Confocal Endoscopic Microscopy for Detection of Early Stage Gastric Cancer in Subjects With Hereditary Diffuse Gastric Cancer Syndrome

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT03648879
• Collaborator: (none)
• Enrollment: 37
• Location: 1
• Arm: 1
• Actual Duration (Months): 14.8
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

Background:

People with hereditary gastric cancer syndrome are at increased risk of getting cancer in their stomach. These people should have regular endoscopies and biopsies to check for cancer if they are choosing to keep their stomach. Researchers want to see if they can improve the detection of cancer by endoscopy. Improved endoscopies could better detect early signs of cancer in people with this syndrome.

Objective:

To see if a small microscope attached to an endoscope to inspect the stomach lining is better than regular endoscopy to find the first signs of cancer in the stomach.

Eligibility:

People ages 18 and older who have a personal or family history of a hereditary gastric cancer syndrome or have a mutation that is known to lead to gastric cancer

Design:

Participants will be screened over the phone or in person with:

• Personal and family medical history

• Review of their medical records

Participants will have a physical exam. Then they will be put under general anesthesia. They will have an endoscopy. A lighted tube will be inserted into the mouth and go down to the stomach. First, the standard device will be used. Then participants will be injected with fluorescein. This is a contrast agent. Then the microscope will be added to the tube and the endoscopic evaluation of the stomach will be repeated. During the procedure, biopsies will be taken from different areas of the stomach. Participants will be observed for a few hours after the procedure.

About 14 days after the endoscopy, participants will be asked to return to the clinic for a follow-up visit. This visit can also be conducted over the phone.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer; Gastric Neoplasms	Device: Endoscope+Cellvizio(R) 100 microscope	Phase 2

Detailed Description

Background:

Hereditary Diffuse Gastric Cancer (HDGC) syndrome is caused by a germline mutation in the Cadherin 1 (CDH1) gene. Carriers of this mutation have a 56-70% lifetime risk of developing gastric adenocarcinoma. Current international guidelines recommend endoscopic screening of CDH1 mutation carriers that consists of systematic biopsies of an otherwise normal appearing stomach. However, this approach lacks sufficient sensitivity for detecting intramucosal foci of signet ring cells (SRC), which are pathognomonic of HDGC syndrome. The goal of the current study is to utilize confocal endoscopic microscopy (CEM) for screening the gastric mucosa in this high-risk population.

Objective:

Determine if confocal endoscopic microscopy (CEM) will afford greater sensitivity for detection of signet ring cells (SRC) foci in CDH1 germline mutation carriers.

Eligibility:

CDH1 germline mutation carriers, or those who meet clinical criteria for HDGC testing but have tested negative for a CDH1 gene mutation or those who have other germline mutations suspected to be, or reported to be, associated with HDGC (e.g. Catenin Alpha 1 (CTNNA1).

Design:

Phase II, single-institution study of CEM for detection of intramucosal SRC foci compared to current systematic gastric mapping procedure.

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Phase II Study Evaluating Confocal Endoscopic Microscopy for Detection of Early Stage Gastric Cancer in Subjects With Hereditary Diffuse Gastric Cancer Syndrome
• Actual Study Start Date: Feb 11, 2019
• Actual Primary Completion Date: Apr 20, 2020
• Actual Study Completion Date: May 5, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1/Arm 1 - Upper white-light endoscopy and confocal endoscopic microscopy Upper white-light endoscopy and confocal endoscopic microscopy	Device: Endoscope+Cellvizio(R) 100 microscope; Patients will undergo white-light, upper endoscopy. In addition, during this endoscopy patients will undergo Confocal Endoscopic Microscopy (CEM) using the Cellvizio probe (Mauna Kea Technologies) to scan the same anatomic zones.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Detectable Confocal Endoscopic Microscopy (CEM) w/Greater Sensitivity for Detection of Signet Ring Cells (SRC)Foci in Cadherin-1 (CDH1) Germline Mutation Carriers Compared to Current Method of Standard White Light Endoscopy [14 days]

   Sensitivity for detection of SRC foci in CDH1 germline mutation carriers was assessed by confocal endoscopic microscopy (CEM) compared to the current method of and standard white light endoscopy. Sensitivity in CEM and WLE is defined as the percentage of participants with detectable cancer on endoscopic biopsy.

Secondary Outcome Measures

1. Percentage of Participants Who Have Signet Ring Cells (SRC) Foci Not Identified by Confocal Endoscopic Microscopy (CEM) [Date of enrollment to date of prophylactic gastrectomy, approximately 6 months or an average of 1 month up to 12 months.]

