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

Last updated: January 16, 2025
Sponsor: National Cancer Institute (NCI)
Overall Status: Completed

Phase

2

Condition

Stomach Cancer

Gastric Ulcers

Adenocarcinoma

Treatment

Olympus GIF 190 endoscope

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

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

Clinical Study ID

NCT04535414
200150
20-C-0150
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

  • INCLUSION CRITERIA:

  • 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 informedconsent document.

Exclusion

EXCLUSION CRITERIA:

  • Any clinical contraindication (e.g., known bleeding disorder, thrombocytopenia) toendoscopic biopsy.

  • Unstable angina or recent (within 3 months) myocardial infarction.

  • Any clinical contraindication to general anesthesia.

Re-Enrollment:

INCLUSION CRITERIA:

  • Subject must have previously been enrolled on the study and must have undergoneendoscopy. 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) andno greater than 18 months (+/- 4 weeks)

Study Design

Total Participants: 195
Treatment Group(s): 5
Primary Treatment: Olympus GIF 190 endoscope
Phase: 2
Study Start date:
June 22, 2023
Estimated Completion Date:
January 10, 2025

Study 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.

Connect with a study center

  • National Institutes of Health Clinical Center

    Bethesda, Maryland 20892
    United States

    Site Not Available

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