Gastric Cancer Early Detection by Multi-dimensional Analysis of cfDNA

Development and Validation of a Blood-based Assay for Gastric Cancer Early Detection Using Multi-dimensional Analysis of Cell Free DNA Whole Methylome Sequencing-Protocol for an Observational, Case-control Study

To facilitate the early gastric cancer diagnosis, an assay based on assessing large-scale methylation and fragmentation profiles of the plasma cell free (cfDNA) will be developed and validated.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Genetic: whole genomic methylation and fragmentation profile analysis of cfDNA

Detailed Description

Cancer-related features in cell-free DNA (cfDNA) fragments have gradually been identified and play essential roles for non-invasive early cancer detection. Integrated analysis of several cfDNA features have proven to achieve enhanced detection sensitivity as compared to single feature.

This study aims to develop and validate a novel blood-based whole methylome sequencing followed with a multi-dimensional model to analyze several features of cfDNA for GC early detection. Specifically, blood samples will be prospectively collected before gastroscopy. Cases and controls will be randomly divided into a training and a testing dataset at a ratio of 2:1. Plasma cfDNA will be isolated and extracted, followed with a bisulfite-free low-depth whole methylome sequencing. A multi-dimensional model named THorough Epigenetic Marker Integration Solution (THEMIS) including methylation, fragmentation, and chromosomal copy number alternation will be constructed in the training dataset. The performance of the model in differentiating cancer patients from non-cancer controls will then be evaluated in the testing dataset.

• Study Type: Observational
• Enrollment (Anticipated): 360

Contacts and Locations

• Study Contact: Name: Ning Shen; Phone Number: 400-080-0660; Email: shen.ning1@genecast.com.cn
• Study Contact Backup: Name: Yulong Li; Email: li.yulong@genecast.com.cn

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China
      • Recruiting
      • The First Affiliated Hospital of Air Force Military Medical University (Xijing Hospital)
      • Contact: Gang Ji; Phone Number: 13572152581; Email: Jigang@fmmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This study will enroll about 360 individuals who receive gastroscopy in The First Affiliated Hospital of Air Force Military Medical University (Xijing Hospital), Xi'an, Shaanxi province, China.

Two groups will be formed based on gastroscopy results, malignant group and non-malignant group. The malignant group includes patients diagnosed with high grade Intraepithelial neoplasia or GC (> 50% of patients in stage I and II) while the non-malignant group contains healthy individuals and patients with non-atrophic gastritis, gastric ulcer, gastric polyp or other benign gastric diseases.

Description

Inclusion Criteria:

1. Complete clinical info;
2. Patients self-agree to join the study and with signed patient consent and good compliance.

The specific inclusion criteria for subjects to be included in the malignant group:

1. According to the definition of AJCC's 8th Edition Cancer Staging Manual, patients with gastric adenocarcinoma confirmed by histopathology and with pathological stages of stage I-IV, including patients with esophageal gastric junction adenocarcinoma (EGJ);
2. Has not previously received any local or systematic anti-tumor treatment.

Exclusion Criteria:

1. Diagnosed previously with any kind of malignant tumor;
2. Have received total or partial gastrectomy;
3. Have received bone marrow or organ transplantation;
4. Have received blood transfusion in the past 6 months;
5. Incomplete clinical info or unqualified to participate in the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
malignant group; patients diagnosed with high grade Intraepithelial neoplasia or GC (> 50% of patients in stage I and II)	Genetic: whole genomic methylation and fragmentation profile analysis of cfDNA; The assay for gastric cancer early detection will be built based on low-depth methylone sequencing followed with a multi-dimensional model construction with analysing several features such as methylation, fragmentation, and chromosomal copy number alternation.
non-malignant group; healthy individuals and patients with non-atrophic gastritis, gastric ulcer, gastric polyp or other benign gastric diseases	Genetic: whole genomic methylation and fragmentation profile analysis of cfDNA; The assay for gastric cancer early detection will be built based on low-depth methylone sequencing followed with a multi-dimensional model construction with analysing several features such as methylation, fragmentation, and chromosomal copy number alternation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The performance of each single feature and the ensemble model with integrated features for early GC detection	The efficacy of each single feature-based model and the ensemble model comparing with pathologic diagnostic results, the gold standard, and gastroscope diagnosis, including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).	18 months
The performance of each single feature and the ensemble model with integrated features for early GC detection in each clinical stage	The efficacy of each single feature-based model and the ensemble model comparing with pathologic diagnostic results, the gold standard, and gastroscope diagnosis, including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The performance of the ensemble model in combination of possible GC related biomarkers such as PG, G17, and/or Hp levels for early GC detection	The efficacy of the integrated model comparing with pathologic diagnostic results, the gold standard, and gastroscope diagnosis, including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).	18 months

Collaborators and Investigators

• Sponsor: GeneCast Biotechnology Co., Ltd.
• Collaborators: The First Affiliated Hospital of Air Force Military Medical University (Xijing Hospital)
• Investigators: Principal Investigator: Gang Ji, The First Affiliated Hospital of Air Force Military Medical University (Xijing Hospital), Xi'an, China

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Anticipated): March 31, 2024
• Study Completion (Anticipated): March 31, 2024

Study Registration Dates

• First Submitted: December 12, 2022
• First Submitted That Met QC Criteria: December 25, 2022
• First Posted (Actual): December 30, 2022

Study Record Updates

• Last Update Posted (Actual): December 30, 2022
• Last Update Submitted That Met QC Criteria: December 25, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: D-P200110-MCCGW-HP-7-GC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No