COlorectal BReath Analysis (COBRA2)

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05844514
• Other study ID #: 17SM3783 - SA 04
• Status: Recruiting
• Start date: September 23, 2022
• Est. completion date: April 1, 2025

Study information

• Verified date: April 2023
• Source: Imperial College London
• Contact: Mr Michael G Fadel, BSc MBBS MRCS
• Phone: +44 (0)20 7594 3396
• Email: m.fadel[@]imperial.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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 therefore has the following aims:

(i) validate VOC biomarkers for CRC identified in COBRA1; (ii) further discovery of VOC biomarkers for CRC using an improved methodology and technology; (iii) refine the detection model with internal validation; (iv) exploratory comparison between a breath test and faecal immunochemical test (FIT); and assessment of the performance of combining both tests to detect CRC.

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

• Control group: symptomatic patients who are attending for a planned colonoscopy referred under the two-week wait pathway. Any patients who is found to have histology proven CRC on colonoscopy will be analysed as part of the CRC group.

• CRC group: patients who are scheduled to undergo elective resection of histologically confirmed colorectal adenocarcinoma.

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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 720
• Est. completion date: April 1, 2025
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Patients aged = 18 years who are seen in secondary or tertiary care with symptoms of suspected CRC referred for a colonoscopy.

• CRC group: patients with histologically confirmed colorectal adenocarcinoma (stages I-IV) who are treatment naïve.

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

• Previous colorectal resection

• Received neoadjuvant chemotherapy/radiotherapy/immunotherapy for CRC

• History of another cancer within five years

• Active infection, on immunosuppressive medication or antibiotic therapy within the last eight weeks

• Unable or unwilling to provide informed written consent.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Diagnostic Test:
• Breath test
Patients must be fasted for a minimum of four 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.

Locations

Country	Name	City	State
United Kingdom	Chelsea and Westminster Hospital	London
United Kingdom	Royal Marsden Hospital	London
United Kingdom	St Mark's Hospital	London
United Kingdom	St Mary's Hospital	London
United Kingdom	West Middlesex University Hospital	London

Sponsors (6)

Lead Sponsor	Collaborator
Imperial College London	Chelsea and Westminster NHS Foundation Trust, Imperial College Healthcare NHS Trust, London North West Healthcare NHS Trust, National Institute for Health Research, United Kingdom, Royal Marsden NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 refine the detection model.	24 months
Secondary	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