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

Liver Diseases Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04965259
• Other study ID #: AHCC10 ELEGANCE
• Status: Recruiting
• Start date: April 15, 2021
• Est. completion date: February 21, 2025

Study information

• Verified date: February 2024
• Source: National Cancer Centre, Singapore
• Contact: Pierce Chow, MD, PhD
• Phone: +65 6306 5424
• Email: pierce.chow[@]duke-nus.edu.sg
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: February 21, 2025
• Est. primary completion date: February 21, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Liver Diseases

Locations

Country	Name	City	State
Singapore	Changi General Hospital	Singapore
Singapore	National Cancer Center Singapore	Singapore
Singapore	National University Hospital	Singapore
Singapore	Sengkang General Hospital	Singapore
Singapore	Singapore General Hospital	Singapore
Singapore	SingHealth Polyclinics - Bedok	Singapore
Singapore	SingHealth Polyclinics - Bukit Merah	Singapore
Singapore	SingHealth Polyclinics - Marine Parade	Singapore
Singapore	SingHealth Polyclinics - Outram	Singapore
Singapore	SingHealth Polyclinics - Pasir Ris	Singapore
Singapore	SingHealth Polyclinics - Punggol	Singapore
Singapore	SingHealth Polyclinics - Sengkang	Singapore
Singapore	SingHealth Polyclinics - Tampines	Singapore
Singapore	Tan Tock Seng Hospital	Singapore

Sponsors (7)

Lead Sponsor	Collaborator
National Cancer Centre, Singapore	Asian Microbiome Library Pte Ltd, Duke-NUS Graduate Medical School, MiRXES Pte Ltd, Nanyang Technological University, Perspectum Asia Pte Ltd, Singapore Phenome Centre

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 48 months.
Primary	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 48 months.
Primary	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 48 months
Primary	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 48 months.