   In participants who choose to undergo prophylactic total gastrectomy with permanent pathologic analysis, the false negative rate (the fraction of participants who have SRC foci not identified by CEM and White Light Endoscopy techniques) will be determined and reported. The fraction percentage of patients who underwent prophylactic total gastrectomy with findings of SRC foci in the gastrectomy specimen will represent the denominator (number) and the number of patients with negative findings by CEM and White Light Endoscopy (WLE) will represent the numerator (number) to generate the false negative detection rate (fraction) for CEM and WLE, respectively.

Other Outcome Measures

1. Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) [Date of enrollment to date off study, approximately 11 months and 19 days.]

   Here is the number of participants with serious and 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. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• INCLUSION CRITERIA:

• Patients with Cadherin-1 (CDH1) germline mutation known to be pathogenic or likely pathogenic, which may also be classified as "significant" or "likely significant" (patients with variants of "uncertain significance " are excluded)

or

-Patients with Catenin Alpha 1 (CTNNA1) and partner and localizer of breast cancer 2 (BRCA2) (PALB2) germline mutations suspected to be, or reported to be, associated with hereditary diffuse gastric cancer (HDGC) syndrome.

or

• In the absence of a germline CDH1 mutation, patients must meet clinical criteria for genetic testing due to a history suggestive of Hereditary Diffuse Gastric Cancer (HDGC) syndrome

• Age greater than or equal to 18 years.

• Physiologically able to undergo upper endoscopy.

• Ability to understand and the willingness to sign a written informed consent document.

• Pregnant women are eligible during second trimester of pregnancy if clinically indicated for evaluation of cancer.

EXCLUSION CRITERIA:

• Current use of therapeutic anticoagulation medication

• Known bleeding disorder or thrombocytopenia.

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

• Any clinical contraindication to general anesthesia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Jeremy L Davis, M.D., National Cancer Institute (NCI)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 5, 2019
• Informed Consent Form - Jul 22, 2019

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

None provided.

• Responsible Party: Jeremy Davis, M.D., Principal Investigator, National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT03648879
• Other Study ID Numbers: 180141; 18-C-0141
• First Posted: Aug 28, 2018
• Last Update Posted: Jul 12, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Jeremy Davis, M.D., Principal Investigator, National Cancer Institute (NCI): Diagnostic; Diagnosis; EGD; Examination of Stomach
• Additional relevant MeSH terms: Stomach Neoplasms

Study Results

Participant Flow

Arm/Group Title	1/Arm 1 - Upper White-light Endoscopy and Confocal Endoscopic Microscopy
Arm/Group Description	Upper white-light endoscopy and confocal endoscopic microscopy Endoscope+Cellvizio(R) 100 microscope: Patients will undergo white-light, upper endoscopy. In addition, during this endoscopy patients will undergo Confocal Endoscopic Microscopy (CEM) using the Cellvizio probe (Mauna Kea Technologies) to scan the same anatomic zones.
Period Title: Overall Study
STARTED	37
COMPLETED	36
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	1/Arm 1 - Upper White-light Endoscopy and Confocal Endoscopic Microscopy
Arm/Group Description	Upper white-light endoscopy and confocal endoscopic microscopy Endoscope+Cellvizio(R) 100 microscope: Patients will undergo white-light, upper endoscopy. In addition, during this endoscopy patients will undergo Confocal Endoscopic Microscopy (CEM) using the Cellvizio probe (Mauna Kea Technologies) to scan the same anatomic zones.
Overall Participants	37
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	30 81.1%
>=65 years	7 18.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.51 (14.02)
Sex: Female, Male (Count of Participants)
Female	28 75.7%
Male	9 24.3%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	4 10.8%
Not Hispanic or Latino	31 83.8%
Ethnicity Unknown or Not Reported	2 5.4%
White	33 89.2%
Race Other	2 5.4%
Race Unknown	2 5.4%
Region of Enrollment (participants) [Number]
United States	37 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Detectable Confocal Endoscopic Microscopy (CEM) w/Greater Sensitivity for Detection of Signet Ring Cells (SRC)Foci in Cadherin-1 (CDH1) Germline Mutation Carriers Compared to Current Method of Standard White Light Endoscopy
Description	Sensitivity for detection of SRC foci in CDH1 germline mutation carriers was assessed by confocal endoscopic microscopy (CEM) compared to the current method of and standard white light endoscopy. Sensitivity in CEM and WLE is defined as the percentage of participants with detectable cancer on endoscopic biopsy.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

36/37 were evaluable for this outcome measure. One participant was determined to have Cadherin-1 (CDH1) variant of uncertain significance.

