Establishment of Molecular Classification Models for Early Diagnosis of Digestive System Cancers

NCT05431621 | Completed

• 1 other identifier: 2019YFC1315802-01
• Study Type: observational
• Target: 2,430
• Locations: 1 country
• Sites: 4

Brief Summary

This is a single blind, case control, multicenter study jointly developed by Zhongshan Hospital of Fudan University, Shanghai Public Health Clinical Center, Shanghai Xuhui Central Hospital, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, and Shanghai Singlera Genomics Company. The enrolled population will include positive group, precancerous lesions and healthy control group, which is expected to enroll 2,430 participants. The primary objective is to establish molecular testing methods for non-invasive screening and early diagnosis of digestive system cancers through ctDNA methylation and mutation, cfDNA and ctDNA fragment size, and end motif based model (for esophageal, gastric, colorectal cancer), and through ctDNA methylation detection, ctDNA low-pass WGS, miRNA7 and CTC detection and analysis technology based model (for hepatocellular carcinoma). The sensitivity and specificity of the models in cancer early detection will be evaluated.

Conditions

Esophageal Cancer; Gastric (Stomach) Cancer; Colorectal Cancer; Hepatocellular Carcinoma

Keywords

ctDNA markers; DNA methylation; DNA fragment feature; miRNA; CTC; Cancer early detection

Outcome Measures

Primary Outcomes (2)

• Establish ctDNA-targeted sequencing models for early detection of esophageal, gastric, colorectal and hepatocellular cancer, and evaluate the diagnosis value

  To discover the characteristic targets of ctDNA methylation, fragment, and mutation in esophageal, gastric, colorectal cancers, and hepatocellular carcinoma, and establish the early detection panel. Then, evaluate the sensitivity and specificity of multi-cancer early detection models.

  assessed up to 1 year

• Establish and evaluate the non-invasive early detection model for hepatocellular carcinoma

  To establish and evaluate the early detection model for hepatocellular carcinoma based on ctDNA methylation detection, ctDNA low-pass WGS, miRNA7™ and CTC detection.

  assessed up to 1 year

Study Arms (3)

Digestive system cancer group

A total of about 1035 cases are expected to be enrolled, including 432 cases in stage I and 603 cases in II-IV.

Negative group

985 healthy individuals.

High risk group

410 cases with precancerous diseases.

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study aims to enroll 2430 participants from Zhongshan Hospital, Xuhui central hospitial, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University and Shanghai Public Health Clinical Center.

You may qualify if:

• Aged 18 to 80, no gender limitation, no pregnant or breastfeeding for women;
• Those who can accept gastroscopy and/or total colonoscopy;
• Newly-diagnosed patients who had not received surgery, radiotherapy, chemotherapy, targeted therapy or other anti-tumor intervention;
• Stop anticoagulant drugs such as warfarin, aspirin, and bolivir for 1 week, and stop low molecular weight heparin that day;
• No previous history of other tumor diseases, and no abnormalities in the liver and kidney;
• No major trauma requiring blood transfusion treatment within one week.

You may not qualify if:

• Previous esophageal cancer, stomach cancer, bowel cancer and gastrointestinal adenoma;
• Have a history of other cancers;
• Systemic inflammatory response syndrome;
• Previously experienced esophageal, gastric or colorectal adenoma removal or tumor resection;
• Patients with Lynch syndrome in the family;
• Have participated in an "interventional" clinical trial within the past 30 days and have taken the experimental drug;
• Unsuitable for this trial determined by the researchers;
• Failure to collect blood on time according to plan;
• The blood sample does not meet the requirements.
• Hepatocellular Carcinoma Group
• Applicable to all enrolled volunteers (1) Aged 18 to 80, no gender limitation, no pregnant or breastfeeding for women; (2) No previous history of malignancy in other sites; (3) To avoid the risk of bleeding caused by taking anticoagulants during sampling, the following provisions shall be made according to different types of samples: stop anticoagulant drugs such as warfarin, aspirin, and bolivir for 1 week, and stop low molecular weight heparin that day; the doctor in charge decides whether to stop anticoagulant drugs before blood draw, according to the specific situation of the volunteers, ; (4) No major trauma requiring blood transfusion treatment within one week;
• Only for patients with hepatocellular carcinoma (HCC). (1) Diagnosed with stage I-IV hepatocellular carcinoma; (2) Newly-diagnosed patients with liver cancer, who had not received surgery, radiotherapy, chemotherapy, targeted therapy or other anti-tumor intervention;
• Only for high-risk groups (1) Diagnosis of child-Pugh grade A or B, chronic hepatitis B or cirrhosis; (2) No history of liver cancer or malignancy in other sites;
• For healthy people only (1) Normal liver function test results on the day of blood collection; (2) No history of hepatitis B, hepatitis C and cirrhosis; (3) No history of liver cancer or malignancy in other sites.
• Patients with liver cancer who have received surgery, radiotherapy, chemotherapy, targeted therapy;

