COlorectal BReath Analysis (COBRA2)

The COlorectal BReath Analysis (COBRA2) Study: Non-invasive Breath Testing to Detect Colorectal Cancer

Colorectal cancer (CRC) is the second most common cause of cancer death in the United Kingdom, with approximately 17,000 deaths per year. The five-year survival rate from CRC is only 10% when discovered at a late stage, but exceeds 90% if diagnosed early. Symptoms related to CRC can be non-specific, therefore the decision to refer for a colonoscopy can be challenging.

There is a clear need to improve earlier detection of CRC so that patients with CRC can be identified earlier and faster, enabling them to start treatment more quickly.

The study team is developing a non-invasive breath test that detects small molecules called volatile organic compounds (VOCs) that are specific to CRC. For patients with non-specific symptoms, this test would help GPs to identify those patients that may have underlying CRC, who would benefit from referral for specialised CRC tests.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Diagnostic test: Breath test

Detailed Description

The COBRA1 study initially assessed VOCs in CRC and identified a list of 14 VOC biomarkers for CRC and provided a detection model with an area under the receiver operating characteristic curve of 0.91, sensitivity of 83% and specificity of 88% in symptomatic patients.

COBRA2 aims to develop and validate the clinical prediction model (CPM) in the detection of CRC based on the breath test. An exploratory comparison between the breath test and faecal immunochemical test (FIT) will also be carried out to assess whether combining both tests improves diagnostic performance.

Methods: COBRA2 is be a prospective, multicentre validation study. The study team are recruiting the following patients:

The following groups of patients are being recruited:

i) Control group: symptomatic patients who are attending a planned colonoscopy referred under the suspected lower GI cancer pathway. Any patient who is found to have histologically-proven CRC on colonoscopy will be analysed as part of the CRC group.

ii) CRC group: patients who either have a confirmed diagnosis of colorectal adenocarcinoma according to a biopsy, or who are due to undergo surgical resection for suspected CRC (with histological confirmation to follow within three months).

Target recruitment is 720 patients (470 controls, 250 CRC), aiming for 576 patients (376 controls, 200 CRC) with reliable and complete data. Participants are required to maintain a clear fluid diet for a minimum of 4-6 hours prior to sampling and should not have received bowel preparation. Participants will be asked to provide breath samples by exhaling into single-use breath collection bags and breath will be transferred using a precision pump onto thermal desorption (TD) tubes. Breath samples will be analysed with gas chromatography-mass spectrometry in accordance with existing quality control processes.

• Study Type: Observational
• Enrollment (Estimated): 720

Contacts and Locations

• Study Contact: Name: Mr Michael G Fadel, BSc MBBS MRCS; Phone Number: +44 (0)20 7594 3396; Email: m.fadel@imperial.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting
    • West Middlesex University Hospital
    • Contact: Mr Christos Kontovounisios
  • London, United Kingdom
    • Recruiting
    • St Mary's Hospital
    • Contact: Professor George B Hanna
  • London, United Kingdom
    • Recruiting
    • Chelsea and Westminster Hospital
    • Contact: Mr Christos Kontovounisios
  • London, United Kingdom
    • Active, not recruiting
    • Royal Marsden Hospital
  • London, United Kingdom
    • Active, not recruiting
    • St Mark's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients seen in a hospital (secondary or tertiary level care) setting

Description

Inclusion Criteria:

• Patients aged ≥ 18 years referred from primary care with symptoms of suspected CRC.
• Patients with histologically confirmed colorectal adenocarcinoma (stages I-IV) who are treatment naïve (CRC group).

Exclusion Criteria - patients with any of the following will not be eligible for inclusion:

• Previous surgery altering the anatomy of the lower GI tract (e.g., hemicolectomy, anterior resection).
• Previous treatment (neoadjuvant chemotherapy or radiotherapy or immunotherapy) for CRC.
• Received bowel preparation for their colonoscopy procedure.
• History of any other cancer within three years.
• Unable or unwilling to provide informed written consent.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control group - 470 patients; Symptomatic patients who are attending a planned colonoscopy referred under the suspected lower GI cancer pathway. Any patient who is found to have histologically-proven CRC on colonoscopy will be analysed as part of the CRC group.	Diagnostic test: Breath test; Patients must be fasted for a minimum of 4-6 hours prior to breath sample collection. For patients undergoing colonoscopy or surgery, breath samples must be obtained prior to patients receiving bowel preparation in either outpatient clinic or pre-assessment clinic.
CRC group - 250 patients; Patients who either have a confirmed diagnosis of colorectal adenocarcinoma according to a biopsy, or who are due to undergo surgical resection for suspected CRC (with histological confirmation to follow within three months).	Diagnostic test: Breath test; Patients must be fasted for a minimum of 4-6 hours prior to breath sample collection. For patients undergoing colonoscopy or surgery, breath samples must be obtained prior to patients receiving bowel preparation in either outpatient clinic or pre-assessment clinic.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Validation and further discovery of VOC biomarkers for CRC.	GC-MS will be used to confirm the presence of certain CRC-associated VOCs in order to develop the detection model.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory comparison between the breath test and FIT.	Assessment of the performance of combining both the breath test and FIT to detect CRC.	24 months

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Royal Marsden NHS Foundation Trust; Chelsea and Westminster NHS Foundation Trust; National Institute for Health Research, United Kingdom; Imperial College Healthcare NHS Trust; London North West Healthcare NHS Trust
• Investigators: Principal Investigator: Professor George B Hanna, PhD FRCS, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2022
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 25, 2023
• First Submitted That Met QC Criteria: April 25, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Actual): June 13, 2025
• Last Update Submitted That Met QC Criteria: June 10, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Mass spectrometry; Volatile organic compounds; Breath analysis; Volatolomics
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 17SM3783 - SA 04

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