Arm/Group Title	1/Arm 1 - Upper White-light Endoscopy and Confocal Endoscopic Microscopy
Arm/Group Description	Upper white-light endoscopy and confocal endoscopic microscopy Endoscope+Cellvizio(R) 100 microscope: Patients will undergo white-light, upper endoscopy. In addition, during this endoscopy patients will undergo Confocal Endoscopic Microscopy (CEM) using the Cellvizio probe (Mauna Kea Technologies) to scan the same anatomic zones.
Measure Participants	36
CEM	16.7 45.1%
White Light Endoscopy	11.1 30%

2. Secondary Outcome

Title	Percentage of Participants Who Have Signet Ring Cells (SRC) Foci Not Identified by Confocal Endoscopic Microscopy (CEM)
Description	In participants who choose to undergo prophylactic total gastrectomy with permanent pathologic analysis, the false negative rate (the fraction of participants who have SRC foci not identified by CEM and White Light Endoscopy techniques) will be determined and reported. The fraction percentage of patients who underwent prophylactic total gastrectomy with findings of SRC foci in the gastrectomy specimen will represent the denominator (number) and the number of patients with negative findings by CEM and White Light Endoscopy (WLE) will represent the numerator (number) to generate the false negative detection rate (fraction) for CEM and WLE, respectively.
Time Frame	Date of enrollment to date of prophylactic gastrectomy, approximately 6 months or an average of 1 month up to 12 months.

Outcome Measure Data

Analysis Population Description

36/37 were evaluable for this outcome measure. One participant was determined to have Cadherin-1 (CDH1) variant of uncertain significance.

Arm/Group Title	1/Arm 1 - Upper White-light Endoscopy and Confocal Endoscopic Microscopy
Arm/Group Description	Upper white-light endoscopy and confocal endoscopic microscopy Endoscope+Cellvizio(R) 100 microscope: Patients will undergo white-light, upper endoscopy. In addition, during this endoscopy patients will undergo Confocal Endoscopic Microscopy (CEM) using the Cellvizio probe (Mauna Kea Technologies) to scan the same anatomic zones.
Measure Participants	36
CEM	67 181.1%
White Light Endoscopy	87 235.1%

3. Other Pre-specified Outcome

Title	Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Description	Here is the number of participants with serious and 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. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time Frame	Date of enrollment to date off study, approximately 11 months and 19 days.

Outcome Measure Data

Analysis Population Description

36/37 were evaluable for this outcome measure. One participant was determined to have Cadherin-1 (CDH1) variant of uncertain significance.

Arm/Group Title	1/Arm 1 - Upper White-light Endoscopy and Confocal Endoscopic Microscopy
Arm/Group Description	Upper white-light endoscopy and confocal endoscopic microscopy Endoscope+Cellvizio(R) 100 microscope: Patients will undergo white-light, upper endoscopy. In addition, during this endoscopy patients will undergo Confocal Endoscopic Microscopy (CEM) using the Cellvizio probe (Mauna Kea Technologies) to scan the same anatomic zones.
Measure Participants	36
Count of Participants [Participants]	1 2.7%

Adverse Events

Time Frame	Date of enrollment to date off study, approximately 11 months and 19 days.
Adverse Event Reporting Description	36/37 were evaluable for adverse events. One participant was determined to have Cadherin-1 (CDH1) variant of uncertain significance.
Arm/Group Title	1/Arm 1 - Upper White-light Endoscopy and Confocal Endoscopic Microscopy
Arm/Group Description	Upper white-light endoscopy and confocal endoscopic microscopy Endoscope+Cellvizio(R) 100 microscope: Patients will undergo white-light, upper endoscopy. In addition, during this endoscopy patients will undergo Confocal Endoscopic Microscopy (CEM) using the Cellvizio probe (Mauna Kea Technologies) to scan the same anatomic zones.
All Cause Mortality
	1/Arm 1 - Upper White-light Endoscopy and Confocal Endoscopic Microscopy
	Affected / at Risk (%)	# Events
Total	0/36 (0%)
Serious Adverse Events
	1/Arm 1 - Upper White-light Endoscopy and Confocal Endoscopic Microscopy
	Affected / at Risk (%)	# Events
Total	0/36 (0%)
Other (Not Including Serious) Adverse Events
	1/Arm 1 - Upper White-light Endoscopy and Confocal Endoscopic Microscopy
	Affected / at Risk (%)	# Events
Total	1/36 (2.8%)
General disorders
Fever	1/36 (2.8%)	1
Infections and infestations
Urinary Tract Infection	1/36 (2.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.