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

• ClinicalTrials.gov Identifier: NCT03648879
• Recruitment Status: Completed
• First Posted: August 28, 2018
• Last Update Posted: September 3, 2020
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Tracking Information

• First Submitted Date: August 24, 2018
• First Posted Date: August 28, 2018
• Last Update Posted Date: September 3, 2020
• Actual Study Start Date: February 11, 2019
• Actual Primary Completion Date: April 20, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 24, 2018)

Determine if confocal endoscopic microscopy (CEM) affords greater sensitivity for detection of SRC foci in CDH1 germline mutation carriers compared to the current method of standard white light endoscopy [ Time Frame: 14 days ]

Determine if confocal endoscopic microscopy (CEM) affords greater sensitivity for detection of SRC foci in CDH1 germline mutation carriers compared to the current method of standard white light endoscopy

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 2, 2020)

Define the false negative rate of CEM detection of SRC foci in those patients who choose to undergo prophylactic total gastrectomy with permanent pathologic analysis [ Time Frame: 14 days ]

In patients who choose to undergo prophylactic total gastrectomy with permanent pathologic analysis, the false negative rate (the fraction of patients who have SRC foci not identified by CEM) will be determined and reported

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Confocal Endoscopic Microscopy for Detection of Early Stage Gastric Cancer in Subjects With Hereditary Diffuse Gastric Cancer Syndrome
• Official Title: Phase II Study Evaluating Confocal Endoscopic Microscopy for Detection of Early Stage Gastric Cancer in Subjects With Hereditary Diffuse Gastric Cancer Syndrome

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.

Detailed Description

Background:

Hereditary Diffuse Gastric Cancer (HDGC) syndrome is caused by a germline mutation in the 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 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. CTNNA1).

Design:

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

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic

Condition

• Gastric Cancer
• Gastric Neoplasms

Intervention

Device: Endoscope+Cellvizio(R) 100 microscope

Patients will undergo white-light, upper endoscopy. In addition, during this endoscopy patients will undergo CEM using the Cellvizio probe (Mauna Kea Technologies) to scan the same anatomic zones.

Study Arms

Experimental: 1/Arm 1

Upper white-light endoscopy and confocal endoscopic microscopy

Intervention: Device: Endoscope+Cellvizio(R) 100 microscope

• Publications *: Ruff S, Curtin B, Quezado M, Heller T, Koh C, Steinberg SM, Connolly M, Hernandez JM, Davis JL. Evaluation of confocal endoscopic microscopy for detection of early-stage gastric cancer in hereditary diffuse gastric cancer (HDGC) syndrome. J Gastrointest Oncol. 2019 Jun;10(3):407-411. doi: 10.21037/jgo.2019.01.04.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 9, 2020): 37
• Original Estimated Enrollment (submitted: August 24, 2018): 27
• Actual Study Completion Date: May 5, 2020
• Actual Primary Completion Date: April 20, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

• INCLUSION CRITERIA:
• Patients with 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 CTNNA1 and PALB2 germline mutations suspected to be, or reported to be, associated with HDGC

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03648879
• Other Study ID Numbers: 180141; 18-C-0141
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
• Study Sponsor: National Cancer Institute (NCI)
• Collaborators: Not Provided

Investigators

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

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: July 30, 2020