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

Gastric Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03648879
• Other study ID #: 180141
• Secondary ID: 18-C-0141
• Status: Completed
• Phase: Phase 2
• Start date: February 11, 2019
• Est. completion date: May 5, 2020

Study information

• Verified date: June 2021
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: May 5, 2020
• Est. primary completion date: April 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

• 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

Related Conditions & MeSH terms

• Gastric Cancer
• Gastric Neoplasms
• Stomach Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Schueler SA, Gamble LA, Curtin BF, Ruff SM, Connolly M, Hannah C, Quezado M, Miettinen M, George M, Blakely AM, Hernandez JM, Heller T, Koh C, Davis JL. Evaluation of confocal laser endomicroscopy for detection of occult gastric carcinoma in CDH1 variant — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	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.	Date of enrollment to date off study, approximately 11 months and 19 days.
Primary	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	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.	14 days
Secondary	Percentage of Participants Who Have Signet Ring Cells (SRC) Foci Not Identified by Confocal Endoscopic Microscopy (CEM)	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.	Date of enrollment to date of prophylactic gastrectomy, approximately 6 months or an average of 1 month up to 12 months.

External Links

•   NIH Clinical Center Detailed Web Page