Early Detection of Hepatocellular Carcinoma in a High-risk Prospective Cohort (ELEGANCE)

February 28, 2024 updated by: National Cancer Centre, Singapore

Early Detection of Hepatocellular Carcinoma (HCC): miRNA, Microbiome and Imaging Biomarkers in the Evolution of Chronic Liver Disease in a High-risk Prospective Cohort (ELEGANCE)

Hepatocellular carcinoma (HCC) is the 7th most common cause of cancer death globally but only 20% are diagnosed in its early stages where cure is possible. Current standard-of-care surveillance of patients at high risk of developing HCC with 6-monthly serum alpha-fetoprotein (AFP) and ultrasound imaging (US) has a sensitivity of approximately 63% for detecting early HCC. There is an urgent need for a more efficacious and convenient modality of surveillance of high-risk patients to diagnose HCC at an early stage.

This prospective study aims to address this unmet clinical need by validating a panel of circulating miRNA biomarkers to develop an in-vitro diagnostic (IVD) kit for the detection of early HCC in a cohort of high-risk patients.

Additionally, this study also aims to develop a multi-parametric MRI-based AI algorithm to quantify individual risks of developing HCC and to predict the progression of chronic liver disease in this cohort to enable targeted surveillance. Lastly, by identifying changes in the microbiome and metabolites as HCC develops in this cohort enables the establishment of actionable biomarkers that can prevent and predict the development of HCC.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Eligible patients will receive 6-monthly standard-of-care surveillance (US, serum AFP and liver function test) for HCC until end of study or up to a maximum of 7 assessments (1 baseline and 6 follow-up assessments). There will be an option for patients to continue to receive standard-of-care surveillance for HCC until end of study or up to 2 additional assessments (Visits 8-9), whichever occurs first.

Patients with elevated AFP or abnormalities detected on US will be investigated with multi-phasic CT scan or MRI to confirm or refute the diagnosis of HCC. Additionally, patients shall be scheduled for sequential bio-samples collection (blood, urine and stool) and blood tests (Hba1c and Lipid Panel) during the course of the study.

Study Type

Observational

Enrollment (Estimated)

2000

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

  • Singapore
      • Singapore, Singapore, 169608
        • Recruiting
        • Singapore General Hospital
        • Contact:
          • Jason Pik Eu CHANG, MD
      • Singapore, Singapore, 308433
        • Recruiting
        • Tan Tock Seng Hospital
        • Contact:
          • Wei Lyn YANG, MD
      • Singapore, Singapore, 119228
        • Recruiting
        • National University Hospital
        • Contact:
          • Guan Huei LEE, MD, PhD
      • Singapore, Singapore, 529889
        • Recruiting
        • Changi General Hospital
        • Contact:
          • Eugene Yu Jun WONG, MD
      • Singapore, Singapore, 519457
        • Recruiting
        • SingHealth Polyclinics - Pasir Ris
        • Contact:
          • Ngiap Chuan TAN, MD
      • Singapore, Singapore, 544886
        • Recruiting
        • Sengkang General Hospital
        • Contact:
          • Marianne Anastasia DE ROZA, MD
      • Singapore, Singapore, 150163
        • Recruiting
        • SingHealth Polyclinics - Bukit Merah
        • Contact:
          • Sabrina WEE, MD
      • Singapore, Singapore, 168937
        • Recruiting
        • SingHealth Polyclinics - Outram
        • Contact:
          • Kok Kiong ONG, MD
      • Singapore, Singapore, 440080
        • Recruiting
        • SingHealth Polyclinics - Marine Parade
        • Contact:
          • Kee Tung TAN, MD
      • Singapore, Singapore, 469662
        • Recruiting
        • SingHealth Polyclinics - Bedok
        • Contact:
          • Oi Fong CHONG, MD
      • Singapore, Singapore, 529203
        • Recruiting
        • SingHealth Polyclinics - Tampines
        • Contact:
          • SULAIHA Binte Ithnin, MD
      • Singapore, Singapore, 545025
        • Recruiting
        • SingHealth Polyclinics - Sengkang
        • Contact:
          • Jeremy Wei Song CHOO, MD
      • Singapore, Singapore, 820681
        • Recruiting
        • SingHealth Polyclinics - Punggol
        • Contact:
          • Xin Yi YEAP, MD
      • Singapore, Singapore, 168583
        • Recruiting
        • National Cancer Center Singapore
        • Contact:
          • Pierce CHOW, MD, PhD
        • Contact:
          • Han Chong TOH, MD

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

40 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients at high-risk of developing HCC forming a cohort of 750 patients with cirrhosis from any etiology, 930 chronic hepatitis B without significant cirrhosis, 20 chronic hepatitis C without significant cirrhosis and 300 NAFLD/NASH without significant cirrhosis.