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead
• Xuhui Central Hospital, Shanghai: collaborator
• Changhai Hospital: collaborator
• Hubei Cancer Hospital: collaborator
• Shanghai Public Health Clinical Center: collaborator
• Singlera Genomics Inc.: collaborator

Study Sites (4)

Xuhui Central Hospital, Shanghai

Shanghai, Shanghai Municipality, 200030, China

Location

Zhongshan Hospital of Fudan University

Shanghai, Shanghai Municipality, 200030, China

Location

Shanghai Public Health Clinical Center

Shanghai, Shanghai Municipality, 201500, China

Location

Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, 201700, China

Location

Related Publications (4)

• Guo S, Diep D, Plongthongkum N, Fung HL, Zhang K, Zhang K. Identification of methylation haplotype blocks aids in deconvolution of heterogeneous tissue samples and tumor tissue-of-origin mapping from plasma DNA. Nat Genet. 2017 Apr;49(4):635-642. doi: 10.1038/ng.3805. Epub 2017 Mar 6.

  PMID: 28263317 BACKGROUND

• Chen X, Gole J, Gore A, He Q, Lu M, Min J, Yuan Z, Yang X, Jiang Y, Zhang T, Suo C, Li X, Cheng L, Zhang Z, Niu H, Li Z, Xie Z, Shi H, Zhang X, Fan M, Wang X, Yang Y, Dang J, McConnell C, Zhang J, Wang J, Yu S, Ye W, Gao Y, Zhang K, Liu R, Jin L. Non-invasive early detection of cancer four years before conventional diagnosis using a blood test. Nat Commun. 2020 Jul 21;11(1):3475. doi: 10.1038/s41467-020-17316-z.

  PMID: 32694610 BACKGROUND

• Huang A, Guo DZ, Su ZX, Zhong YS, Liu L, Xiong ZG, He DL, Yan B, Li QL, Feng Z, Wang WQ, Lu PX, He MJ, Qi ZP, Guo Q, Cheng JW, Zhang SY, Guo W, Li Q, Lin GY, Sun HC, Qiu SJ, He QY, Fan J, Goel A, Liu R, Jin G, Yang XR, Zhou J. GUIDE: a prospective cohort study for blood-based early detection of gastrointestinal cancers using targeted DNA methylation and fragmentomics sequencing. Mol Cancer. 2025 Jun 5;24(1):163. doi: 10.1186/s12943-025-02367-x.

  PMID: 40468355 DERIVED

• Guo DZ, Huang A, Wang YC, Zhou S, Wang H, Xing XL, Zhang SY, Cheng JW, Xie KH, Yang QC, Ma CC, Li Q, Chen Y, Su ZX, Fan J, Liu R, Liu XL, Zhou J, Yang XR. Early detection and prognosis evaluation for hepatocellular carcinoma by circulating tumour DNA methylation: A multicentre cohort study. Clin Transl Med. 2024 May;14(5):e1652. doi: 10.1002/ctm2.1652.

  PMID: 38741204 DERIVED

MeSH Terms

Conditions

Esophageal Neoplasms; Stomach Neoplasms; Colorectal Neoplasms; Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Liver Diseases

Study Officials

• Jian Zhou, Doctor

  Fudan University

  STUDY DIRECTOR

• Yunshi Zhong, Doctor

  Fudan University

  STUDY DIRECTOR

• Rui Liu, Doctor

  Singlera Genomics Inc.

  PRINCIPAL INVESTIGATOR

• Bin Yan, Doctor

  Shanghai Zhongshan Hospital

  STUDY DIRECTOR

• Dongli He, Master

  Xuhui Central Hospital, Shanghai

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2022
• First Posted: June 24, 2022
• Study Start: November 15, 2020
• Primary Completion: June 30, 2023
• Study Completion: July 31, 2023
• Last Updated: January 29, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)