Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03648879
Other study ID # 180141
Secondary ID 18-C-0141
Status Completed
Phase Phase 2
First received
Last updated
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
Health authority
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

Study Design


Related Conditions & MeSH terms


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.
See also
  Status Clinical Trial Phase
Recruiting NCT05551416 - The EpiGASTRIC/EDGAR Project: New Strategies for the Early Detection and Prevention of Gastric Cancer
Completed NCT05518929 - Hypoxia During Gastroenterological Endoscope Procedures Sedated With Ciprofol In Overweight Or Obesity Patients Phase 4
Recruiting NCT06006390 - CEA Targeting Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of CEA Positive Advanced Solid Tumors Phase 1/Phase 2
Recruiting NCT03219593 - Apatinib as the First-Line Therapy in Elderly Locally Advanced or Metastatic Gastric Cancer Phase 2
Recruiting NCT05489211 - Study of Dato-Dxd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03) Phase 2
Recruiting NCT05536102 - The Effectiveness and Safety of XELOX and Tislelizumab + PLD for Resectable Gastric Cancer (LidingStudy) Phase 2
Active, not recruiting NCT03170960 - Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors Phase 1/Phase 2
Recruiting NCT06010862 - Clinical Study of CEA-targeted CAR-T Therapy for CEA-positive Advanced/Metastatic Malignant Solid Tumors Phase 1
Recruiting NCT05415098 - Study of Safety, Pharmacokinetic and Efficacy of APG-5918 in Advanced Solid Tumors or Lymphomas Phase 1
Active, not recruiting NCT04082364 - Combination Margetuximab, Retifanlimab, Tebotelimab, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ Cancer Phase 2/Phase 3
Withdrawn NCT03766607 - Trastuzumab Beyond Progression in HER2 Positive Metastatic Gastric Cancer Phase 2
Recruiting NCT04118114 - Phase II Study of PRL3-ZUMAB in Advanced Solid Tumors Phase 2
Completed NCT01924533 - Efficacy and Safety Study of Olaparib in Combination With Paclitaxel to Treat Advanced Gastric Cancer. Phase 3
Terminated NCT01641939 - A Study of Trastuzumab Emtansine Versus Taxane in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer Phase 2/Phase 3
Recruiting NCT05107674 - A Study of NX-1607 in Adults With Advanced Malignancies Phase 1
Active, not recruiting NCT04908813 - Study of HLX22 in Combanition With Trastuzumab and Chemotherapy Versus Placebo in Combination With Trastuzumab and Chemotherapy for Treatment of Locally Advanced or Metastatic Gastric Cancer Phase 2
Active, not recruiting NCT04249739 - Pembrolizumab + Capecitabine/Oxaliplatin (CapeOx) -HER2 Nagative and Pembrolizumab + Trastuzumab + Cisplatin/Capecitabine HER2 Positive Phase 2
Recruiting NCT05514158 - To Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Disitamab Vedotin Combined With RC98 in the Treatment of Subjects With HER2-expressing Locally Advanced or Metastatic Gastric Cancer (Including AEG) Phase 1
Recruiting NCT04931654 - A Study to Assess the Safety and Efficacy of AZD7789 in Participants With Advanced or Metastatic Solid Cancer Phase 1/Phase 2
Recruiting NCT03175224 - APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors Phase 2