The Colorectal Breath Analysis (COBRA) Study (COBRA)

• ClinicalTrials.gov Identifier: NCT03699163
• Recruitment Status: Unknown
• First Posted: October 9, 2018
• Last Update Posted: April 21, 2022
• Sponsor: Imperial College London
• Collaborators: Imperial Health Charity; Rosetrees Trust; National Institute for Health Research, United Kingdom
• Information provided by (Responsible Party): Imperial College London

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Colorectal Cancer; Colorectal Polyps; Colorectal Adenocarcinoma	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 Design

• Study Type: Observational
• Actual Enrollment: 1757 participants
• Observational Model: Case-Control
• Time Perspective: Cross-Sectional
• Official Title: Non-invasive Testing for the Diagnosis and Assessment of Colorectal Disease
• Actual Study Start Date: June 3, 2017
• Estimated Primary Completion Date: April 30, 2022
• Estimated Study Completion Date: April 30, 2022

Groups and Cohorts

Group/Cohort	Intervention/treatment
Endoscopy 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.	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.	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.

Outcome Measures

Primary Outcome Measures :

1. Determine the diagnostic accuracy of the proposed breath test for detection of colorectal cancer and colorectal polyps. [ Time Frame: 4 years ]
   Diagnostic accuracy 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.

Secondary Outcome Measures :

1. Confirmation of diagnostic accuracy of the proposed breath test for early detection of colorectal cancer and for colorectal polyps. [ Time Frame: 2 years ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Criteria

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.

Contacts and Locations

Locations

United Kingdom

Homerton Hospital

London, United Kingdom, E9 6SR

St Mark's Hospital

London, United Kingdom, HA1 3UJ

St George's Hospital

London, United Kingdom, SW17 0RE

Chelsea and Westminster Hospital

London, United Kingdom, SW19 9NH

Royal Marsden Hospital

London, United Kingdom, SW3 6JJ

West Middlesex Hospital

London, United Kingdom, TW7 6AF

St Mary's Hospital

London, United Kingdom, W2 1NY

Charing Cross Hospital

London, United Kingdom, W6 8RF

Sponsors and Collaborators

Imperial College London

Imperial Health Charity

Rosetrees Trust

National Institute for Health Research, United Kingdom

Investigators

• Principal Investigator: George B Hanna, FRCS PhD; Imperial College London

More Information

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT03699163
• Other Study ID Numbers: 17SM3783
• First Posted: October 9, 2018
• Last Update Posted: April 21, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Imperial College London:

Volatile organic compounds; Mass spectrometry; Early detection

Additional relevant MeSH terms:

Adenocarcinoma; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type