Trial Outcomes & Findings for Phase II Randomized Trial of Bethesda Protocol Compared to Cambridge Method for Detection of Early Stage Gastric Cancer in CDH1 Mutation Carriers (NCT NCT04535414)
NCT ID: NCT04535414
Last Updated: 2025-01-17
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
195 participants
Primary outcome timeframe
14 days
Results posted on
2025-01-17
Participant Flow
Participant milestones
| Measure |
1/ Arm 1: Bethesda Protocol (Investigational) With Confocal Endomicroscopy
Bethesda protocol (investigational) with confocal endomicroscopy in assigned participants
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.
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.
|
2/ Arm 2: Cambridge Method (Control) With Confocal Endomicroscopy
Cambridge method (control) with confocal endomicroscopy in assigned participants
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.
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.
|
|---|---|---|
|
Overall Study
STARTED
|
98
|
97
|
|
Overall Study
COMPLETED
|
89
|
91
|
|
Overall Study
NOT COMPLETED
|
9
|
6
|
Reasons for withdrawal
| Measure |
1/ Arm 1: Bethesda Protocol (Investigational) With Confocal Endomicroscopy
Bethesda protocol (investigational) with confocal endomicroscopy in assigned participants
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.
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.
|
2/ Arm 2: Cambridge Method (Control) With Confocal Endomicroscopy
Cambridge method (control) with confocal endomicroscopy in assigned participants
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.
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.
|
|---|---|---|
|
Overall Study
Taken off study due to principal investigator (PI) discretion.
|
1
|
0
|
|
Overall Study
Cancelled appointment
|
1
|
0
|
|
Overall Study
cancelled - food in stomach
|
2
|
0
|
|
Overall Study
Study closed per PI decision prior to scheduled intervention
|
5
|
5
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Phase II Randomized Trial of Bethesda Protocol Compared to Cambridge Method for Detection of Early Stage Gastric Cancer in CDH1 Mutation Carriers
Baseline characteristics by cohort
| Measure |
1/ Arm 1: Bethesda Protocol (Investigational) With Confocal Endomicroscopy
n=98 Participants
Bethesda protocol (investigational) with confocal endomicroscopy in assigned participants
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.
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.
|
2/ Arm 2: Cambridge Method (Control) With Confocal Endomicroscopy
n=97 Participants
Cambridge method (control) with confocal endomicroscopy in assigned participants
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.
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.
|
Total
n=195 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
85 Participants
n=5 Participants
|
80 Participants
n=7 Participants
|
165 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
13 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Age, Continuous
|
44.46 years
STANDARD_DEVIATION 15.89 • n=5 Participants
|
49.84 years
STANDARD_DEVIATION 13.6 • n=7 Participants
|
47.13 years
STANDARD_DEVIATION 15.04 • n=5 Participants
|
|
Sex: Female, Male
Female
|
56 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
109 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
42 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
86 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
91 Participants
n=5 Participants
|
92 Participants
n=7 Participants
|
183 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity: Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
88 Participants
n=5 Participants
|
90 Participants
n=7 Participants
|
178 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race: Unknown or Not Reported
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
98 participants
n=5 Participants
|
97 participants
n=7 Participants
|
195 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 14 daysPopulation: No participants underwent total gastrectomy in Arm 2.
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.
Outcome measures
| Measure |
1/ Arm 1: Bethesda Protocol (Investigational) With Confocal Endomicroscopy
n=2 Participants
Bethesda protocol (investigational) with confocal endomicroscopy in assigned participants
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.
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.
|
2/ Arm 2: Cambridge Method (Control) With Confocal Endomicroscopy
Cambridge method (control) with confocal endomicroscopy in assigned participants
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.
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.
|
|---|---|---|
|
Proportion of Participants With Improved Sensitivity for Detection of Early-stage Gastric Cancer in CDH1 Germline Mutation Carriers Compared to the Cambridge Method
|
1 proportion of participants
Interval 0.0 to 1.0
|
—
|
SECONDARY outcome
Timeframe: 14 daysPopulation: No participants underwent total gastrectomy in Arm 2.
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.
Outcome measures
| Measure |
1/ Arm 1: Bethesda Protocol (Investigational) With Confocal Endomicroscopy
n=2 Participants
Bethesda protocol (investigational) with confocal endomicroscopy in assigned participants
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.
