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

NCT04535414 | Completed Phase 2 Results FDA Device

• 2 other identifiers: 20015020-C-0150
• Study Type: interventional
• Target: 195
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Gastric Cancer; Gastric Neoplasms; Gastric Adenocarcinoma

Keywords

Diagnostic; Diagnosis; HDGC; SRCC; Confocal Endoscopic Microscopy (CEM)

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With Improved Sensitivity for Detection of Early-stage Gastric Cancer in CDH1 Germline Mutation Carriers Compared to the Cambridge Method

  Among participants who undergo gastrectomy, in each of the two arms, the fraction of participants who had signet ring cell carcinoma (SRCCs) previously identified by endoscopic biopsy out of those who had SRCCs detected on final pathologic analysis of gastrectomy explants will be used to determine the difference between 30% sensitivity in the Cambridge method and 60% sensitivity in the Bethesda protocol of each arm on a Fisher's exact test with a 0.05 two-sided significance level and reported with a 95% confidence interval.

  14 days

Secondary Outcomes (2)

• Proportion of Participants Who Had Signet Ring Cell Carcinoma (SRCC) Identified on Final Pathology But Were Negative for SRCC on Esophagogastroduodenoscopy (EGD)

  14 days

• Difference in Fractions of Participants Crude Cancer Detection Rates Between Endoscopy Using the Bethesda Protocol and the Cambridge Method

  14 days

Other Outcomes (1)

• Number of Participants With Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  From the start of endoscopy through 14 days following study interventions, an average of 2 weeks

Study Arms (2)

1/ Arm 1: Bethesda Protocol (investigational) with Confocal Endomicroscopy

EXPERIMENTAL

Bethesda protocol (investigational) with confocal endomicroscopy in assigned participants

Device: Cellvizio (Registered trademark) Real-Time In Vivo Cellular Imaging Platform with Confocal Miniprobes; Device: Olympus Graphics Interchange Format (GIF) 190 endoscope; Procedure: Gastric mucosal biopsy

2/ Arm 2: Cambridge Method (control) with Confocal Endomicroscopy

ACTIVE COMPARATOR

Cambridge method (control) with confocal endomicroscopy in assigned participants

Device: Cellvizio (Registered trademark) Real-Time In Vivo Cellular Imaging Platform with Confocal Miniprobes; Device: Olympus Graphics Interchange Format (GIF) 190 endoscope; Procedure: Gastric mucosal biopsy

Interventions

Cellvizio (Registered trademark) Real-Time In Vivo Cellular Imaging Platform with Confocal Miniprobes DEVICE

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.

1/ Arm 1: Bethesda Protocol (investigational) with Confocal Endomicroscopy; 2/ Arm 2: Cambridge Method (control) with Confocal Endomicroscopy

Olympus Graphics Interchange Format (GIF) 190 endoscope DEVICE

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.

1/ Arm 1: Bethesda Protocol (investigational) with Confocal Endomicroscopy; 2/ Arm 2: Cambridge Method (control) with Confocal Endomicroscopy

Gastric mucosal biopsy PROCEDURE

As clinically indicated.

1/ Arm 1: Bethesda Protocol (investigational) with Confocal Endomicroscopy; 2/ Arm 2: Cambridge Method (control) with Confocal Endomicroscopy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• An individual who harbors a pathogenic, or likely pathogenic, cadherin-1 gene (CDH1) germline variant.
• Note: individuals with CDH1 variant classified as any of the following are not eligible:
• variant of uncertain significance
• benign
• likely benign.
• Age greater than or equal to 18 years.
• Physiologically able to undergo upper endoscopy.
• Ability of subject to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Any clinical contraindication (e.g., known bleeding disorder, thrombocytopenia) to endoscopic biopsy.
• Unstable angina or recent (within 3 months) myocardial infarction.
• Any clinical contraindication to general anesthesia.
• Re-Enrollment:
• Subject must have previously been enrolled on the study and must have undergone endoscopy. Note: Subject may re-enroll only once after initial endoscopy performed
• Subject must have clinical need for a repeat endoscopy
• Prior on-protocol endoscopy must have occurred at least 6 months (+/- 2 weeks) and no greater than 18 months (+/- 4 weeks)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Stomach Neoplasms; Disease

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Andrew Blakely
• Organization: National Cancer Institute

andrew.blakely@nih.gov

240-760-7647

Study Officials

• Andrew Blakely, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 1, 2020
• First Posted: September 2, 2020
• Study Start: June 22, 2023
• Primary Completion: September 12, 2024
• Study Completion: January 10, 2025
• Last Updated: January 17, 2025
• Results First Posted: January 17, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Bacterial gene sequences data are available once bacterial gene sequences data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Bacterial gene sequences data are made available via GenBank; NCBI places no restrictions on the use or distribution of the GenBank data.

Locations

US (1)