Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

All Drugs and Chemicals

Chlorotrianisene

Stereotactic ablative radiotherapy (SABR)

Re-transcatheter arterial chemoembolization (re-TACE)

Patients with HCC after incomplete TACE are randomized to stereotactic ablative radiotherapy (SABR). SABR will be delivered in 5 fractions.The preferred inter-fraction time interval is 48 hours. The entire treatment with 10 days is preferred.

Patients with HCC after incomplete TACE are randomized to further re-TACE.

Re-Transcatheter arterial chemoembolization (re-TACE)

Shih-Kai Hung, PhD

Liang-Cheng Chen, MD

Till now, trans-arterial chemoembolization (TACE) is still one of the common modalities in treating hepatocellular carcinoma patients with unresectable intermediate stage. However, residual viable HCC after TACE is not uncommon, leading to a poor overall survival after TACE alone. Recently, stereotactic ablative radiotherapy (SABR) has been reported to be potentially useful for curatively managing early-stage HCC in retrospective studies. Thus, conducting a randomized clinical trial to test the role of SABR in eradicating post-TACE residual tumors is therefore encouraged. The present phase-III trial intended to compare clinical outcomes between TACE + SABR and TACE + re-TACE for HCC patients with post-prior-TACE residual tumors.

Developing effective treatment modalities is crucial in managing HCC patients with unresectable intermediate stage. Nowadays, many therapies have been used for treating this group of HCC patients, including TACE. However, residual tumors after TACE are not uncommon. In conventional, re-TACE is recommended for managing residual tumors. However, accumulated overall survival is still poor in consecutive TACEs, leading to a low rate of \<20% in 5 years.

In this regard, radiotherapy has been proved to be effective in managing HCC patients, especially a novel technique named SABR. When compared with conventional-fractionated radiotherapy, SABR demonstrated better treatment responses with fewer side effects in managing primary or metastatic liver tumors. In the literature, phase I and II trials of TACE plus SABR showed excellent local control rates and promising 1- and 2-year survival rates. However, till now, there is no head-to-head comparison between TACE + SABR and consecutive TACEs.

Comparing Re-TACE Versus SABR for Post-prior-TACE Incompletely Regressed HCC: a Randomized Controlled Trial (TASABR)

Comparing Re-trans-catheter Arterial Chemoembolization Versus Stereotactic Ablative Radiotherapy for Hepatocellular Carcinoma Patients Who Had Incomplete Response After Prior TACE (TASABR Trial): a Randomized Controlled Trial

The freedom from local progression is defined as no in-field progressive disease. It will be estimated by Kaplan-Meier and Cox regression model adjusting for the competing risks

To estimate the rates of overall survival. It will be estimated by Kaplan-Meier and Cox regression model adjusting for the competing risks

To estimate the rates of progression-free survival. It will be estimated by Kaplan-Meier and Cox regression model adjusting for the competing risks

To estimate the response rate. It will be estimated by Kaplan-Meier and Cox regression model adjusting for the competing risks

The duration of the response is from the time response is achieved until disease progression is detected. It will be estimated by Kaplan-Meier and Cox regression model adjusting for the competing risks

To estimate the rate of acute and late treatment-related toxicity related to specific symptoms

Buddhist Tzu Chi General Hospital

Hualien Tzu Chi General Hospital

Dalin Tzu Chi General Hospital

Rare Diseases

Chronic Graft Versus Host Disease

Hematinics

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

Immunomodulating Agents

Immunologic Factors

Enrolled patients will receive CAR-T cell immunotherapy with a novel specific Chimeric antigen receptor aiming at GPC3 antigen by infusion.

This CAR-T cell immunotherapy with a novel specific Chimeric antigen receptor aiming at GPC3 antigen.

CAR-T cell immunotherapy

Lizhi Niu, PhD

The purpose of this study is to preliminarily evaluate the safety and efficacy of CAR-T cell immunotherapy for GPC3 positive hepatocellular carcinoma.

