Colorectal CancerNCT05844514
COlorectal BReath Analysis (COBRA2)
An observational study of Colorectal Cancer, run by Imperial College London at 5 sites in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Breath test
- How many people
- 720 participants
- Where
- 5 sitesUnited Kingdom
- Study dates
- 23 Sep 2022to 1 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients seen in a hospital (secondary or tertiary level care) setting
Who may be able to join
- 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.
Who cannot join
None listed.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United Kingdom5 sites, 3 recruiting
- Recruiting
Chelsea and Westminster Hospital
London
Mr Christos Kontovounisios
- Active, not recruiting
Royal Marsden Hospital
London
- Active, not recruiting
St Mark's Hospital
London
- Recruiting
St Mary's Hospital
London
Professor George B Hanna
- Recruiting
West Middlesex University Hospital
London
Mr Christos Kontovounisios
About this study
Official title: 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.
Read the 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:
- 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.
- Conditions
- Colorectal Cancer
- Being tested
- Breath test
- Keywords
- Volatile organic compounds, Breath analysis, Volatolomics, Mass spectrometry
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Breath testDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: Breath test | |
| 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). Receives: Diagnostic Test: Breath test |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 months
Secondary outcomes (1)
Exploratory comparison between the breath test and FIT.
Assessment of the performance of combining both the breath test and FIT to detect CRC.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2023
- Study start23 Sep 2022
- Primary completion1 Apr 2026 (estimated)
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 720 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, Chelsea and Westminster NHS Foundation Trust, Imperial College Healthcare NHS Trust, Royal Marsden NHS Foundation Trust, London North West Healthcare NHS Trust
- Responsible party
- Sponsor
- Investigators
- Professor George B Hanna, PhD FRCS, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05844514
- Sponsor's protocol ID
- 17SM3783 - SA 04
- Status last verified
- Jun 2025
- First submitted
- 25 Apr 2023
- Last updated
- 13 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fadel MG, Murray J, Woodfield G, Belluomo I, Laponogov I, Parker A, Converso V, Ellis JK, Wheatstone P, Hepburn J, Groves C, Monahan K, Saunders BP, Spanel P, Veselkov K, Cross AJ, Kontovounisios C, Sharples LD, Hanna GB; COBRA2 Collaborators. Non-invasive breath testing to detect colorectal cancer: protocol for a multicentre, case-control development and validation study (COBRA2 study). BMC Cancer. 2025 Jul 29;25(1):1230. doi: 10.1186/s12885-025-14520-2.
PubMed 40731329
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The COlorectal BReath Analysis (COBRA2) Study: Non-invasive Breath Testing to Detect Colorectal Cancer
- ClinicalTrials.gov ID
- NCT05844514
- Acronym / sponsor ID
- 17SM3783 - SA 04
- Conditions
- Colorectal Cancer
- Keywords
- Volatile organic compounds, Breath analysis, Volatolomics, Mass spectrometry
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 720 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, Chelsea and Westminster NHS Foundation Trust, Imperial College Healthcare NHS Trust, Royal Marsden NHS Foundation Trust, London North West Healthcare NHS Trust
- Study start
- 23 Sep 2022 (actual)
- Primary completion
- 1 Apr 2026 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 6 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- 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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group - 470 patients | – | Diagnostic Test: Breath testSymptomatic 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. |
| CRC group - 250 patients | – | Diagnostic Test: Breath testPatients 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients seen in a hospital (secondary or tertiary level care) setting
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Breath testPatients 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. | Diagnostic test | CRC group - 250 patients, Control group - 470 patients |
Primary outcome
Validation and further discovery of VOC biomarkers for CRC.
Time frame: 24 months
GC-MS will be used to confirm the presence of certain CRC-associated VOCs in order to develop the detection model.
1 secondary outcome
Exploratory comparison between the breath test and FIT.
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2025.
- Derived from this study: PubMed 40731329Fadel MG, Murray J, Woodfield G, Belluomo I, Laponogov I, Parker A, Converso V, Ellis JK, Wheatstone P, Hepburn J, Groves C, Monahan K, Saunders BP, Spanel P, Veselkov K, Cross AJ, Kontovounisios C, Sharples LD, Hanna GB; COBRA2 Collaborators. Non-invasive breath testing to detect colorectal cancer: protocol for a multicentre, case-control development and validation study (COBRA2 study). BMC Cancer. 2025 Jul 29;25(1):1230. doi: 10.1186/s12885-025-14520-2.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Professor George B Hanna, PhD FRCS principal investigator
Imperial College London
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Colorectal Cancer, run by Imperial College London at 5 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mr Michael G Fadel, BSc MBBS MRCS (+44 (0)20 7594 3396, m.fadel@imperial.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Validation and further discovery of VOC biomarkers for CRC. (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05844514, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2025.