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| ID | Type | Description | Link |
|---|---|---|---|
| 18-C-0141 |
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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:
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1/Arm 1 - Upper white-light endoscopy and confocal endoscopic microscopy | Experimental | Upper white-light endoscopy and confocal endoscopic microscopy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Endoscope+Cellvizio(R) 100 microscope | Device | 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 | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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
EXCLUSION CRITERIA:
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| Name | Affiliation | Role |
|---|---|---|
| Jeremy L Davis, M.D. | National Cancer Institute (NCI) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center | Bethesda | Maryland | 20892 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34012620 | Result | 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 carriers. J Gastrointest Oncol. 2021 Apr;12(2):216-225. doi: 10.21037/jgo-20-430. | |
| 31183189 |
| Label | URL |
|---|---|
| NIH Clinical Center Detailed Web Page | View source |
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We will share the study protocol, statistical analysis plan, and clinical study report.
For 2 years from date of study completion.
Requests must be made by clinical investigators with interest and/or expertise in gastrointestinal cancers or endoscopic surveillance techniques.
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| ID | Title | Description |
|---|---|---|
| FG000 | 1/Arm 1 - Upper White-light Endoscopy and Confocal Endoscopic Microscopy | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 5, 2019 |
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| Date of enrollment to date of prophylactic gastrectomy, approximately 6 months or an average of 1 month up to 12 months. |
| Date of enrollment to date off study, approximately 11 months and 19 days. |
| 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. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 1/Arm 1 - Upper White-light Endoscopy and Confocal Endoscopic Microscopy | 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 36/37 were evaluable for this outcome measure. One participant was determined to have Cadherin-1 (CDH1) variant of uncertain significance. | Posted | Number | Percentage of participants | 14 days |
|
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| 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. | 36/37 were evaluable for this outcome measure. One participant was determined to have Cadherin-1 (CDH1) variant of uncertain significance. | Posted | Number | Percentage of participants | Date of enrollment to date of prophylactic gastrectomy, approximately 6 months or an average of 1 month up to 12 months. |
| |||||||||||||||||||||||||||||||||||
| Other Pre-specified | 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. | 36/37 were evaluable for this outcome measure. One participant was determined to have Cadherin-1 (CDH1) variant of uncertain significance. | Posted | Count of Participants | Participants | Date of enrollment to date off study, approximately 11 months and 19 days. |
|
Date of enrollment to date off study, approximately 11 months and 19 days.
36/37 were evaluable for adverse events. One participant was determined to have Cadherin-1 (CDH1) variant of uncertain significance.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 1/Arm 1 - Upper White-light Endoscopy and Confocal Endoscopic Microscopy | 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. | 0 | 36 | 0 | 36 | 1 | 36 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fever | General disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jeremy L. Davis | National Cancer Institute | 240-760-6229 | jeremy.davis@nih.gov |
| Jan 12, 2021 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 22, 2019 | Jan 12, 2021 | ICF_001.pdf |
| ID | Term |
|---|---|
| D013274 | Stomach Neoplasms |
| D004194 | Disease |
| ID | Term |
|---|---|
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D013272 | Stomach Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| Ethnicity Unknown or Not Reported |
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| White |
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| Race Other |
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| Race Unknown |
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