Chimeric antigen receptor (CAR) is a recombinant receptor with both antigen-binding and T cell activating functions. Chimeric antigen receptor T cell Immunotherapy has more advantages compared with conventional immunotherapy, especially in dealing with patients of hematologic malignancies and solid malignant tumors.This study design a novel specific Chimeric antigen receptor targeting glypican-3(GPC3) antigen.After CAR-T cell infusion,At periodic intervals, the investigators will evaluate clinical symptoms Improved conditions of this disease.Through this study,the investigators will evaluate the safety and efficacy of CAR-T cell immunotherapy in treating with GPC3 positive malignant glioma patients.

CAR-T Cell Immunotherapy for HCC Targeting GPC3

Chimeric Antigen Receptor-Modified T Cell (CAR-T) Immunotherapy for Hepatocellular Carcinoma (HCC) Targeting Glypican-3 (GPC3)

Radiological assessment of the therapeutic effect by systemic or local computed Tomography(CT) or positron emission tomography scan.

After CAR-T cell infusion,we will observe the potential adverse events related to the T-cell infusion such as high fever,jaundice, kidney failure and so on.

tested regularly to reflect the role of the Chimeric Antigen Receptor-Modified T Cell in the removal of residual tumor cells.

The level of CAR-T cells will be tested regularly by Real-time Quantitative Polymerase Chain Reaction Detecting System(qPCR) or Flow cytometry to evaluate the proliferation in vivo and long-term survival.

Fuda Cancer Hospital, Guangzhou

patients HCC who are going to receive surgical resection

Ming-Chih Ho, MD

Ming-Chih Ho, MD/PhD

Histological grade of hepatocellular carcinoma (HCC) is an important prognostic factor affecting patient survival. It has been divided into four grades from I to IV on the basis of histological differentiation. Grade I is the best differentiated consisting of small tumor cells arranged in thin trabeculae. Cells with higher grade are larger and less differentiated with hyperchromatic nuclei and loss of trabecular pattern.

Ultrasound is an imaging modality frequently used to evaluate liver tumors because of its convenience, real-time, less expensive and no radiation exposure. However, ultrasonographic evaluation by conventional B-mode image is semi quantitative and subjective. It still cannot replace liver biopsy for the evaluation of HCC.

This study is aimed to quantify the image characters of B-mode image and the scatterer properties using Nakagami distribution. Nakagami parameter is a general model to describe the distribution of scatterers. Therefore, the investigators hypothesized that Nakagami parameter may also reflect the histological changes in different grades of HCC.

In this study, the resected HCC tumor samples will be collected from the participants who are going to receive surgical resection, and the tumor US images and Nakagami values will be obtained via the single-element ultrasound system. The correlation between the ultrasound backscatter parameter and the differentiation grade will be analyzed.

Histological Differentiation Grade Predicted by Ultrasound Backscatterer Imaging

Suspected recurrences will be confirmed by CT or MRI.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Comparing Re-TACE Versus SABR for Post-prior-TACE Incompletely Regressed HCC: a Randomized Controlled Trial (TASABR)	NCT02921139	Hepatocellular ...	Stereotactic ab... Re-Transcathete...	20 Years -	Dalin Tzu Chi General Hospital
Early Detection of Hepatocellular Carcinoma in a High-risk Prospective Cohort (ELEGANCE)	NCT04965259	Liver Diseases		40 Years - 90 Years	National Cancer Centre, Singapore
CAR-T Cell Immunotherapy for HCC Targeting GPC3	NCT02723942	GPC3 Positive H... CAR-T Cell Immu...	CAR-T cell immu...	18 Years - 70 Years	Fuda Cancer Hospital, Guangzhou
Comparing Re-TACE Versus SABR for Post-prior-TACE Incompletely Regressed HCC: a Randomized Controlled Trial (TASABR)	NCT02921139	Hepatocellular ...	Stereotactic ab... Re-Transcathete...	20 Years -	Dalin Tzu Chi General Hospital
Histological Differentiation Grade Predicted by Ultrasound Backscatterer Imaging	NCT02786199	Neoplastic Dise... Pathology		20 Years - 75 Years	National Taiwan University Hospital
Early Detection of Hepatocellular Carcinoma in a High-risk Prospective Cohort (ELEGANCE)	NCT04965259	Liver Diseases		40 Years - 90 Years	National Cancer Centre, Singapore

Spots Global Cancer Trial Database for hepatocellular carcinoma(hcc)