Description

Inclusion Criteria:

  • Male and female patients, 50 to 90 years of age at the time of signing the informed consent form, except for patients recruited under the cirrhotic group, patients of 40 to 90 years of age can be included.
  • Patient has serum alpha-fetoprotein (AFP) within normal range of the investigating laboratory in the past 3 months. For patients with AFP level out of the normal range of the investigating laboratory and up to 15.0ug/L, patient will be eligible if patient has a CT/MRI scan that exclude HCC in the past 3 months.
  • Patient has ultrasound hepatobiliary system (US HBS) that does not show lesion suspicious for HCC or, CT / MRI scan that exclude HCC, in the past 3 months
  • Patient is estimated to survive more than 3 years

  • Patient with any of the following chronic liver disease:

    1. liver cirrhosis of any etiology, identified by elastography (liver stiffness > 13 kPa), US, CT, MRI or liver biopsy, Child-Pugh class A and B
    2. non-cirrhotic chronic viral hepatitis (B or C) or both
    3. non-alcoholic fatty liver disease (NAFLD) with liver stiffness > 9 kPa
    4. non-alcoholic steatohepatitis (NASH) with liver stiffness > 9 kPa
  • Patient is able to comply with scheduled visits, assessments and other study procedures
  • Patient is willing to provide informed consent before enrolment in the study

Exclusion Criteria:

  • Patient with confirmed diagnosis of HCC by the American Association for the Study of the Liver Disease (AASLDC) imaging criteria or histology / cytology within the last 5 years
  • Patient with Child-Pugh C cirrhosis at time of enrolment (based on the judgement of the Investigator)
  • Patient with active hepatic encephalopathy at time of enrolment
  • Patient is known to be positive for the Human Immunodeficiency Virus (HIV)
  • Patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the study procedures
  • Patient is unable to provide informed consent or refuse blood taking
  • Patient has any other condition which, in the opinion of the Investigators, would make the patient unsuitable for enrolment or could interfere with completion of the study

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in the profile of circulating micro-RNA biomarkers as high-risk patients develop HCC
Time Frame: Baseline and every 6 months thereafter, and at HCC diagnosis every 6 months thereafter up to 48 months.
Changes in the profile of circulating micro-RNA biomarkers as high-risk patients develop HCC
Baseline and every 6 months thereafter, and at HCC diagnosis every 6 months thereafter up to 48 months.
value of cT1, PDFF and T2* levels to predict individual's risk of developing and progression of HCC.
Time Frame: Baseline and upon elevated AFP or US which is suggestive of HCC, up to 48 months.
value of cT1, PDFF and T2* levels to predict individual's risk of developing and progression of HCC.
Baseline and upon elevated AFP or US which is suggestive of HCC, up to 48 months.
Changes in the profile of gut microbiota as high-risk patients develop HCC.
Time Frame: Baseline and every 6 months thereafter, up to 48 months
Changes in the profile of gut microbiota as high-risk patients develop HCC.
Baseline and every 6 months thereafter, up to 48 months
Changes in the profile of metabolome in urine and plasma as high-risk patients develop HCC.
Time Frame: Baseline and every 6 months thereafter, up to 48 months.
Changes in the profile of metabolome in urine and plasma as high-risk patients develop HCC.
Baseline and every 6 months thereafter, up to 48 months.

Collaborators and Investigators

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

Sponsor

National Cancer Centre, Singapore

Collaborators

Nanyang Technological University
Duke-NUS Graduate Medical School
MiRXES Pte Ltd
Singapore Phenome Centre
Perspectum Asia Pte Ltd
Asian Microbiome Library Pte Ltd

Investigators

  • Principal Investigator: Pierce CHOW, MD, PhD, National Cancer Centre, Singapore

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)

April 15, 2021

Primary Completion (Estimated)

February 21, 2025

Study Completion (Estimated)

February 21, 2025

Study Registration Dates

First Submitted

July 7, 2021

First Submitted That Met QC Criteria

July 7, 2021

First Posted (Actual)

July 16, 2021

Study Record Updates

Last Update Posted (Estimated)

February 29, 2024

Last Update Submitted That Met QC Criteria

February 28, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AHCC10 ELEGANCE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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