro Hospitalar Universitário de Lisboa Central

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2021
• Primary Completion (Anticipated): October 30, 2028
• Study Completion (Anticipated): December 31, 2029

Study Registration Dates

• First Submitted: July 31, 2020
• First Submitted That Met QC Criteria: July 31, 2020
• First Posted (Actual): August 5, 2020

Study Record Updates

• Last Update Posted (Actual): June 6, 2022
• Last Update Submitted That Met QC Criteria: June 3, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; biomarkers; prognosis; cirrhosis; liver transplant; tumor recurrence
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Recurrence; Adenocarcinoma, Scirrhous
• Other Study ID Numbers: CHULC.CI.HCC.2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No