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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03648879
Recruitment Status : Completed
First Posted : August 28, 2018
Results First Posted : March 25, 2021
Last Update Posted : July 12, 2021
Sponsor:
Information provided by (Responsible Party):
Jeremy Davis, M.D., National Cancer Institute (NCI)

Study Description
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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
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Study Type : Interventional  (Clinical Trial)
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 : February 11, 2019
Actual Primary Completion Date : April 20, 2020
Actual Study Completion Date : May 5, 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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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
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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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • 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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03648879


Locations
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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Jeremy L Davis, M.D. National Cancer Institute (NCI)
  Study Documents (Full-Text)

Documents provided by Jeremy Davis, M.D., National Cancer Institute (NCI):
Study Protocol and Statistical Analysis Plan  [PDF] June 5, 2019
Informed Consent Form  [PDF] July 22, 2019

More Information
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Additional Information:

Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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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: August 28, 2018    Key Record Dates
Results First Posted: March 25, 2021
Last Update Posted: July 12, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: We will share the study protocol, statistical analysis plan, and clinical study report.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: For 2 years from date of study completion.
Access Criteria: Requests must be made by clinical investigators with interest and/or expertise in gastrointestinal cancers or endoscopic surveillance techniques.

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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., National Cancer Institute (NCI):
Diagnostic
Diagnosis
EGD
Examination of Stomach
Additional relevant MeSH terms:
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Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
 Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases