Non-invasive Testing for Early oEesophageal Cancer and Dysplasia

Recruiting

• Conditions: Barrett Esophagus; Oesophageal Cancer; Barretts Esophagus With Dysplasia
• Interventions: Diagnostic Test: Breath test

• Registration Number: NCT04001478
• Lead Sponsor: Imperial College London

Brief Summary

This study aims to determine whether a breath test could be used for early detection of oesophageal cancer and Barrett's high grade dysplasia.

Patients who are attending for a planned gastroscopy or who are scheduled to undergo elective resection of histologically confirmed early stage oesophageal adenocarcinoma or dysplasia will be approached to provide a breath sample.

Multi platform mass spectrometry analysis will be performed to establish volatile biomarkers that can discriminate between early stage (T1) oesophageal cancer/ Hight grade dysplasia from non cancer healthy controls/non dysplastic Barrett's cancer.

Detailed Description

The incidence of oesophageal adenocarcinoma has been rising over the last decade. Despite improvements in oncological and surgical therapies the associated survival remains poor, mainly due to delays in diagnosis and advanced stage at presentation. Identifying patients at earlier stages as well as those at risk of cancer may lead to survival benefit. Barrett's oesophagus is an established risk factor for the development of oesophageal adenocarcinoma. It has an established histopathologic progression from low-grade, through high-grade dysplasia (HGD) to oesophageal adenocarcinoma (OAC). Barrett's oesophagus patients currently undergo regular endoscopic surveillance to allow earlier detection of oesophageal cancer.

The primary objective is to evaluate the diagnostic accuracy and clinical utility of the volatile organic compounds (VOC) in exhaled breath to detect early stage oesophageal adenocarcinoma and high-grade dysplastic Barrett's oesophagus.

All patients will be fasted for a minimum of 6 hours prior to the breath sample as part of their routine clinical care. Breath collection will be conducted using a previously validated method. Samples of breath (500ml) collected using "breath collecting device utilising bags". Breath samples collected within thermal desorption tubes (Markes International, Llantrisant, UK) will be transferred to a central laboratory for analysis by gas chromatography mass spectrometry (GC-MS) and proton transfer reaction time of flight mass spectrometry (PTR-ToF-MS). Raw data files will be extracted and analysed in accordance with established protocols.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-06-26
• Study First Submitted QC: 2019-06-26
• Study First Posted: 2019-06-28
• Study Start: 2019-10-01
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-24
• Last Update Posted: 2023-07-25
• Primary Completion: 2024-10-31
• Study Completion: 2024-10-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 1000

Inclusion Criteria

• ≥18 years and ≤90 years of age
• Undergoing gastroscopy or elective resection of histologically confirmed oesophageal adenocarcinoma/ high grade dysplasia
• Fasted >6 hours
• Able to provide informed written consent

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Exclusion Criteria

• Any patient <18 years or >90 years of age.
• Lacks capacity or is unable to provide informed written consent.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Early oesophageal cancer (T1)/ Barrett's high grade dysplasia	Breath test	Patients who have known pre-diagnosed T1 oesophageal adenocarcinoma or HGD attending hospital as part of their clinical care will be asked to give a breath sample prior to their endoscopy resection/ cancer operation. Patients will be sampled upon return for follow up endoscopy to assess breath profile changes and correlation with endoscopy findings.
Control group	Breath test	Patients who are attending hospital for a gastroscopy as part of their routine clinical care as a 2 week wait rule referral and those on Barrett's surveillance , will be asked to give a sample of their breath prior to the procedure.
Advanced Oesophageal cancer (T2/3/4)	Breath test	Patients who have been diagnosed with oesophageal adenocarcinoma attending hospital as part of their clinical care will be asked to give a breath sample prior to their endoscopy resection/ cancer operation.

Primary Outcome Measures

Name	Time	Method
Determine the diagnostic accuracy of breath test for detection of early oesophageal cancer and Barrett's high grade dysplasia	4 years	Diagnostic accuracy will be measured by calculating the sensitivity and specificity of the test for detection of early oesophageal cancer/ high grade dysplasia. Sensitivity and specificity values are represented by a number between 0 to 1 indicating the test's ability to pick up true positive results and true negative results respectively, where a number closer to one indicates a greater detection ability.

Secondary Outcome Measures

Name	Time	Method
Diagnostic validation study of the breath profile for prediction of early oeosphageal cancer and high grade dysplasia	3	After diagnostic accuracy has been determined as per objective 1 by the discovery phase of the proposed study, a validation phase will then follow to confirm findings. Diagnostic accuracy of the validation phase results will be measured by calculating the sensitivity and specificity of the test for detection of T1 oesophageal cancer and dysplasia. Sensitivity and specificity values are represented by a number between 0 to 1 indicating the test's ability to pick up true positive results and true negative results respectively, where a number closer to one indicates a greater detection ability.

Trial Locations

Locations (12)

University Hospital Coventry and Warwickshire; 🇬🇧 Coventry, United Kingdom

Newcastle Hospital NHS Foundation Trust; 🇬🇧 Newcastle Upon Tyne, United Kingdom

Imperial College Healthcare Trust; 🇬🇧 London, United Kingdom

University Hospitals Birmingham Nhs Foundation Trust; 🇬🇧 Birmingham, United Kingdom

Royal Liverpool University Hospital; 🇬🇧 Liverpool, United Kingdom

University Hospital Dorset NHS Foundation Trust; 🇬🇧 Bournemouth, United Kingdom

University College London Hospitals Nhs Foundation Trust; 🇬🇧 London, United Kingdom

Nottingham University Hospitals Nhs Trust; 🇬🇧 Nottingham, United Kingdom

University Hospital Southampton NHS Foundation Trust; 🇬🇧 Southampton, United Kingdom

Portsmouth Hospitals Nhs Trust; 🇬🇧 Portsmouth, United Kingdom

Betsi Cadwaladr University Health Board; 🇬🇧 Wrexham, United Kingdom

Guy'S and St Thomas' Nhs Foundation Trust; 🇬🇧 London, United Kingdom