Phase II Randomized Trial of Bethesda Protocol Compared to Cambridge Method for Detection of Early Stage Gastric Cancer in CDH1 Mutation Carriers
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 195
- 试验地点
- 1
- 主要终点
- Proportion of Participants With Improved Sensitivity for Detection of Early-stage Gastric Cancer in CDH1 Germline Mutation Carriers Compared to the Cambridge Method
研究概览
简要总结
Background:
Some people have a mutation in the cadherin-1 gene (CDH1) gene that is known to lead to stomach cancer. They are advised to get regular endoscopies with biopsies even if their stomach appears normal. The endoscopy method currently used is called the 'Cambridge Method.' Researchers want to test a new method called the 'Bethesda Protocol.'
Objective:
To compare the Cambridge Method and Bethesda Protocol and find out which is more efficient in catching early signs of cancer.
Eligibility:
Adults age 18 and older who have a mutation in the CDH1 gene.
Design:
Participants will be screened with a review of their medical history, medical records, and physical status.
Participants will be put into group 1 (Bethesda Protocol) or group 2 (Cambridge Method).
Participants will have a physical exam. They will have endoscopy. For this, they will be put under general anesthesia. They will wear compression cuffs around their legs to prevent blood clots. A lighted tube will be inserted into their mouth and go down to their stomach.
For group 1 participants, 88 pieces of tissue will be taken from 22 areas of their stomach.
For group 2 participants, 30 pieces of tissue will be taken from 6 areas of their stomach. Then group 2 will be injected with a contrast dye. A microscope will be inserted, and more samples will be taken.
About 14 days later, participants will have a follow-up visit or phone call. They may give stool samples every 3 to 6 months for 12 months for research purposes.
Participants may have another endoscopy 6-18 months later.
详细描述
Background:
Hereditary Diffuse Gastric Cancer (HDGC) is most often attributed to inactivating germline mutations in the E-cadherin (CDH1) tumor suppressor gene. Mutation carriers have a 24-70% lifetime risk of developing gastric adenocarcinoma.
International consensus guidelines recommend endoscopic screening and surveillance of CDH1 mutation carriers who decline risk-reducing total gastrectomy (TG). However, this approach lacks sufficient sensitivity for detection of occult, intramucosal foci of signet ring cancer cells (SRCC), which are pathognomonic of HDGC. Our team has established a systematic endoscopic screening protocol (Bethesda protocol) that demonstrates a higher rate of SRCC detection compared to historic controls using the currently recommended Cambridge method.
Objective:
Determine if Bethesda protocol provides improved sensitivity for detection of early-stage gastric cancer in CDH1 germline mutation carriers compared to the Cambridge method.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •An individual who harbors a pathogenic, or likely pathogenic, cadherin-1 gene (CDH1) germline variant.
- •Note: individuals with CDH1 variant classified as any of the following are not eligible:
- •variant of uncertain significance
- •likely benign.
- •Age greater than or equal to 18 years.
- •Physiologically able to undergo upper endoscopy.
- •Ability of subject to understand and the willingness to sign a written informed consent document.
排除标准
- •Any clinical contraindication (e.g., known bleeding disorder, thrombocytopenia) to endoscopic biopsy.
- •Unstable angina or recent (within 3 months) myocardial infarction.
- •Any clinical contraindication to general anesthesia.
- •Re-Enrollment:
- •INCLUSION CRITERIA:
- •Subject must have previously been enrolled on the study and must have undergone endoscopy. Note: Subject may re-enroll only once after initial endoscopy performed
- •Subject must have clinical need for a repeat endoscopy
- •Prior on-protocol endoscopy must have occurred at least 6 months (+/- 2 weeks) and no greater than 18 months (+/- 4 weeks)
研究组 & 干预措施
1/ Arm 1: Bethesda Protocol (investigational) with Confocal Endomicroscopy
Bethesda protocol (investigational) with confocal endomicroscopy in assigned participants
干预措施: Gastric mucosal biopsy (Procedure)
1/ Arm 1: Bethesda Protocol (investigational) with Confocal Endomicroscopy
Bethesda protocol (investigational) with confocal endomicroscopy in assigned participants
干预措施: Cellvizio (Registered trademark) Real-Time In Vivo Cellular Imaging Platform with Confocal Miniprobes (Device)
1/ Arm 1: Bethesda Protocol (investigational) with Confocal Endomicroscopy
Bethesda protocol (investigational) with confocal endomicroscopy in assigned participants
干预措施: Olympus Graphics Interchange Format (GIF) 190 endoscope (Device)
2/ Arm 2: Cambridge Method (control) with Confocal Endomicroscopy
Cambridge method (control) with confocal endomicroscopy in assigned participants
干预措施: Cellvizio (Registered trademark) Real-Time In Vivo Cellular Imaging Platform with Confocal Miniprobes (Device)
2/ Arm 2: Cambridge Method (control) with Confocal Endomicroscopy
Cambridge method (control) with confocal endomicroscopy in assigned participants
干预措施: Olympus Graphics Interchange Format (GIF) 190 endoscope (Device)
2/ Arm 2: Cambridge Method (control) with Confocal Endomicroscopy
Cambridge method (control) with confocal endomicroscopy in assigned participants
干预措施: Gastric mucosal biopsy (Procedure)
结局指标
主要结局
Proportion of Participants With Improved Sensitivity for Detection of Early-stage Gastric Cancer in CDH1 Germline Mutation Carriers Compared to the Cambridge Method
时间窗: 14 days
Among participants who undergo gastrectomy, in each of the two arms, the fraction of participants who had signet ring cell carcinoma (SRCCs) previously identified by endoscopic biopsy out of those who had SRCCs detected on final pathologic analysis of gastrectomy explants will be used to determine the difference between 30% sensitivity in the Cambridge method and 60% sensitivity in the Bethesda protocol of each arm on a Fisher's exact test with a 0.05 two-sided significance level and reported with a 95% confidence interval.
次要结局
- Proportion of Participants Who Had Signet Ring Cell Carcinoma (SRCC) Identified on Final Pathology But Were Negative for SRCC on Esophagogastroduodenoscopy (EGD)(14 days)
- Difference in Fractions of Participants Crude Cancer Detection Rates Between Endoscopy Using the Bethesda Protocol and the Cambridge Method(14 days)
研究者
Andrew Blakely
Principal Investigator
National Cancer Institute (NCI)