Auxiliary Diagnosis of Liver Nodules Using cfDNA Whole-genome Signatures

Focal Liver Lesions Clinical Trial

— GUIDER  

Official title:

Auxiliary Diagnosis of Liver Nodules Using cfDNA Whole-genome SignatuRes (GUDIER): an Observational Cohort Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05393102
• Other study ID #: 2022-20
• Status: Not yet recruiting
• Start date: May 2022
• Est. completion date: October 2023

Study information

• Verified date: May 2022
• Source: The Second Affiliated Hospital of Chongqing Medical University
• Contact: Hong Ren, MD
• Phone: 13983888786
• Email: renhong0531[@]vip.sina.com.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

As a prospective, multi-center study, GUIDER will recruit 400 liver nodules participants from different provinces and regions across China. Except for cfDNA signatures, serum biomarkers, histopathological biopsy and enhanced MRI will also be performed. The sensitivity and specificity of the cfDNA signature based-model in liver nodules diagnosing will be evaluated.

Description:

Patients with liver nodules will be recruited for 1 year. Peripheral blood samples of all participants will be collected after being informed about the study and potential risks. CfDNA extraction, library construction, and whole genome sequencing will be performed. A machine learning method will be implemented for cfDNA signatures-based model construction at the end of the study. Sensitivity and specificity will be used to evaluate the performance of cfDNA signatures-based model in liver nodules diagnosis.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 400
• Est. completion date: October 2023
• Est. primary completion date: April 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Eighteen years or elder;

• Participants underwent enhanced MRI for the evaluation of liver nodules =5 cm;

• Participants whose platelet count = 50×109/L, prothrombin activity (PTA) = 60%;

• Participants who are willing and able to perform hepatectomy or tissure biopsy.

Exclusion Criteria:

• Participants with different enhancement mode liver nodules that detected by enhanced MRI and without CEUS confirmation;

• Diagnosis of malignant tumors before recruitment;

• Anti-tumor therapy before recruitment ;

• HIV infection;

• Pregnancy;

• Allogenic blood transfusion or cell therapy within 14 days before peripheral blood samples collection;

• Participants with hepatic encephalopathy, hemangioma, ascites, gastrointestinal bleeding, jaundice, liver failure, congestive heart failure, or any other serious diseases that causing organ damage.

• Participants with any other factors that may leading to termination of the study.

Related Conditions & MeSH terms

• Focal Liver Lesions

Intervention

Other:
• No interventions
No interventions

Locations

Country	Name	City	State
China	The 2nd affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong
China	Eastern Hepatobiliary Surgery Hospital	Shanghai	Shanghai

Sponsors (3)

Lead Sponsor	Collaborator
The Second Affiliated Hospital of Chongqing Medical University	Eastern Hepatobiliary Surgery Hospital, Nanfang Hospital of Southern Medical University

Country where clinical trial is conducted

China, 

References & Publications (4)

Chen L, Abou-Alfa GK, Zheng B, Liu JF, Bai J, Du LT, Qian YS, Fan R, Liu XL, Wu L, Hou JL, Wang HY; PreCar Team. Genome-scale profiling of circulating cell-free DNA signatures for early detection of hepatocellular carcinoma in cirrhotic patients. Cell Res. 2021 May;31(5):589-592. doi: 10.1038/s41422-020-00457-7. Epub 2021 Feb 15. — View Citation

Kobayashi M, Ikeda K, Hosaka T, Sezaki H, Someya T, Akuta N, Suzuki F, Suzuki Y, Saitoh S, Arase Y, Kumada H. Dysplastic nodules frequently develop into hepatocellular carcinoma in patients with chronic viral hepatitis and cirrhosis. Cancer. 2006 Feb 1;106(3):636-47. — View Citation

Llovet JM, Chen Y, Wurmbach E, Roayaie S, Fiel MI, Schwartz M, Thung SN, Khitrov G, Zhang W, Villanueva A, Battiston C, Mazzaferro V, Bruix J, Waxman S, Friedman SL. A molecular signature to discriminate dysplastic nodules from early hepatocellular carcinoma in HCV cirrhosis. Gastroenterology. 2006 Dec;131(6):1758-67. Epub 2006 Sep 19. — View Citation

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity of the cfDNA whole-genome signatures based model in liver nodules diagnosis.	Sensitivity is defined as the ratio of positively detected participants in all malignant nodule patients by cfDNA signatures.	Enrollment of the first participant up to 18 months
Primary	Specificity of the cfDNA whole-genome signatures based model in liver nodules diagnosis.	Specificity is defined as the proportion of negatively detected participants in all benign liver nodules patients by cfDNA signatures.	Enrollment of the first participant up to 18 months
Secondary	Specificity of the model that composed of cfDNA signatures, imaging examination,serum protein markers and clinical characteristics in liver nodules diagnosis.	Specificity is defined as the proportion of negatively detected participants in all benign liver nodules patients by the model that composed of cfDNA whole-genome signatures, imaging examination,serum protein markers, and clinical characteristics.	Through study completion,an average of 18 months