Clinical trial NCT05668910: Gastric Cancer Early Detection by Multi-dimensional Analysis of cfDNA
Official title: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Gastric Cancer
Lead sponsor: GeneCast Biotechnology Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: The First Affiliated Hospital of Air Force Medicial University
First posted: 2022-12-30
Enrollment: 360
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The performance of each single feature and the ensemble model with integrated features for early GC detection
timeFrame: 18 months
measure: The performance of each single feature and the ensemble model with integrated features for early GC detection in each clinical stage
timeFrame: 18 months
Secondary outcomes:
measure: 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
timeFrame: 18 months
Other outcomes:
Locations:
city: Xi'an
country: China
facility: The First Affiliated Hospital of Air Force Military Medical University (Xijing Hospital)
state: Shaanxi
Study officials:
affiliation: The First Affiliated Hospital of Air Force Military Medical University (Xijing Hospital), Xi'an, China
name: Gang Ji
role: PRINCIPAL_INVESTIGATOR
References: