NCT04535414

Phase II Randomized Trial of Bethesda Protocol Compared to Cambridge Method for Detection of Early Stage Gastric Cancer in CDH1 Mutation Carriers

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 195 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Background: Some people have a mutation in the cadherin-1 gene (CDH1) gene that is known to lead to stomach cancer. They are advised to get regular endoscopies with biopsies even if their stomach appears normal. The endoscopy method currently used is called the 'Cambridge Method.' Researchers want to test a new method called the 'Bethesda Protocol.' Objective: To compare the Cambridge Method and Bethesda Protocol and find out which is more efficient in catching early signs of cancer. Eligibility: Adults age 18 and older who have a mutation in the CDH1 gene. Design: Participants will be screened with a review of their medical history, medical records, and physical status. Participants will be put into group 1 (Bethesda Protocol) or group 2 (Cambridge Method). Participants will have a physical exam. They will have endoscopy. For this, they will be put under general anesthesia. They will wear compression cuffs around their legs to prevent blood clots. A lighted tube will be inserted into their mouth and go down to their stomach. For group 1 participants, 88 pieces of tissue will be taken from 22 areas of their stomach. For group 2 participants, 30 pieces of tissue will be taken from 6 areas of their stomach. Then group 2 will be injected with a contrast dye. A microscope will be inserted, and more samples will be taken. About 14 days later, participants will have a follow-up visit or phone call. They may give stool samples every 3 to 6 months for 12 months for research purposes. Participants may have another endoscopy 6-18 months later.

Detailed description

Background: Hereditary Diffuse Gastric Cancer (HDGC) is most often attributed to inactivating germline mutations in the E-cadherin (CDH1) tumor suppressor gene. Mutation carriers have a 24-70% lifetime risk of developing gastric adenocarcinoma. International consensus guidelines recommend endoscopic screening and surveillance of CDH1 mutation carriers who decline risk-reducing total gastrectomy (TG). However, this approach lacks sufficient sensitivity for detection of occult, intramucosal foci of signet ring cancer cells (SRCC), which are pathognomonic of HDGC. Our team has established a systematic endoscopic screening protocol (Bethesda protocol) that demonstrates a higher rate of SRCC detection compared to historic controls using the currently recommended Cambridge method. Objective: Determine if Bethesda protocol provides improved sensitivity for detection of early-stage gastric cancer in CDH1 germline mutation carriers compared to the Cambridge method. Eligibility: Subjects with pathogenic or likely pathogenic CDH1 germline mutation. Age \>=18 years. Physiologically able to undergo upper endoscopy Design: Phase II randomized study to compare Bethesda protocol and Cambridge method for detection of intramucosal SRCC in asymptomatic CDH1 mutation carriers undergoing endoscopic screening or surveillance.

Conditions

• Gastric Cancer
• Gastric Neoplasms
• Gastric Adenocarcinoma

Interventions

Type	Name	Description
DEVICE	Cellvizio (Registered trademark) Real-Time In Vivo Cellular Imaging Platform with Confocal Miniprobes	Participants of both study arms will undergo confocal endomicroscopy of the gastric mucosa until sufficient data for statistically accurate and reliable application of machine learning (i.e., computer models), currently believed to total the first 50 enrolled participants.
DEVICE	Olympus Graphics Interchange Format (GIF) 190 endoscope	Participants will undergo white light endoscopy. The mucosa of the stomach may be thoroughly washed before examination, as medically indicated, and inspection will include repeated inflation and deflation to check distensibility and any abnormal appearing areas will additionally be biopsied. Nontargeted biopsies will be obtained as indicated per the assigned Arm.
PROCEDURE	Gastric mucosal biopsy	As clinically indicated.

Timeline

• Start date: 2023-06-22
• Primary completion: 2024-09-12
• Completion: 2025-01-10
• First posted: 2020-09-02
• Last updated: 2025-01-17
• Results posted: 2025-01-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated device study