Volatile Organic Compounds as Breath Biomarkers in Squamous Oesophageal Neoplasms
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18-90
SponsorImperial College London
About this trial
Oesophageal Squamous Cell Carcinoma (OSCC) is a cancer of the food pipe that affects around 2000 patients in the UK every year. It is often detected at an advanced stage, resulting in poor survival (5-year survival less than 20%). Early detection can improve survival (5-year survival \>70%). Therefore, early detection is vital to improving survival.
There are no national screening guidelines, and an endoscopy (A camera test to look at the food pipe) is the only available test to detect OSCC.
Early detection of OSCC is challenging for many reasons. Firstly, early disease symptoms are non-specific, which patients often overlook. Secondly, 'Alarm' symptoms such as weight loss, difficulty swallowing or vomiting blood are signs of advanced stage. Lastly, endoscopy is an invasive test with associated risks and significant discomfort.
The investigators propose to develop a breath test for patients with non-specific symptoms. Breath testing has the ideal characteristics for a triage test because it is non-invasive, simple to perform, cost-effective and highly acceptable to patients. The test is based on identifying volatile organic compounds (VOCs, small molecules) that are produced by the cancer and released in breath.
The breath test will be offered by General Practitioners (GPs) to patients with non-specific symptoms. Those who test positive will be referred for an urgent camera test, and those who test negative can be reassured.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Cancer cohort (n=259): Patients with treatment naïve, histopathology confirmed OSCC.
A normal upper gastrointestinal tract
Benign upper gastrointestinal disease
Disqualifiers
Received some form of treatment (chemotherapy, radiotherapy, immunotherapy, endoscopic resection, or surgery) for OSCC
History of another cancer in the last five years
Non-squamous cell oesophageal cancer
Barrett's oesophagus (with or without dysplasia)
Trial population
Patients with treatment naïve OSCC will be identified via the weekly multidisciplinary team (MDT) meetings (OSCC group). Patients undergoing an OGD for upper GI symptoms will be identified using the National Health Services (NHS) trust booking systems (Control group).
Trial design
Design model
Case-control
Time perspective
Prospective
Treatments tested in this trial
Exhaled breath sampling
Other interventionParticipants will maintain a clear fluid diet for a minimum of 6 hours prior to breath collection. Participants will be asked to provide a breath sample by exhaling into single-use breath collection bags. Using a custom designed gas sampling pump, the breath VOCs will be transferred onto TD tubes at a controlled flow rate. This breath sampling procedure will be repeated once. When the participants' breath sampling is complete, room air (Blank) samples must be taken onto additional TD tubes using the same procedure. The TD tubes will be sealed with long-term storage caps using the CapLok Tool.
Treatment groups
518 Participants
are divided into 2 treatment groupsGroup A: OSCC group1 intervention
Group B: Non-cancer controls1 intervention
Trial outcomes
Primary outcomes
1
To develop a breath test for detection of OSCC
The investigators hypothesise that breath VOCs in OSCC are unique and different to those in non-cancer patients. Replicate breath samples will be analysed by two independent assays using different Thermal Desorption - Gas Chromatography - Time of Flight Mass Spectrometry (TD-GC-TOF-MS) instruments. One assay will use a mid-polar, and the other a polar column stationary phase for optimal determination of VOC chemical classes. The samples will then be recollected and analysed by two-dimensional (2D) TD-GC-TOF-MS for robust VOC identification. Confirming the identity of the top VOCs driving the model will provide chemical validation. Data obtained will be used to refine the model using molecular network analysis. Statistical methods will estimate the probability of OSCC as a function of measured VOCs. Calibrations and method validation will be used to assess and correct for discrimination.
Time frame
36 monthsSecondary outcomes
1
To evaluate the effects of known confounding variables on the target VOCs in OSCC
To develop this clinical triage test, the investigators will use logistic regression modelling. They will assess the linearity of relationships between OSCC risk and continuous variables and explore categorical variables and two-way interactions. Inclusion of patient characteristics (e.g., age, gender, alcohol use and smoking), clinical variables (e.g., symptoms) and VOCs in the model will be determined using a combination of statistical significance (Wald p\<0.05), size of the model coefficients and clinical opinion, drawing on contemporary methods for clinical prediction rules. The investigators will use model reduction techniques such as the LASSO (least absolute shrinkage and selection operator) or Harrell's step-down approach to prevent over-fitting. They will also assess optimism. If there is missing data, the investigators will apply multiple imputation techniques.
Time frame
36 monthsSponsors and contacts
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Imperial College London
Lead sponsor
Imperial College Healthcare NHS Trust
Collaborator
Hull University Teaching Hospitals NHS Trust
Collaborator
Norfolk and Norwich University Hospitals NHS Foundation Trust
Collaborator
University Hospitals Coventry and Warwickshire NHS Trust
Collaborator
Oxford University Hospitals NHS Trust
Collaborator
Velindre NHS Trust
Collaborator
Cardiff and Vale University Health Board
Collaborator
Newcastle-upon-Tyne Hospitals NHS Trust
Collaborator
Liverpool University Hospitals NHS Foundation Trust
Collaborator
Bedfordshire Hospitals NHS Foundation Trust
Collaborator
University Hospitals, Leicester
Collaborator
The Clatterbridge Cancer Centre NHS Foundation Trust
Collaborator
Portsmouth Hospitals NHS Trust
Collaborator
University Hospital Plymouth NHS Trust
Collaborator
NHS Tayside
Collaborator
NHS Highlands
Collaborator
The Christie NHS Foundation Trust
Collaborator
North Cumbria University Hospitals NHS Trust
Collaborator
Maidstone & Tunbridge Wells NHS Trust
Collaborator
University Hospitals of Derby and Burton NHS Foundation Trust
Collaborator
Bradford Teaching Hospitals NHS Foundation Trust
Collaborator
East and North Hertfordshire NHS Trust
Collaborator
Source ClinicalTrials.gov