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

NCT04965259 | Active Not Recruiting DMC

• 1 other identifier: AHCC10 ELEGANCE
• Study Type: observational
• Target: 2,002
• Locations: 1 country
• Sites: 14

Brief Summary

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.

Conditions

Liver Diseases

Keywords

Hepatocellular Carcinoma(HCC); Surveillance; Patients-at-risk; miRNA; Precision medicine; Gut microbiota; Metabolites; Microbiome biomarkers; Circulating biomarkers; MRI

Outcome Measures

Primary Outcomes (4)

• Changes in the profile of circulating micro-RNA biomarkers as high-risk patients develop HCC

  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 70 months.

• value of cT1, PDFF and T2* levels to predict individual's risk of developing and progression of HCC.

  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 70 months.

• Changes in the profile of gut microbiota as high-risk patients develop HCC.

  Changes in the profile of gut microbiota as high-risk patients develop HCC.

  Baseline and every 6 months thereafter, up to 70 months

• Changes in the profile of metabolome in urine and plasma as high-risk patients develop HCC.

  Changes in the profile of metabolome in urine and plasma as high-risk patients develop HCC.

  Baseline and every 6 months thereafter, up to 70 months.

Eligibility Criteria

• Age: 40 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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:
• liver cirrhosis of any etiology, identified by elastography (liver stiffness \> 13 kPa), US, CT, MRI or liver biopsy, Child-Pugh class A and B
• non-cirrhotic chronic viral hepatitis (B or C) or both
• non-alcoholic fatty liver disease (NAFLD)
• non-alcoholic steatohepatitis (NASH)
• 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

You may not qualify if:

• Patient with confirmed diagnosis of HCC by the American Association for the Study of the Liver Disease (AASLD) 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

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead
• Duke-NUS Graduate Medical School: collaborator
• Singapore Phenome Centre: collaborator
• Nanyang Technological University: collaborator
• MiRXES Pte Ltd: collaborator
• Perspectum Asia Pte Ltd: collaborator
• Asian Microbiome Library Pte Ltd: collaborator

Study Sites (14)

National University Hospital

Singapore, 119228, Singapore

Location

SingHealth Polyclinics - Bukit Merah

Singapore, 150163, Singapore

Location

National Cancer Center Singapore

Singapore, 168583, Singapore

Location

SingHealth Polyclinics - Outram

Singapore, 168937, Singapore

Location

Singapore General Hospital

Singapore, 169608, Singapore

Location

Tan Tock Seng Hospital

Singapore, 308433, Singapore

Location

SingHealth Polyclinics - Marine Parade

Singapore, 440080, Singapore

Location

SingHealth Polyclinics - Bedok

Singapore, 469662, Singapore

Location

SingHealth Polyclinics - Pasir Ris

Singapore, 519457, Singapore

Location

SingHealth Polyclinics - Tampines

Singapore, 529203, Singapore

Location

Changi General Hospital

Singapore, 529889, Singapore

Location

Sengkang General Hospital

Singapore, 544886, Singapore

Location

SingHealth Polyclinics - Sengkang

Singapore, 545025, Singapore

Location

SingHealth Polyclinics - Punggol

Singapore, 820681, Singapore

Location

Biospecimen

Retention: SAMPLES WITH DNA

Bloods shall be used for relevant laboratory assessments. Blood, urine and stool samples shall be used for miRNA, microbiome and metabolome profiling.

MeSH Terms

Conditions

Liver Diseases; Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site

Study Officials

• Pierce Chow, MD, PhD

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 7, 2021
• First Posted: July 16, 2021
• Study Start: April 15, 2021
• Primary Completion: March 11, 2025
• Study Completion (Estimated): December 21, 2026
• Last Updated: July 2, 2025

Record last verified: 2025-06

Locations

SG (14)