Skip to main content
OpenTrials
Recruiting

NCT Number: NCT05541601

Prospective Cohort for Early Detection of Liver Cancer

This study aims to recruit 3000 people with liver cirrhosis into a Prospective cohort for early detection of Liver cancer - the Pearl cohort. The study team believe that using a combination of novel tests may improve the detection of early Hepatocellular Carcinoma (HCC).

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Cirrhosis Adenocarcinoma Carcinoma Carcinoma, Hepatocellular Digestive System Diseases Digestive System Neoplasms Fibrosis Hepatocellular Carcinoma Liver Diseases Liver Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year–100 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Hepatology Clinical Trial Unit, John Radcliffe Hospital

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location status: Recruiting

Location contact

Eleanor Barnes, Prof

CONTACT

[email protected]

About this study

During a four-year follow-up period, around 100 Pearl patients are expected to be diagnosed with HCC. Blood, urine, clinical and imaging data will be collected over the follow up period. The samples will be used to identify a range of tests (including genetic, protein and other biomarkers), which along with the clinical data will hopefully identify those most at risk of developing HCC, and to identify HCC at the earliest possible time points.

Who can participate

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients of all genders, age >18 years
  • Participant is willing and able to give informed consent for participation in the study.
  • Evidence of cirrhosis CP A or B (as defined below, cirrhosis ever diagnosed), with an underlying aetiology of at least one of the following: chronic Hepatitis B Virus (HBV) infection, chronic Hepatitis C Virus (HCV) infection, alcoholic liver disease, non-alcoholic fatty liver disease or haemochromatosis

Cirrhosis Diagnosis Definition

  • Histological assessment (Ishak stage 5 or 6) or
  • At least one of the following:

i. Validated non-invasive marker of fibrosis including fibroscan, AST to Platelet Ratio Index (APRI) score >2 or Enhanced Liver Fibrosis (ELF) score >10.48 or Fibrotest score >0.73. Fibroscan readings should be assessed by aetiology as below:

  • HBV: >=10 kPa
  • HCV: >=14.5 kPa
  • Alcoholic Liver Disease (ALD): >=19.5 kPa
  • Non-alcoholic fatty liver disease (NAFLD): >=15 kPa
  • Haemochromatosis: >=12kPa ii. Evidence of varices at endoscopy or imaging in the context of a patent portal vein iii. Definitive radiological evidence of cirrhosis (i.e. nodularity of liver and splenomegaly on Ultrasound/CT)

Exclusion criteria

  • Diagnosis of current OR historical hepatocellular carcinoma
  • Liver transplant recipients or patients on active listing for liver transplantation
  • Child-Pugh C cirrhosis
  • In the view of the clinician, if the patient has a co-morbidity likely to lead to death within the following 12 months
  • In the view of the clinician, if the patient was not thought to be suitable for HCC surveillance

Treatment and study plan

Blood and Urine samples

Other

The samples will be used to identify a range of tests (including genetic, protein and other biomarkers), which along with the clinical data will hopefully identify those most at risk of developing HCC, and to identify HCC at the earliest possible time points.

Primary outcomes

  1. Sensitivity of novel diagnostic approaches for the early diagnosis of HCC in enrolled patients who are diagnosed with HCC by conventional approaches.

    Time frame: When 50 cases of HCC have accumulated through to study completion; up to 5 years

    Diagnostic approaches to be tested will include:

    • detection of epigenetic (e.g. methylation profiling) and genetic mutations, and copy number variations in circulating tumour DNA;
    • multiparametric MRI liver imaging including MR biomarkers of inflammation, fibrosis, fat and iron content;
    • host genetic makeup (relevant variants identified through Genome Wide Association Studies);
    • detection of autoantibodies to tumour associated antigens;
    • epitope mapping of circulating antibody repertoire using random peptide libraries;
    • protein biomarkers including the L3 isoform of alphafetoprotein, and des-gammacarboxy- prothrombin;
    • proteomic and metabolomic profiling, including steroid metabolic signatures in urine.

  2. Specificity of novel diagnostic approaches for the early diagnosis of HCC in enrolled patients who are diagnosed with HCC by conventional approaches.

    Time frame: When 50 cases of HCC have accumulated through to study completion; up to 5 years

    Diagnostic approaches to be tested will include:

    • detection of epigenetic (e.g. methylation profiling) and genetic mutations, and copy number variations in circulating tumour DNA;
    • multiparametric MRI liver imaging including MR biomarkers of inflammation, fibrosis, fat and iron content;
    • host genetic makeup (relevant variants identified through Genome Wide Association Studies);
    • detection of autoantibodies to tumour associated antigens;
    • epitope mapping of circulating antibody repertoire using random peptide libraries;
    • protein biomarkers including the L3 isoform of alphafetoprotein, and des-gammacarboxy- prothrombin;
    • proteomic and metabolomic profiling, including steroid metabolic signatures in urine.

  3. Positive/Negative predictive values of novel diagnostic approaches for the early diagnosis of HCC in enrolled patients who are diagnosed with HCC by conventional approaches.

    Time frame: When 50 cases of HCC have accumulated through to study completion; up to 5 years

    Diagnostic approaches to be tested will include:

    • detection of epigenetic (e.g. methylation profiling) and genetic mutations, and copy number variations in circulating tumour DNA;
    • multiparametric MRI liver imaging including MR biomarkers of inflammation, fibrosis, fat and iron content;
    • host genetic makeup (relevant variants identified through Genome Wide Association Studies);
    • detection of autoantibodies to tumour associated antigens;
    • epitope mapping of circulating antibody repertoire using random peptide libraries;
    • protein biomarkers including the L3 isoform of alphafetoprotein, and des-gammacarboxy- prothrombin;
    • proteomic and metabolomic profiling, including steroid metabolic signatures in urine.

Secondary outcomes

  1. To develop models that can be used to "risk-stratify" cirrhosis patients according to their future risk of HCC

    Time frame: Throughout study to completion; 5 years

    The Harrell's Concordance Index (C-index) will be calculated for each biomarker/model of interest. The minimum and maximum C-index scores are 0 and 1, respectively, where the higher the score the better the biomarker/model is at identifying HCC risk. C-index values indicate the degree to which individuals who develop HCC have a higher risk score than those who do not. C-index values will be adapted to incorporate non-HCC mortality as a competing risk. The C-index value will be used to identify the biomarkers/models with the best discriminative ability.

  2. To better understand the incidence of HCC in a UK population stratified by underlying cirrhosis aetiology

    Time frame: At 1, 3 and 5 year post- baseline.

    Cumulative incidence of HCC according to cirrhosis aetiology

Study contacts

Contact information is provided by the study sponsor or research team.

Study Coordinator

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

University of Oxford

Other

Collaborators

  • Cancer Research UK
  • Glasgow Caledonian University
  • OncImmune Ltd
  • Perspectum
  • Roche Diagnostic Ltd.
  • University of Nottingham

Registry information

Acronym: Pearl

Important dates

Study start
2022
Primary completion
2037
Study completion
2037
First posted
Sep 15, 2022
Registry last updated
Sep 15, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.