Neoplasms

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Carcinoma, Hepatocellular

Liver Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

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Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Chronic Graft Versus Host Disease

Hematinics

All Drugs and Chemicals

Liver Extracts

Pierce Chow, MD, PhD

Guan Huei LEE, MD, PhD

Sabrina WEE, MD

Pierce CHOW, MD, PhD

Han Chong TOH, MD

Kok Kiong ONG, MD

Jason Pik Eu CHANG, MD

Wei Lyn YANG, MD

Kee Tung TAN, MD

Oi Fong CHONG, MD

Ngiap Chuan TAN, MD

SULAIHA Binte Ithnin, MD

Eugene Yu Jun WONG, MD

Marianne Anastasia DE ROZA, MD

Jeremy Wei Song CHOO, MD

Xin Yi YEAP, MD

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.

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.

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

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

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)

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

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

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

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

Duke-NUS Graduate Medical School

Singapore Phenome Centre

Nanyang Technological University

MiRXES Pte Ltd

Perspectum Asia Pte Ltd

Asian Microbiome Library Pte Ltd

National Cancer Centre, Singapore

Symptoms and General Pathology

Recurrence

Glenn Kunnath BONNEY, MD

Brian GOH, MD

Vishalkumar Girishchandra SHELAT, MD

Adrian CHIOW, MD

Juinn Huar KAM, MD

Hepatocellular carcinoma (HCC) is the 4th most common cause of cancer death globally but only 20% are diagnosed in its early stages where curative treatment can be carried out. 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. In another study (AHCC10 ELEGANCE, NCT04965259), 2,000 patients at risk of developing HCC will be enrolled to develop the 1st miRNA in-vitro diagnostic (IVD) kit for HCC that has higher accuracy and better ease of use compared with the extant combination of AFP and US.

This prospective study will act as a positive control to the AHCC10 ELEGANCE Study and aims to address the absence of efficacious modalities of surveillance by validating a panel of circulating miRNA biomarkers signatures with histologically proven HCC. This study will determine progressive changes in the profiles of miRNA signatures pre- and post- surgical resection to identify signatures predictive of recurrence.

Additionally, this study also aims to identify changes in key metabolites and microbiome with correlation to changes in choline, bile acid and tryptophan metabolic pathways with changes in the composition and function of gut microbiota to establish actionable biomarkers that can predict HCC recurrence.

This is a prospective study involving 100 patients with diagnosis of hepatocellular carcinoma (HCC) confirmed by histology at surgical resection. Eligible patients will receive CT scans at 6 months and 12 months post-surgery to monitor for recurrence. Pre- and post-surgery bio-samples (blood, urine, stool) will also be collected to monitor changes in profiles of miRNA, metabolome and microbiome.

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

Prospective Cohort Study of Changes in Circulatory MicroRNA of Resected Hepatocellular Carcinoma

Prospective Cohort Study of Changes in Circulatory MicroRNA After Surgical Resection of Hepatocellular Carcinoma (HCC) (PROSECT)

Changes in the profile of circulating micro-RNA biomarkers pre- and post- surgical resection.

Differences in the profile of gut microbiota among HCC and healthy population retrieved from database.

Changes in the profile of metabolome in urine and plasma pre- and post- surgical resection.

Asian Microbiome Library (AMiLi) Pte Ltd

Study title	NCT ID	Conditions	Eligibility	Organization
Early Detection of Hepatocellular Carcinoma in a High-risk Prospective Cohort (ELEGANCE)	NCT04965259	Liver Diseases	40 Years - 90 Years	National Cancer Centre, Singapore
Prospective Cohort Study of Changes in Circulatory MicroRNA of Resected Hepatocellular Carcinoma	NCT05148572	Hepatocellular ...	21 Years - 90 Years	National Cancer Centre, Singapore
Early Detection of Hepatocellular Carcinoma in a High-risk Prospective Cohort (ELEGANCE)	NCT04965259	Liver Diseases	40 Years - 90 Years	National Cancer Centre, Singapore

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