Liquid Biopsies for the Personalized Management of Patients With Hereditary Diffuse Gastric Cancer

Not Applicable

Active, not recruiting

• Conditions: Hereditary Diffuse Gastric Cancer
• Interventions: Genetic: Liquid biopsies (blood, gastric fluid).

• Registration Number: NCT04253106
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Activating somatic mutations and methylation profiles identified by liquid biopsies could identify CDH1 and CTNNA1 pathogenic variants carriers with invasive diffuse gastric cancer undetectable by upper G-I endoscopy.

Detailed Description

Carriers of germline pathogenic variants in the CDH1 and CTNNA1 genes have the Hereditary Diffuse Gastric Cancer Syndrome. Asymptomatic carriers have at high lifetime risk of diffuse gastric cancer (30-70%). Screening upper gastrointestinal endoscopy, even with multiple random biopsies, misses signet ring cell cancer foci. Invasive cancers can thus go undetected. There is therefore a recommendation of total risk-reducing gastrectomy, at least in carriers with a family history of gastric cancer. Novel screening strategies are needed. In this pilot project, the investigators will perform liquid biopsies of both blood and gastric fluid in asymptomatic carriers who refuse gastrectomy and in controls. The investigators aim to show that somatic mutations in a panel of genes involved in gastric cancer and methylation profiles are detected in a subset of carriers, and not in controls. These could be indicative of invasive cancer undetected by endoscopy, and would thus be a strong argument for risk-reducing gastrectomy. On the contrary, in the absence of somatic mutations in liquid biopsies, endoscopic surveillance could continue.

Study Timeline

• Study First Submitted: 2020-01-31
• Study First Submitted QC: 2020-01-31
• Study First Posted: 2020-02-05
• Study Start: 2020-11-26
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-10
• Last Update Posted: 2024-01-11
• Primary Completion: 2024-11-26
• Study Completion: 2024-11-26

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

Case:

• Patient>18 years old
• CDH1 or CTNNA1 germline pathogenic variant.
• No history of diffuse gastric cancer.
• French social security.
• Ability to understand and willingness to sign a written informed consent document.

Volunteers:

• Patients > 18years old
• Patients with no oncological history

Exclusion Criteria

for both arms

• Patients with cancer being treated
• Patients with metastatic cancer
• Medical contraindication to general anesthesia or FOGD (bleeding disorder, pregnant women )
• Patients under guardianship or curator

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Unaffected carriers of constitutional mutations	Liquid biopsies (blood, gastric fluid).	Patients with CDH1 or CTNNA1 germline pathogenic variant. No history of diffuse gastric cancer.
All patients with FOGD	Liquid biopsies (blood, gastric fluid).	without observation of macroscopic lesions paired with cases (age and sex)

Primary Outcome Measures

Name	Time	Method
Number of subjects in whom somatic mutations or methylation profiles are detected.	Over two years of surveillance

Secondary Outcome Measures

Name	Time	Method
Replicability of observations over successive endoscopies. Correlation between blood and gastric fluid.	Over two years of surveillance

Trial Locations

Locations (1)

Hopital Pitié Salpetrière; 🇫🇷 Paris, France