COlorectal BReath Analysis (COBRA2)

The COlorectal BReath Analysis (COBRA2) Study: Non-invasive 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 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.

• Study Type: Observational
• Enrollment (Anticipated): 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 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.

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 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.	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.
CRC group - 250 patients; Patients who are scheduled to undergo elective resection of histologically confirmed colorectal adenocarcinoma.	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.

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 refine 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 (Anticipated): January 1, 2025
• Study Completion (Anticipated): April 1, 2025

Study Registration Dates

• First Submitted: April 25, 2023
• First Submitted That Met QC Criteria: April 25, 2023
• First Posted (Estimate): May 4, 2023

Study Record Updates

• Last Update Posted (Estimate): May 4, 2023
• Last Update Submitted That Met QC Criteria: April 25, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Mass spectrometry; Volatile organic compounds; Breath analysis; Volatolomics
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal 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