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

NCT ID: NCT05431621

Last Updated: 2025-01-29

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 2430 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-11-15
• Study Completion Date: 2023-07-31

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.

Detailed Description

Design of the project: 1) Participants who sign informed consent forms will complete the disease history information collection;2) Collect samples of cancer tissue and corresponding paracancer samples, as well as peripheral blood; 3) Using the MONOD patent detection data of the company's previous research and combining with literature retrieval, to analyze the tissue samples of digestive system cancers to screen the methylation mutation sites;4) ctDNA methylation markers are preliminarily screened by plasma of healthy persons paired with tissues;5) Using the screened blood ctDNA specific methylation markers together with other molecular markers to establish a targeted detection method for early digestive system cancer lesions;6) Retain the most distinguishing targets in the original panel test and establish the second version of the panel;7) Establish and validate predictive models to finalize multitype molecular target detection for peripheral blood DNA;8) Construct statistical learning models based on ctDNA methylation and fragment features, miRNA7™ and CTC, and optimize the models respectively;9) Evaluate the sensitivity and specificity of the models in cancer early detection.

Conditions

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

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

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.

No interventions assigned to this group

Negative group

985 healthy individuals.

No interventions assigned to this group

High risk group

410 cases with precancerous diseases.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

1. Aged 18 to 80, no gender limitation, no pregnant or breastfeeding for women;

2. Those who can accept gastroscopy and/or total colonoscopy;

3. Newly-diagnosed patients who had not received surgery, radiotherapy, chemotherapy, targeted therapy or other anti-tumor intervention;

4. Stop anticoagulant drugs such as warfarin, aspirin, and bolivir for 1 week, and stop low molecular weight heparin that day;

5. No previous history of other tumor diseases, and no abnormalities in the liver and kidney;

6. No major trauma requiring blood transfusion treatment within one week.

1. 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;

2. 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;

3. 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;

4. 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.

Exclusion Criteria

1. Previous esophageal cancer, stomach cancer, bowel cancer and gastrointestinal adenoma;

2. Have a history of other cancers;

3. Systemic inflammatory response syndrome;

4. Previously experienced esophageal, gastric or colorectal adenoma removal or tumor resection;

5. Patients with Lynch syndrome in the family;

6. A history of severe cardiovascular disease (e.g., previous myocardial infarction, coronary artery bypass grafting, coronary stenting, congestive heart failure, myocardial infarction within 6 months, or uncontrolled severe hypertension, etc.) who were deemed unsuitable for inclusion by the investigator;

7. Have participated in an "interventional" clinical trial within the past 30 days and have taken the experimental drug;

8. Unsuitable for this trial determined by the researchers;

9. Failure to collect blood on time according to plan;

10. The blood sample does not meet the requirements.

Hepatocellular Carcinoma Group

1. Patients with liver cancer who have received surgery, radiotherapy, chemotherapy, targeted therapy;

2. Cancer patients except HCC, or patients with liver metastasis;

3. Systemic inflammatory response syndrome;

4. A history of severe cardiovascular disease (e.g., previous myocardial infarction, coronary artery bypass grafting, coronary stenting, congestive heart failure, myocardial infarction within 6 months, or uncontrolled severe hypertension, etc.) who were deemed unsuitable for inclusion by the investigator;

5. Have participated in an "interventional" clinical trial within the past 30 days and have taken the experimental drug;

6. Unsuitable for this trial determined by the researchers;

7. Failure to collect blood on time according to plan;

8. The blood sample does not meet the requirements.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Xuhui Central Hospital, Shanghai

OTHER

Sponsor Role: collaborator

Changhai Hospital

OTHER

Sponsor Role: collaborator

Hubei Cancer Hospital

OTHER

Sponsor Role: collaborator

Shanghai Public Health Clinical Center

OTHER_GOV

Sponsor Role: collaborator

Singlera Genomics Inc.

INDUSTRY

Sponsor Role: collaborator

Shanghai Zhongshan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jian Zhou, Doctor

Role: STUDY_DIRECTOR

Fudan University

Yunshi Zhong, Doctor

Role: STUDY_DIRECTOR

Fudan University

Rui Liu, Doctor

Role: PRINCIPAL_INVESTIGATOR

Singlera Genomics Inc.

Bin Yan, Doctor

Role: STUDY_DIRECTOR

Shanghai Zhongshan Hospital

Dongli He, Master

Role: STUDY_DIRECTOR

Xuhui Central Hospital, Shanghai

Locations

Xuhui Central Hospital, Shanghai

Shanghai, Shanghai Municipality, China

Zhongshan Hospital of Fudan University

Shanghai, Shanghai Municipality, China

Shanghai Public Health Clinical Center

Shanghai, Shanghai Municipality, China

Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, China

Countries

China

References

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.

Reference Type: BACKGROUND

PMID: 28263317 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32694610 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 40468355 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38741204 (View on PubMed)

Other Identifiers

2019YFC1315802-01

Identifier Type: -

Identifier Source: org_study_id