Circulating Biomarker Signatures for the Detection of Gastric Preneoplasia and Cancer

Gastric Cancer Clinical Trial

— PREGASIGN#1  

Official title:

Circulating Biomarker Signatures for the Detection of Gastric Preneoplasia and Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05854368
• Other study ID #: 2021-097
• Status: Recruiting
• Phase: N/A
• Start date: July 3, 2023
• Est. completion date: July 2025

Study information

• Verified date: July 2023
• Source: Institut Pasteur
• Contact: Eliette TOUATI, PhD
• Phone: +33140613785
• Email: eliette.touati[@]pasteur.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to characterize and validate a signature of circulating biomarkers in plasma, associated with the presence of gastric preneoplasia in patients with preexisting gastric lesion compared with a control group.

For this purpose:

• Patients with pre-existing gastric lesions will be invited to participate to this study. If they are willing to participate an additional blood sample (10mL) will be collected at the time of the blood collection performed during their routine care

• Healthy subjects will be invited to participate to constitute the control group. If they are willing to participate a blood sample (10 ml) will be drawn specifically for this study

Description:

Gastric cancer (GC) is the fourth cause of cancer-related death and the fifth most common diagnosed cancer worldwide with 1 million new cases per year. GC is mainly associated with a poor prognosis, highlighting the importance of its early detection. GC results from a multistep process starting from a gastric chronic inflammation preceding atrophic gastritis (AG), the development of preneoplasia (intestinal metaplasia (IM), dysplasia (Dys) and then cancer lesions. Presently, GC can only be diagnosed by endoscopy, which is an invasive, and costly method with its limits. Indeed, preneoplasia as Dys can escape endoscopic detection. Therefore, the discovery of blood-based biomarkers to identify the presence of gastric preneoplasia and/or cancer lesions at the earliest, at an asymptomatic stage, is of paramount interest. It is crucial not only for the early detection/prevention of individuals at risk of GC but also useful for patient follow-up to predict disease recurrence/outcome and to monitor treatment. Using plasma samples from patients at various stages of the GC cascade, we previously identified two signatures of 6 protein candidates to predict the presence of preneoplasia and GC lesions. Based on these data, the goal of this study is to further test and validate these different signatures, and to improve their predictive ability at the earliest stages of the GC cascade, taking into account the different types of gastric preneoplasia, IM and Dys, and their grade of severity. To achieve this goal, a large multicentric cohort of patients will be established including different groups of plasma samples covering the most complete panel of the type/grades of gastric preneoplasia as well as at early stages of GC. These plasma samples will be then used to measure the level of the different signature components using various method of analysis as immuno-based assays.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2500
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Common

• 18 years old or highter

• written informed consent prior to any study procedure

• Affiliated to a social insurance system

Specific to patients with gastric lesions

• Untreated glandular atrophy (with or without intestinal metaplasia and/or dysplasia) and histologically diagnosed as of 2014

• Treatment naïve Gastric cancer (distal or proximal adenocarcinoma)

Exclusion Criteria:

Common

• Autoimmune disease or disease that impacts the immune system (e.g: HIV)

• Chronic inflammatory disease

• Known evolutive cancer (excluding gastric cancer)

• Treated in the last 3 months or currently treated with therapy that interferes with the immune system (e.g. immunosuppressive therapy)

• Current treatment with long-term corticosteroid therapy

• Current treatment with long-term nonsteroidal anti-inflammatory drugs

• Pregnant woman or breastfeeding

• Patient or healthy volunteer under legal protection (e.g. guardianship)

• Patient or healthy volunteer currently participating to a clinical trial evaluating either an experimental medical product or a medical device

• Patient or healthy volunteer currently in custody

Specific to Healthy Volunteer

• Known history of Helicobacter pylori infection

• Known history of gastric lesions (i.e. chronic gastritis, gastric atrophy, intestinal metaplasia, dysplasia and cancer)

Related Conditions & MeSH terms

• Gastric Cancer
• Gastric Lesion
• Gastric Precancerous Condition
• Precancerous Conditions
• Stomach Neoplasms

Intervention

Procedure:
• Additional blood collection as part of routine care
Collection of an additional blood volume (10mL) as part of a blood sampling performed during routine care
• Blood collection
Blood sample collection (10 mL)

Locations

Country	Name	City	State
France	Ambroise Paré Teaching Hospital (AP-HP)	Boulogne-Billancourt
France	Beaujon Teaching Hospital (AP-HP)	Clichy
France	Kremlin Bicêtre Teaching Hospital (AP-HP)	Le Kremlin-Bicêtre
France	Cochin Teaching Hospital (AP-HP)	Paris
France	ICAReB - Investigation clinique (Institut Pasteur)	Paris
France	Saint Antoine Teaching Hospital (AP-HP)	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Institut Pasteur	Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (1)

