NCT04535414

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

Completed Phase 2 Results posted Last updated 17 January 2025

What this trial tests

Phase 2 trial testing Cellvizio (Registered trademark) Real-Time In Vivo Cellular Imaging Platform with Confocal Miniprobes in Gastric Cancer in 195 participants. Completed in 10 January 2025.

Timeline

22 June 2023

Primary endpoint
12 September 2024

10 January 2025

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	diagnostic
Enrollment	195
Start date	22 June 2023
Primary completion	12 September 2024
Estimated completion	10 January 2025
Sites	1 location across United States

Drugs / interventions tested

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

Conditions studied

• Gastric Cancer — all drugs for Gastric Cancer →
• Gastric Neoplasms — all drugs for Gastric Neoplasms →
• Gastric Adenocarcinoma — all drugs for Gastric Adenocarcinoma →

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Gastric Cancer or Gastric Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Proportion of Participants With Improved Sensitivity for Detection of Early-stage Gastric Cancer in CDH1 Germline Mutation Carriers Compared to the Cambridge Method Primary · 14 days

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.

Group	Value	95% CI
1/ Arm 1: Bethesda Protocol (Investigational) With Confocal Endomicroscopy	1	0 – 1

Proportion of Participants Who Had Signet Ring Cell Carcinoma (SRCC) Identified on Final Pathology But Were Negative for SRCC on Esophagogastroduodenoscopy (EGD) Secondary · 14 days

False negative rate of SRCC detection in participants who undergo risk-reducing total gastrectomy using the Bethesda protocol and Cambridge method. The differences in fractions will be compared using a two-tailed Fisher's exact test and reported with a 95% confidence interval.

Group	Value	95% CI
1/ Arm 1: Bethesda Protocol (Investigational) With Confocal Endomicroscopy	0.5	0 – 1

Difference in Fractions of Participants Crude Cancer Detection Rates Between Endoscopy Using the Bethesda Protocol and the Cambridge Method Secondary · 14 days

The difference in fractions of participants with signet ring cell carcinoma (SRCCs) crude cancer detection rates found on endoscopy by the Bethesda protocol and the Cambridge method determined by the power to detect a difference with a two-sided 0.05 significance level between 15% and 30% crude cancer detection rates and reported with a 95% confidence interval.

Group	Value	95% CI
1/ Arm 1: Bethesda Protocol (Investigational) With Confocal Endomicroscopy	0.31	0.24 – 0.46
2/ Arm 2: Cambridge Method (Control) With Confocal Endomicroscopy	0.20	0.13 – 0.31

Number of Participants With Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) Secondary · From the start of endoscopy through 14 days following study interventions, an average of 2 weeks

Here is the number of participants with non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence.

Group	Value	95% CI
1/ Arm 1: Bethesda Protocol (Investigational) With Confocal Endomicroscopy	4
2/ Arm 2: Cambridge Method (Control) With Confocal Endomicroscopy	0

Adverse events — posted to ClinicalTrials.gov

Time frame: From the start of endoscopy through 14 days following study interventions, an average of 2 weeks.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

1/ Arm 1: Bethesda Protocol (Investigational) With Confocal Endomicroscopy

Serious: 0/98 (0%)

Deaths: 0/98

2/ Arm 2: Cambridge Method (Control) With Confocal Endomicroscopy

Serious: 0/97 (0%)

Deaths: 0/97

Other adverse events (7 terms — click to expand)

Reaction	System	1/ Arm 1: Bethesda Protoco…	2/ Arm 2: Cambridge Method…
Fever	General disorders	—	—
Upper respiratory infection	Respiratory, thoracic and mediastinal disorders	—	—
Chills	General disorders	—	—
Headache	Nervous system disorders	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—
Dysphagia	Gastrointestinal disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—

Data from ClinicalTrials.gov NCT04535414 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Artificial Intelligence in Oncology: A 10-Year ClinicalTrials.gov-Based Analysis Across the Cancer Control Continuum.
   Verma H, Mistry S, Jayam KV, Shrestha P, et al · · 2025 · PMID 41228330 · DOI 10.3390/cancers17213537