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.
|
2/ Arm 2: Cambridge Method (Control) With Confocal Endomicroscopy
Cambridge method (control) with confocal endomicroscopy in assigned participants
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.
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.
|
|---|---|---|
|
Proportion of Participants Who Had Signet Ring Cell Carcinoma (SRCC) Identified on Final Pathology But Were Negative for SRCC on Esophagogastroduodenoscopy (EGD)
|
0.5 proportion of participants
Interval 0.0 to 1.0
|
—
|
SECONDARY outcome
Timeframe: 14 daysThe 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.
Outcome measures
| Measure |
1/ Arm 1: Bethesda Protocol (Investigational) With Confocal Endomicroscopy
n=89 Participants
Bethesda protocol (investigational) with confocal endomicroscopy in assigned participants
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.
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.
|
2/ Arm 2: Cambridge Method (Control) With Confocal Endomicroscopy
n=91 Participants
Cambridge method (control) with confocal endomicroscopy in assigned participants
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.
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.
|
|---|---|---|
|
Difference in Fractions of Participants Crude Cancer Detection Rates Between Endoscopy Using the Bethesda Protocol and the Cambridge Method
|
0.31 proportion of participants
Interval 0.24 to 0.46
|
0.20 proportion of participants
Interval 0.13 to 0.31
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From the start of endoscopy through 14 days following study interventions, an average of 2 weeksHere 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.
Outcome measures
| Measure |
1/ Arm 1: Bethesda Protocol (Investigational) With Confocal Endomicroscopy
n=98 Participants
Bethesda protocol (investigational) with confocal endomicroscopy in assigned participants
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.
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.
|
2/ Arm 2: Cambridge Method (Control) With Confocal Endomicroscopy
n=97 Participants
Cambridge method (control) with confocal endomicroscopy in assigned participants
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.
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.
|
|---|---|---|
|
Number of Participants With Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
|
4 Participants
|
0 Participants
|
Adverse Events
1/ Arm 1: Bethesda Protocol (Investigational) With Confocal Endomicroscopy
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
2/ Arm 2: Cambridge Method (Control) With Confocal Endomicroscopy
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
1/ Arm 1: Bethesda Protocol (Investigational) With Confocal Endomicroscopy
n=98 participants at risk
Bethesda protocol (investigational) with confocal endomicroscopy in assigned participants
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.
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.
|
2/ Arm 2: Cambridge Method (Control) With Confocal Endomicroscopy
n=97 participants at risk
Cambridge method (control) with confocal endomicroscopy in assigned participants
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.
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.
|
|---|---|---|
|
General disorders
Fever
|
1.0%
1/98 • Number of events 1 • From the start of endoscopy through 14 days following study interventions, an average of 2 weeks.
|
0.00%
0/97 • From the start of endoscopy through 14 days following study interventions, an average of 2 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection
|
1.0%
1/98 • Number of events 1 • From the start of endoscopy through 14 days following study interventions, an average of 2 weeks.
|
0.00%
0/97 • From the start of endoscopy through 14 days following study interventions, an average of 2 weeks.
|
|
General disorders
Chills
|
1.0%
1/98 • Number of events 1 • From the start of endoscopy through 14 days following study interventions, an average of 2 weeks.
|
0.00%
0/97 • From the start of endoscopy through 14 days following study interventions, an average of 2 weeks.
|
|
Nervous system disorders
Headache
|
1.0%
1/98 • Number of events 1 • From the start of endoscopy through 14 days following study interventions, an average of 2 weeks.
|
0.00%
0/97 • From the start of endoscopy through 14 days following study interventions, an average of 2 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
1.0%
1/98 • Number of events 1 • From the start of endoscopy through 14 days following study interventions, an average of 2 weeks.
|
0.00%
0/97 • From the start of endoscopy through 14 days following study interventions, an average of 2 weeks.
|
|
Gastrointestinal disorders
Dysphagia
|
1.0%
1/98 • Number of events 1 • From the start of endoscopy through 14 days following study interventions, an average of 2 weeks.
|
0.00%
0/97 • From the start of endoscopy through 14 days following study interventions, an average of 2 weeks.
|
|
Gastrointestinal disorders
Abdominal pain
|
1.0%
1/98 • Number of events 1 • From the start of endoscopy through 14 days following study interventions, an average of 2 weeks.
|
0.00%
0/97 • From the start of endoscopy through 14 days following study interventions, an average of 2 weeks.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place