The Colorectal Breath Analysis (COBRA) Study (COBRA)

Non-invasive Testing for the Diagnosis and Assessment of Colorectal Disease

This study aims to determine whether a breath test could be used for early detection of colorectal cancer and colorectal polyps.

Patients who are attending for a planned colonoscopy or who are scheduled to undergo elective resection of histologically confirmed colorectal cancer (adenocarcinoma) will be approached to provide a breath sample.

Multi platform mass spectrometry analysis will be performed to establish volatile biomarkers that can discriminate between colorectal cancer, benign colorectal disease (e.g. polyps) and healthy controls.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Colorectal Polyps; Colorectal Adenocarcinoma
• Intervention / Treatment: Diagnostic test: Breath sample

Detailed Description

Colorectal cancer is the 2nd most common cause of cancer death in the UK where survival rates are among the lowest in Europe. If diagnosed early survival may exceed 90%.

The proposed breath test is a non-invasive investigation that can detect the presence of volatile organic compounds (VOCs) in breath and their relative abundance in disease states including colorectal cancer. This test has potential to be used in a primary care setting to identify patients at high risk of colorectal cancer, supporting earlier referral for definitive investigation. A negative test may provide reassurance to patients and prevent unnecessary tests in this group. The test could also have an application for colorectal cancer screening.

In this study the investigators will determine the diagnostic accuracy of an exhaled breath test for the detection of colorectal adenocarcinoma and colonic polyps. To determine the accuracy of the breath test a multicentre cross-sectional study will be conducted to analyse single breath samples from patients attending hospital for planned colonoscopy or elective resection of histologically confirmed colorectal cancer. The target for the study is 1463 patients.

Breath collection will be conducted using a previously validated method. Samples of breath (500ml) collected using a CE-marked handheld ReCIVA sampling device (Owlstone Medical Ltd., Cambridge, UK) during a period of tidal breathing (approximately 5minutes) will be absorbed onto thermal desorption tubes (Markes International, Llantrisant, UK). All patients will have received bowel preparation and will be fasted for a minimum of 6 hours prior to the breath sample. Breath samples collected within thermal desorption tubes 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. Quality assurance measures will be formally assessed at each stage of sample handling.

• Study Type: Observational
• Enrollment (Actual): 1855

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital
  • London, United Kingdom, W2 1NY
    • St Mary's Hospital
  • London, United Kingdom, E9 6SR
    • Homerton Hospital
  • London, United Kingdom, HA1 3UJ
    • St Mark's Hospital
  • London, United Kingdom, SW17 0RE
    • St George's Hospital
  • London, United Kingdom, SW19 9NH
    • Chelsea and Westminster Hospital
  • London, United Kingdom, TW7 6AF
    • West Middlesex Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients who are attending for a planned colonoscopy or who are scheduled to undergo elective resection of histologically confirmed colorectal adenocarcinoma will be eligible for inclusion in this study

Description

Inclusion Criteria:

• ≥18 years and ≤90 years of age
• Undergoing planned colonoscopy or elective resection of histologically confirmed colorectal adenocarcinoma
• Fasted >6 hours
• Able to provide informed written consent

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Non cancer control patients; Patients who are attending hospital for a colonoscopy as part of their routine clinical care, or as part of the Bowel Cancer Screening Programme, will be asked to give a sample of their breath prior to the procedure. Those without a finding of colorectal adenocarcinoma will go into this group.	Diagnostic test: Breath sample; Patients will be asked to give a sample of their breath, using the ReCIVA breath testing device. This involves performing tidal breathing whilst wearing a face mask for approximately 5 minutes. Breath (500mls at a flow rate of 200mls/min) is passed over thermal desorption tubes which absorb compounds of interest.
Colorectal cancer patients; Patients who have known pre-diagnosed colorectal cancer (adenocarcinoma) attending hospital as part of their clinical care will be asked to give a breath sample prior to their cancer operation. Patients who are attending hospital for a colonoscopy as part of their routine clinical care, or as part of the Bowel Cancer Screening Programme, will be asked to give a sample of their breath prior to the procedure. Those with a finding of colorectal adenocarcinoma will go into this group.	Diagnostic test: Breath sample; Patients will be asked to give a sample of their breath, using the ReCIVA breath testing device. This involves performing tidal breathing whilst wearing a face mask for approximately 5 minutes. Breath (500mls at a flow rate of 200mls/min) is passed over thermal desorption tubes which absorb compounds of interest.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the Diagnostic Accuracy of the Proposed Breath Test for Detection of Colorectal Cancer in All Patients	Diagnostic accuracy will be measured by calculating the sensitivity and specificity of the test for detection of colorectal cancer, as diagnosed on colonoscopy, using 14 specific VOCs plus BMI as prediction variables.	30 minutes
Determine the Diagnostic Accuracy of Using VOCs Present in Breath for the Detection of Colorectal Cancer in Symptomatic Patients	Diagnostic accuracy will be measured by calculating the sensitivity and specificity of the test for detection of colorectal cancer, as diagnosed on colonoscopy, using 14 specific VOCs plus BMI as prediction variables.	30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmation of diagnostic accuracy of the proposed breath test for early detection of colorectal cancer and for colorectal polyps.	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 colorectal cancer and polyps. 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.	2 years

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: National Institute for Health Research, United Kingdom; Imperial Health Charity; Rosetrees Trust
• Investigators: Principal Investigator: George B Hanna, FRCS PhD, Imperial College London

Publications and helpful links

General Publications

• Woodfield G, Belluomo I, Laponogov I, Veselkov K; COBRA1 WORKING GROUP; Cross AJ, Hanna GB. Diagnostic Performance of a Noninvasive Breath Test for Colorectal Cancer: COBRA1 Study. Gastroenterology. 2022 Nov;163(5):1447-1449.e8. doi: 10.1053/j.gastro.2022.06.084. Epub 2022 Jul 5. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2017
• Primary Completion (Actual): July 1, 2020
• Study Completion (Actual): April 1, 2022

Study Registration Dates

• First Submitted: October 3, 2018
• First Submitted That Met QC Criteria: October 4, 2018
• First Posted (Actual): October 9, 2018

Study Record Updates

• Last Update Posted (Actual): November 21, 2024
• Last Update Submitted That Met QC Criteria: September 24, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Mass spectrometry; Early detection; Volatile organic compounds
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma
• Other Study ID Numbers: 17SM3783

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No