Kotilea K, Bontems P, Touati E. Epidemiology, Diagnosis and Risk Factors of Helicobacter pylori Infection. Adv Exp Med Biol. 2019;1149:17-33. doi: 10.1007/5584_2019_357. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Characterization and validation of a signature combining plasmatic proteins related to inflammation and carcinogenesis process, associated with the presence of gastric mucosal dysplasia lesions compared with an H. pylori negative control group.	From the plasma obtained from patients previously diagnosed by gastric endoscopy for the presence of dysplasia in the gastric mucosa and that have signed a prior consent form, the concentration of protein biomarker candidates will be determined using a bead-based immunoassay according to Luminex® technology. It will be expressed as amount per ml of plasma. For each protein constituting the signature of biomarkers, its levels in the plasma of patients with dysplasia will be compared to the corresponding levels in healthy subjects with a negative H. pylori serology and referred as a control group.	24 months
Secondary	Characterization and validation of a signature combining plasmatic proteins related to inflammation and carcinogenesis process, associated with the presence of glandular atrophy lesions compared with an H. pylori negative control group.	From the plasma obtained from patients previously diagnosed by gastric endoscopy for the presence of glandular atrophy lesions in the gastric mucosa and that have signed a prior consent form, the concentration of protein biomarker candidates will be determined using a bead-based immunoassay according to Luminex® technology. It will be expressed as amount per ml of plasma. For each protein constituting the signature of biomarkers , its levels in the plasma of patients with gastric glandular atrophy lesions will be compared to the corresponding levels in healthy subjects with a negative H. pylori serology and referred as a control group.	24 months
Secondary	Characterization and validation of a signature combining plasmatic proteins related to inflammation and carcinogenesis process, associated with the presence of intestinal metaplastic lesions compared with an H. pylori negative control group.	From the plasma obtained from patients previously diagnosed by gastric endoscopy for the presence of intestinal metaplastic lesions within the gastric mucosa and that have signed a prior consent form, the concentration of protein biomarker candidates will be determined using a bead-based immunoassay according to Luminex® technology. It will be expressed as amount per ml of plasma. For each protein constituting the signature of biomarkers, its levels in the plasma of patients with gastric intestinal metaplastic lesions will be compared to the corresponding levels in healthy subjects with a negative H. pylori serology and referred as a control group.	24 months
Secondary	Characterization and validation of a signature combining plasmatic proteins related to inflammation and carcinogenesis process, associated with the presence of proximal gastric adenocarcinoma compared with an H. pylori negative control group.	From the plasma obtained from patients previously diagnosed by gastric endoscopy for the presence of proximal gastric adenocarcinoma and that have signed a prior consent form, the concentration of protein biomarker candidates will be determined using a bead-based immunoassay according to Luminex® technology. It will be expressed as amount per ml of plasma. For each protein constituting the signature of biomarkers, its levels in the plasma of patients with proximal gastric adenocarcinoma will be compared to the corresponding levels in healthy subjects with a negative H. pylori serology and referred as a control group.	24 months
Secondary	Characterization and validation of a signature combining plasmatic proteins related to inflammation and carcinogenesis process, associated with the presence of distal gastric adenocarcinoma compared with an H. pylori negative control group.	From the plasma obtained from patients previously diagnosed by gastric endoscopy for the presence of distal gastric adenocarcinoma and that have signed a prior consent form, the concentration of protein biomarker candidates will be determined using a bead-based immunoassay according to Luminex® technology. It will be expressed as amount per ml of plasma. For each protein constituting the signature of biomarkers, its levels in the plasma of patients with distal gastric adenocarcinoma will be compared to the corresponding levels in healthy subjects with a negative H. pylori serology and referred as a control group.	24 months
Secondary	Characterization of the plasma levels of the proteins biomarker composing these signatures specific for the different stages of gastric cancer cascade, between the different studied pathology groups	From the plasma obtained from patients previously diagnosed by gastric endoscopy for the presence of gastric lesions at the different stages of the gastric cancer cascade (dysplasia, glandular atrophy, intestinal metaplasia, proximal gastric adenocarcinoma and distal gastric adenocarcinoma), and that have signed a prior consent form, the concentration of protein biomarker candidates will be determined using a bead-based immunoassay according to Luminex® technology. It will be expressed as amount per ml of plasma. For each protein constituting the signature of biomarkers , its plasma levels will be compared between patients from the different groups of gastric lesions dysplasia, glandular atrophy, intestinal metaplasia, proximal gastric adenocarcinoma and distal gastric adenocarcinoma).	24 months