NCT05541601

Brief Summary

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).

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
3,000

participants targeted

Target at P75+ for all trials

Timeline
136mo left

Started Feb 2022

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress27%
Feb 2022Jul 2037

Study Start

First participant enrolled

February 23, 2022

Completed
5 months until next milestone

First Submitted

Initial submission to the registry

August 1, 2022

Completed
2 months until next milestone

First Posted

Study publicly available on registry

September 15, 2022

Completed
14.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2037

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2037

Last Updated

September 15, 2022

Status Verified

September 1, 2022

Enrollment Period

15.4 years

First QC Date

August 1, 2022

Last Update Submit

September 12, 2022

Conditions

CirrhosisHepatocellular Carcinoma

Outcome Measures

Primary Outcomes (3)

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

    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.

    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.

    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 Outcomes (2)

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

    Throughout study to completion; 5 years

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

    At 1, 3 and 5 year post- baseline.

Study Arms (1)

Pearl Cohort

All 3000 patients recruited to the Pearl study

Other: Blood and Urine samples

Interventions

Blood and Urine samplesOTHER

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.

Pearl Cohort

Eligibility Criteria

Age18 Years - 100 Years
Sexall
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability 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.

You may qualify if:

  • 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)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hepatology Clinical Trial Unit, John Radcliffe Hospital

Oxford, Oxfordshire, OX3 9DU, United Kingdom

RECRUITING

Related Publications (1)

  • Khanna K, Barnes E, Benselin J, Culver E, Irving W, Innes H, Pavlides M, Consortium D. Prospective cohort for early detection of liver cancer (Pearl): a study protocol. BMJ Open. 2024 Oct 1;14(10):e085541. doi: 10.1136/bmjopen-2024-085541.

    PMID: 39353693DERIVED

Related Links

MeSH Terms

Conditions

FibrosisCarcinoma, Hepatocellular

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and SymptomsAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Intervention Hierarchy (Ancestors)

Specimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisPuncturesSurgical Procedures, OperativeInvestigative Techniques

Study Officials

  • Ellie Barnes

    University of Oxford

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Coordinator

CONTACT

deliver-pearl@ndm.ox.ac.uk

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 1, 2022

First Posted

September 15, 2022

Study Start

February 23, 2022

Primary Completion (Estimated)

July 1, 2037

Study Completion (Estimated)

July 1, 2037

Last Updated

September 15, 2022

Record last verified: 2022-09

Locations

GB(1)