Prospective Cohort for Early Detection of Liver Cancer (Pearl)

September 12, 2022 updated by: University of Oxford
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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Anticipated)

3000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United Kingdom
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX3 9DU
        • Recruiting
        • Hepatology Clinical Trial Unit, John Radcliffe Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients with Child-Pugh (CP) A or B cirrhosis with no current or historical diagnosis of HCC. Diagnosis of cirrhosis can be based on, laboratory, imaging or histology criteria (e.g. the latter including Ishak stage >=5). Participants can be recruited to other interventional studies for treatment of cirrhosis or prevention of HCC prior to or during participation in the Pearl study.

Description

Inclusion Criteria:

  1. Patients of all genders, age >18 years
  2. Participant is willing and able to give informed consent for participation in the study.
  3. 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

  1. Histological assessment (Ishak stage 5 or 6) or
  2. 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:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Pearl Cohort
All 3000 patients recruited to the Pearl study
Other: Blood and Urine samples
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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:

  1. detection of epigenetic (e.g. methylation profiling) and genetic mutations, and copy number variations in circulating tumour DNA;
  2. multiparametric MRI liver imaging including MR biomarkers of inflammation, fibrosis, fat and iron content;
  3. host genetic makeup (relevant variants identified through Genome Wide Association Studies);
  4. detection of autoantibodies to tumour associated antigens;
  5. epitope mapping of circulating antibody repertoire using random peptide libraries;
  6. protein biomarkers including the L3 isoform of alphafetoprotein, and des-gammacarboxy- prothrombin;
  7. proteomic and metabolomic profiling, including steroid metabolic signatures in urine.
When 50 cases of HCC have accumulated through to study completion; up to 5 years
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:

  1. detection of epigenetic (e.g. methylation profiling) and genetic mutations, and copy number variations in circulating tumour DNA;
  2. multiparametric MRI liver imaging including MR biomarkers of inflammation, fibrosis, fat and iron content;
  3. host genetic makeup (relevant variants identified through Genome Wide Association Studies);
  4. detection of autoantibodies to tumour associated antigens;
  5. epitope mapping of circulating antibody repertoire using random peptide libraries;
  6. protein biomarkers including the L3 isoform of alphafetoprotein, and des-gammacarboxy- prothrombin;
  7. proteomic and metabolomic profiling, including steroid metabolic signatures in urine.
When 50 cases of HCC have accumulated through to study completion; up to 5 years
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:

  1. detection of epigenetic (e.g. methylation profiling) and genetic mutations, and copy number variations in circulating tumour DNA;
  2. multiparametric MRI liver imaging including MR biomarkers of inflammation, fibrosis, fat and iron content;
  3. host genetic makeup (relevant variants identified through Genome Wide Association Studies);
  4. detection of autoantibodies to tumour associated antigens;
  5. epitope mapping of circulating antibody repertoire using random peptide libraries;
  6. protein biomarkers including the L3 isoform of alphafetoprotein, and des-gammacarboxy- prothrombin;
  7. proteomic and metabolomic profiling, including steroid metabolic signatures in urine.
When 50 cases of HCC have accumulated through to study completion; up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Throughout study to completion; 5 years
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
At 1, 3 and 5 year post- baseline.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Collaborators

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

Investigators

  • Principal Investigator: Ellie Barnes, University of Oxford

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 23, 2022

Primary Completion (Anticipated)

July 1, 2037

Study Completion (Anticipated)

July 1, 2037

Study Registration Dates

First Submitted

August 1, 2022

First Submitted That Met QC Criteria

September 12, 2022

First Posted (Actual)

September 15, 2022

Study Record Updates

Last Update Posted (Actual)

September 15, 2022

Last Update Submitted That Met QC Criteria

September 12, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PEARL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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