Clinical trial NCT05626985: Refinement and Validation of a Diagnostic Model (GAMAD) for Early Detection of Hepatocellular Carcinoma
Official title: Refinement and Validation of a Comprehensive Clinical Diagnostic Model (GAMAD) for Early Detection of Hepatocellular Carcinoma: A Multicenter, Prospective Study Protocol
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hepatocellular Carcinoma
Keywords: early detection
Lead sponsor: Singlera Genomics Inc.
Sponsor class: INDUSTRY
Collaborators: name: The First Hospital of Jilin University
First posted: 2022-11-25
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients must have baseline evaluations performed prior to the study and must meet all inclusion and exclusion criteria. In addition, the patient must be thoroughly informed about all aspects of the study, including the study visit schedule and required evaluations and all regulatory requirements for informed consent. The written informed consent must be obtained from the patient prior to enrollment. The following criteria apply to all patients enrolled onto the study unless otherwise specified

Brief summary: Most hepatocellular carcinoma (HCC) cases were at advanced stage when diagnosis established. This study is intended to establish a clinical diagnostic model GAMAD for early-stage HCC and evaluate the diagnostic efficiency the same time. This study is a multicenter prospective study. Participants including healthy control,HCC, liver cirrhosis, hepatitis and benign tumor-like lesions are consecutively recruited into the cohort. All the blood samples are collected before any treatments and will be tested in single center in order to decrease bias.

Detailed description: GALAD score including age, sex, PIVKA-II(DCP), Alpha-fetoprotein (AFP) and alpha-fetoprotein L3 (AFP-L3), is a serum biomarker-based panel that can aid in early detection among patients with a high risk for liver cancer. While increasing studies showed the diagnostic accuracy of AFP-L3 was not as good as that of AFP or PIVKA-II, and AFP-L3 was not significant in the multivariable model. Thus, a model with better diagnostic accuracy and more suitable for Chinese patients is needed. Here, based on a multi-locus blood-based assay targeting circulating tumor DNA methylation, we aim to develop a novel diagnostic model--GAMAD (gender, age, methylation, AFP and DCP) and validate its performance among HCC patients and those at high risk of developing HCC,such as liver cirrhosis, hepatitis patients. This is a multicenter, observational, prospective study. After giving fully informed consent, the participants will undergo the regular treatment according to NCCN guidelines.

Eligibility criteria: Inclusion Criteria:

* Age above 18
* Establishing Diagnosis according to the European Association for the Study of Liver(EASL) criteria
* High risk group of developing HCC including liver cirrhosis and hepatitis under the confirmed diagnosis
* Able to provide sufficient and qualified blood samples for study tests
* No prior or undergoing cancer treatment (local or systematic)
* Able to provide a written informed consent

Exclusion Criteria:

* Obstructive jaundice patients
* Medical history of taking warfarin
* With other known malignant tumors or multiple primary tumors
* Patients with autoimmune diseases, genetic diseases, mental diseases/ disabilities and other diseases considered unsuitable for the study by the investigator
* During pregnancy or lactation
* Recipient of blood transfusion within 3 months prior to study blood draw
* Insufficient qualified blood sample for study test

Primary outcomes:
measure: GAMAD
timeFrame: Day one
Secondary outcomes:
measure: GALAD
timeFrame: Day one
measure: circulating tumor DNA methylation
timeFrame: Day one
Other outcomes:
Locations:
city: Jilin
country: China
facility: The First Hospital of Jilin University
city: Shanghai
country: China
facility: Eastern Hepatobiliary Surgery Hospital
city: Tianjin
country: China
facility: Tianjin Third Central Hospital
Study officials:
affiliation: Eastern Hepatobiliary Surgery Hospital
name: Tian Yang, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Hospital of Jilin University
name: Guoyue Lv, Ph.D
role: STUDY_CHAIR
affiliation: Tianjin Third Central Hospital
name: Fengmei Wang
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yang T, Xing H, Wang G, Wang N, Liu M, Yan C, Li H, Wei L, Li S, Fan Z, Shi M, Chen W, Cai S, Pawlik TM, Soh A, Beshiri A, Lau WY, Wu M, Zheng Y, Shen F. A Novel Online Calculator Based on Serum Biomarkers to Detect Hepatocellular Carcinoma among Patients with Hepatitis B. Clin Chem. 2019 Dec;65(12):1543-1553. doi: 10.1373/clinchem.2019.308965. Epub 2019 Oct 31.
citation: Liu S, Sun L, Yao L, Zhu H, Diao Y, Wang M, Xing H, Lau WY, Guan M, Pawlik TM, Shen F, Xu M, Tong X, Yang T. Diagnostic Performance of AFP, AFP-L3, or PIVKA-II for Hepatitis C Virus-Associated Hepatocellular Carcinoma: A Multicenter Analysis. J Clin Med. 2022 Aug 29;11(17):5075. doi: 10.3390/jcm11175075.