Development of Free DNA Multi-target Methylated PCR for Auxiliary Diagnosis of Gastric Cancer

• ClinicalTrials.gov Identifier: NCT05336058
• Recruitment Status: Recruiting
• First Posted: April 20, 2022
• Last Update Posted: April 20, 2022
• Sponsor: Singlera Genomics Inc.
• Collaborator: Fudan University
• Information provided by (Responsible Party): Singlera Genomics Inc.

Study Description

Brief Summary:

This was a case control, non-intervention study jointly developed by Fudan University Cancer Hospital and Shanghai Singlera Genomics Company. The enrolled population was screened by gastric surgery, including gastric cancer, precancerous lesions, benign lesions, and healthy control group. 10ml of whole blood of the enrolled subjects was collected for multi-target PCR detection of cfDNA methylation. The objective is to explore the clinical performance of polygene methylation (PCR-fluorescence probe) in the adjunctive diagnosis of gastric cancer, including the sensitivity of detection of various types and stages of gastric cancer, the specificity of detection of healthy controls, precancerous states, precancerous lesions, and the detection interference of other cancers. The diagnostic performance will be compared with CA199, CEA and CA724. The research data will provide a basis for screening targets for the development of detection kits.

Condition or disease	Intervention/treatment
Stomach Cancer	Other: No intervention

Detailed Description:

Design and plan of the project: 1) Using the MONOD patent detection data of the company's previous research and combining with literature retrieval, analyze the tissue samples of gastric cancer of different stages and their paired paracancer tissues to screen the methylation mutation sites related to early gastric cancer and select the sites suitable for PCR detection; 2) ctDNA methylation markers in gastric cancer blood were preliminarily screened by plasma of healthy persons and preoperative plasma paired with tissues; 3) Using the screened blood ctDNA specific methylation markers, a targeted detection method for early gastric cancer lesions was designed; 4) The detection performance of the independent validation set sample confirmation establishment method.

Study Design

• Study Type: Observational
• Estimated Enrollment: 1240 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: A Case-control, Non-intervention Study for Gastric Cancer Screening
• Actual Study Start Date: February 1, 2022
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2022

Groups and Cohorts

Group/Cohort	Intervention/treatment
Gastric cancer group; A total of about 500 cases are expected to be enrolled, including 150 cases in stage I and 100 cases in II-IV. Pathological diagnosis is required.	Other: No intervention; In this non-intervention study, 10ml of whole blood of enrolled subjects was collected for multi-target PCR detection of cfDNA methylation.
Negative group; A total of about 740 cases were included, including 400 cases without abnormal gastroscopy, 100 cases with other cancers, and 240 cases with precancerous gastric cancer and other lesions.	Other: No intervention; In this non-intervention study, 10ml of whole blood of enrolled subjects was collected for multi-target PCR detection of cfDNA methylation.

Outcome Measures

Primary Outcome Measures :

1. Sensitivity and specificity of methylation detection in gastric cancer [ Time Frame: assessed up to 12 months ]
   To investigate the sensitivity and specificity of polygene methylation in the diagnosis of gastric cancer of different types and stages, and to evaluate its value as an auxiliary diagnosis.
2. Comparison of polygene methylation detection and other serological detection methods in gastric cancer [ Time Frame: assessed up to 12 months ]
   The specificity and sensitivity of multigene methylation (PCR-fluorescence probe) and CA199, CEA and CA724 in the auxiliary diagnosis of gastric cancer were compared.
3. Screening of genetic targets for kit development [ Time Frame: assessed up to 12 months ]
   The research data will provide a basis for screening gene targets for the development of subsequent detection kits.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Eligible participants were recruited from the Department of Gastrosurgery, Fudan University Cancer Hospital, including gastric cancer, precancerous lesions of gastric cancer, other gastric lesions, no abnormalities in gastroscopy, and other cancers.

Criteria

Inclusion Criteria:

1. At least 18 years of age, no gender limitation;
2. those who can accept gastroscopy or provide pathological examination results of postoperative gastric biopsy
3. Patients newly diagnosed with stage I-IV gastric adenocarcinoma who had not received surgery, radiotherapy, chemotherapy, targeted therapy or other anti-tumor intervention before blood collection;
4. There were precancerous lesions and carcinoma in situ in the pathological examination of gastroscopy or esophageal biopsy, and no abnormalities in other gastric lesions, gastroscopy or other cancers. And no previous history of tumor disease.

Exclusion Criteria:

1. Previous digestive system tumors, including gastric cancer, esophageal cancer, colorectal cancer, liver cancer, etc.;
2. have a history of other cancers and have not been clinically cured (clinically cured: no recurrence and metastasis within 5 years after surgery);
3. Systemic inflammatory response syndrome;
4. A history of severe cardiovascular disease (e.g., previous myocardial infarction, coronary artery bypass grafting, or coronary stenting); A history of congestive heart failure; Patients with myocardial infarction within 6 months, uncontrolled severe hypertension, etc.) who were deemed unsuitable for inclusion by the investigator;
5. Those who have received major surgical treatment such as blood transfusion or transplantation within 3 months
6. Participants in other interventional clinical researchers, pregnant or lactating women, or patients with autoimmune diseases, genetic diseases, mental diseases, etc., within 3 months.
7. have participated in an "interventional" clinical trial within the past 30 days and have taken the experimental drug;
8. patients with other diseases deemed unsuitable for inclusion by the investigator;

Contacts and Locations

Contacts

Contact: Dazhi Xu, PhD; +8618221073033; xudzh@shca.org.cn

Contact: Jing Guo, PhD; gjsysu@126.com

Locations

China, Shanghai

Fudan University Cancer Hospital; Recruiting

Shanghai, Shanghai, China, 200000

Contact: Jing Guo +8618221073033 gjsysu@126.com

Sponsors and Collaborators

Singlera Genomics Inc.

Fudan University

Investigators

• Principal Investigator: Rui Liu, PhD; Singlera Genomics Inc.

More Information

Publications:

Yu G, Wang GX, Wang HG, Mo FF, Tang BB. The value of detecting pepsinogen and gastrin-17 levels in serum for pre-cancerous lesion screening in gastric cancer. Neoplasma. 2019 Jul 23;66(4):637-640. doi: 10.4149/neo_2018_180825N647. Epub 2019 Apr 24.

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.

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.

• Responsible Party: Singlera Genomics Inc.
• ClinicalTrials.gov Identifier: NCT05336058
• Other Study ID Numbers: 2201249-17
• First Posted: April 20, 2022
• Last Update Posted: April 20, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Singlera Genomics Inc.:

DNA methylation; Early gastric cancer screening

Additional relevant MeSH terms:

Stomach Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases