Clinical trial NCT04965259: Early Detection of Hepatocellular Carcinoma in a High-risk Prospective Cohort (ELEGANCE)
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)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Liver Diseases
Keywords: Hepatocellular Carcinoma(HCC)
Surveillance
Patients-at-risk
miRNA
Precision medicine
Gut microbiota
Metabolites
Microbiome biomarkers
Circulating biomarkers
MRI
Lead sponsor: National Cancer Centre, Singapore
Sponsor class: OTHER
Collaborators: name: Duke-NUS Graduate Medical School
name: Singapore Phenome Centre
name: Nanyang Technological University
name: MiRXES Pte Ltd
name: Perspectum Asia Pte Ltd
name: Asian Microbiome Library Pte Ltd
First posted: 2021-07-16
Enrollment: 2003
Sex: ALL
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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 6 additional assessments (Visits 8-13), 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.

Eligibility criteria: 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)
  4. 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Changes in the profile of circulating micro-RNA biomarkers as high-risk patients develop HCC
timeFrame: Baseline and every 6 months thereafter, and at HCC diagnosis every 6 months thereafter up to 70 months.
measure: value of cT1, PDFF and T2* levels to predict individual's risk of developing and progression of HCC.
timeFrame: Baseline and upon elevated AFP or US which is suggestive of HCC, up to 70 months.
measure: Changes in the profile of gut microbiota as high-risk patients develop HCC.
timeFrame: Baseline and every 6 months thereafter, up to 70 months
measure: Changes in the profile of metabolome in urine and plasma as high-risk patients develop HCC.
timeFrame: Baseline and every 6 months thereafter, up to 70 months.
Secondary outcomes:
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: SingHealth Polyclinics - Bukit Merah
city: Singapore
country: Singapore
facility: National Cancer Center Singapore
city: Singapore
country: Singapore
facility: SingHealth Polyclinics - Outram
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: Singapore
country: Singapore
facility: SingHealth Polyclinics - Marine Parade
city: Singapore
country: Singapore
facility: SingHealth Polyclinics - Bedok
city: Singapore
country: Singapore
facility: SingHealth Polyclinics - Pasir Ris
city: Singapore
country: Singapore
facility: SingHealth Polyclinics - Tampines
city: Singapore
country: Singapore
facility: Changi General Hospital
city: Singapore
country: Singapore
facility: Sengkang General Hospital
city: Singapore
country: Singapore
facility: SingHealth Polyclinics - Sengkang
city: Singapore
country: Singapore
facility: SingHealth Polyclinics - Punggol
Study officials:
affiliation: National Cancer Centre, Singapore
name: Pierce Chow, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: