Oesophageal Squamous Cell CarcinomaBRAVENCT07714538
Breath Research Narrow Validation for Gastrointestinal Cancer Detection
An observational study of Oesophageal Squamous Cell Carcinoma and Oesophageal Adenocarcinoma, run by Imperial College London at 6 sites in United Kingdom.
Trial summary
The investigators of this study are developing a simple breath test to help detect gastrointestinal (gut) cancers earlier, including cancers of the oesophagus (food pipe), stomach, pancreas, liver and bowel. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oesophageal Squamous Cell Carcinoma, Oesophageal Adenocarcinoma, Gastric Adenocarcinoma
- Type of treatment
- Pill or oral medicine
- How many people
- 1,000 participants
- Where
- 6 sitesUnited Kingdom
- Study dates
- 26 Jul 2026to 2 Feb 2029
- Phase
- Observational
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
- No healthy volunteers
- Adult, Older adult
Study population: Adult Participants who meet the eligibility criteria and are being referred for further specialised investigations within the NHS.
Who may be able to join
- Adult participants ≥ 18 years old who meet at least one of the following criteria
- Colorectal arm:
- Cancer: Histologically-confirmed CRC*
- Control: Non-specific abdominal symptoms with normal or benign colonoscopy findings
- Pancreatic arm:
- Cancer: Histologically-confirmed PDAC*
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- Control: Non-specific abdominal symptoms with a radiologically-normal pancreas
- Oesophagogastric arm:
- Cancer: Histologically-confirmed OGC*
- Control: Non-specific abdominal symptoms with normal or benign upper gastrointestinal endoscopy findings
- Oesophageal squamous arm:
- Cancer: Histologically-confirmed OSCC*
- Control: Non-specific abdominal symptoms with normal or benign upper gastrointestinal endoscopy findings
- Liver arm:
- Cancer: Histologically- or radiologically-confirmed HCC or CCC*
- Control: Non-specific abdominal symptoms with a radiologically-normal liver
- Patients with suspected cancer (e.g. based on imaging) but who do not have histological confirmation prior to participating in the study may still be recruited and followed up to determine whether or not a diagnosis of cancer was subsequently confirmed.
Who cannot join
- Patients who have already received chemotherapy, radiotherapy or surgery for their cancer
- History of another cancer (other than non-melanoma skin cancers) within three years
- Participants with co-morbidities preventing breath collection
- Unable or unwilling to provide informed consent
- (For Oesophagogastric arm only): Allergies to any of the constituents of the nutrient drink including glucose, glycerol, iron sulphate, Maltodextrin (Corn, Potato), Xanthan Gum, Potassium Chloride, tyrosine, phenylalanine, and glutamic acid
- (For Colorectal arm only): Participants receiving bowel prep in the previous 7 days
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
United Kingdom6 sites, 6 recruiting
- Not yet recruiting
NHS Greater Glasgow and Clyde
Glasgow, G12 0XH
Gary Nicholson, MBBS; FRCS, 0141 201 3000, Gary.Nicholson2@nhs.scot
Gary Nicholson, MBBS; FRCS
- Not yet recruiting
Liverpool University Hospitals NHS Foundation Trust
Liverpool, Merseyside, L7 8XP
Andrew Moore, MBBS; MRCP, 0151 706 2000, andrew.moore@liverpoolft.nhs.uk
Andrew Moore, MBBS; MRCP
- Not yet recruiting
The Clatterbridge Cancer Centre NHS Foundation Trust
Liverpool, L7 8YA
Alia Alchawaf, MBBS; MRCP, 0151 556 5000, aliaalchawaf@nhs.net
Alia Alchawaf, MBBS; MRCP
- Not yet recruiting
Royal Free London NHS Foundation Trust
London, NW3 2QG
Georgia Woodfield, MBBS; MRCP, 020 7472 6446, georgia.woodfield@nhs.net
Georgia Woodfield, MBBS; MRCP
- Recruiting
Imperial College Healthcare NHS Trust
London, W12 0NN
Jessie S McClymont, BSc, +44 7434937543, brave-study@imperial.ac.uk
George Hanna, MBBS; PhD; FRSC
- Not yet recruiting
Maidstone and Tunbridge Wells NHS Trust
Maidstone, Kent, ME16 9QQ
Samantha Forner, MBBS; MRCP, 01622 477714, samantha.forner@nhs.net
Samantha Forner, MBBS; MRSCP
About this study
The investigators of this study are developing a simple breath test to help detect gastrointestinal (gut) cancers earlier, including cancers of the oesophagus (food pipe), stomach, pancreas, liver and bowel. These cancers often cause non-specific symptoms that are similar to benign conditions, making early diagnosis difficult. Delays between the onset of symptoms and referral for a diagnostic test such as an endoscopy or a scan, can allow the cancer to progress.
The breath test detects small molecules called volatile organic compounds (VOCs) that are released in exhaled breath. Some of these VOCs are strongly associated with these cancers and may help identify high-risk patients who require urgent investigation.
Read more
In practice, patients who come to their GP with concerning symptoms will be offered the breath test. If the test is positive, patients can be referred promptly for a diagnostic test, while those with a negative result can be reassured and offered re-testing if symptoms persist. Earlier diagnosis could improve access to curative treatment while reducing unnecessary invasive investigations.
Previous studies have identified a panel of VOCs that appear to distinguish patients with gastrointestinal cancers from those without cancer. This study aims to confirm these findings in a new group of participants to determine whether the same biomarkers can be reliably identified.
Participants will provide a breath sample, usually before a hospital procedure they are already scheduled to undergo, and complete a short questionnaire about their medical history and medications. Some participants will also be asked to drink a nutritional supplement before providing a second breath sample. The results will help determine whether the breath test is reliable enough for further clinical evaluation
Read the detailed description
In the United Kingdom, approximately 75,000 patients are diagnosed with, and 45,000 patients die from, the five major gastrointestinal cancers (oesophageal, gastric, pancreatic, liver and colorectal) each year. Early-stage disease is commonly associated with non-specific symptoms that mimic benign conditions.
Diagnosing cancer at an advanced stage limits curative treatment options. The overall 5-year survival for oesophageal, gastric, pancreatic, liver and colorectal cancer remains poor (15.9%, 20.7%, 9.0%, 12.6% and 50.7% respectively) and is strongly dependent on the stage at diagnosis. Currently, only 14.1%, 19.1%, 14.8%, 13.6% and 37.3% of oesophageal, gastric, pancreatic, liver and colorectal cancers are diagnosed at an early stage.
Earlier detection improves survival and quality of life by increasing access to curative treatment, enabling minimally invasive surgery, shortening hospital stays and facilitating an earlier return to normal activities. Avoiding unnecessary invasive investigations also reduces patient anxiety and the risk of procedure-related complications. Streamlining the diagnostic pathway has the potential to reduce unnecessary investigations and waiting times for endoscopy and cross-sectional imaging.
To address the challenge of earlier detection, the investigators of this study have developed a series of non-invasive breath tests that use volatile organic compound (VOC) analysis to identify symptomatic patients at risk of gastrointestinal cancers. In the future, a GP seeing a patient with symptoms suggestive of gastrointestinal cancer could request a breath test to help guide onward referral for endoscopy or imaging. Such tests could benefit patients with non-specific symptoms who do not currently meet existing referral criteria.
As part of this research programme, the investigators have conducted several clinical studies to identify VOC biomarkers associated with gastrointestinal cancers and develop VOC-based clinical prediction models (CPM) for the following cancers:
- Oesophageal and gastric adenocarcinoma (AROMA1)
- Oesophageal squamous cell carcinoma (ViSON)
- Pancreatic cancer (VAPOR1)
- Liver cancer (VOCAL1)
- Colorectal cancer (COBRA1)
The aim of the BRAVE study is to externally validate these VOC-based clinical prediction models in an enriched population, providing confidence in their diagnostic performance before progressing to the next phase of blinded validation studies.
- Conditions
- Oesophageal Squamous Cell Carcinoma, Oesophageal Adenocarcinoma, Gastric Adenocarcinoma, Pancreatic Ductal Adenocarcinoma (PDAC), Cholangiocarcinoma, Hepatocellular Carcinoma (HCC)
- Keywords
- Early Detection, Volatile Organic Compunds, Oesophageal Cancer, Gastric Cancer, Colorectal Cancer, Liver Cancer, Pancreatic Cancer
- Medical subject headings
- Esophageal Squamous Cell Carcinoma, Adenocarcinoma Of Esophagus, Cholangiocarcinoma, Carcinoma, Hepatocellular, Esophageal Neoplasms, Stomach Neoplasms, Colorectal Neoplasms, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Oesophagogastric Arm | Cases will be patients with histology-confirmed, treatment naïve oesophageal (OAC) or gastric adenocarcinoma (GAC) and controls will be patients who have a normal upper GI tract or benign condition as diagnosed on the reference test (upper GI endoscopy). All eligible patients will be invited to participate. Participants will attend a one off research visit, after having fasted for 6 hours (water permitted) and sign a consent form. They will rinse their mouth with water, provide a baseline breath sample and consume an oral stimulant drink (a nutrient supplement). A further breath sample will be collected after 15 minutes, and an additional environment sample will also be collected. Participants will answer questions about their medical and drug history. | |
| Oesophageal SCC Arm | Cases will be patients with histology-confirmed, treatment naive Oesophageal Squamous Cell Carcinoma (OSCC) and controls will be patients who have a normal upper GI tract or benign condition as diagnosed on the reference test (upper GI endoscopy). All eligible patients will be invited to participate. Participants will attend a one-off research visit, after having fasted for 6 hours (water permitted) and sign a consent form. They will rinse their mouth with water and provide a breath sample. An additional environment sample will also be collected. Participants will answer questions about their medical and drug history. | |
| Pancreatic Arm | Cases will be patients with histology-confirmed, treatment naïve pancreatic ductal adenocarcinoma (PDAC) and controls will be patients with non-specific abdominal symptoms and a radiologically-normal pancreas as diagnosed on the reference test (ultrasound, MRI, CT, PET-CT and endoscopic ultrasound). All eligible patients will be invited to participate. Participants will attend a one-off research visit, after having fasted for 6 hours (water permitted) and sign a consent form. They will rinse their mouth with water and provide a breath sample. An additional environment sample will also be collected. Participants will answer questions about their medical and drug history. | |
| Liver Arm | Cases will be patients with histology-confirmed, treatment naïve hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCC) and controls will be patients with non-specific abdominal symptoms with a radiologically-normal liver as diagnosed on the reference test (ultrasound, MRI, CT and PET-CT). All eligible patients will be invited to participate. Participants will attend a one-off research visit, after having fasted for 6 hours (water permitted) and sign a consent form. They will rinse their mouth with water and provide a breath sample. An additional environment sample will also be collected. Participants will answer questions about their medical and drug history. | |
| Colorectal Arm | Cases will be patients with histology-confirmed, treatment naïve colorectal adenocarcinoma (CRC) and controls will be patients with non-specific abdominal symptoms with a normal lower GI tract or benign condition of the colon as diagnosed on the reference test (colonoscopy). All eligible patients will be invited to participate. Participants will attend a one-off research visit, after having fasted for 6 hours (water permitted) and sign a consent form. They will rinse their mouth with water and provide a breath sample. An additional environment sample will also be collected. Participants will answer questions about their medical and drug history. |
What is being measured
The primary outcome is the main question the study is designed to answer.
To validate and refine a series of breath tests to detect the following conditions: CRC, PDAC, OGC, OSCC, HCC and CCC
Estimation of sensitivity, specificity and numbers of false positives (with 95% confidence intervals) for breath tests to detect CRC, PDAC, OGC, OSCC, HCC and CCC.
Measured: 30 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2026
- Study start26 Jul 2026
- Primary completion2 Feb 2029 (estimated)
- Study completion2 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Oesophageal Squamous Cell CarcinomaStudies 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
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Imperial College Healthcare NHS Trust, Maidstone & Tunbridge Wells NHS Trust, Royal Liverpool University Hospital, The Clatterbridge Cancer Centre NHS Foundation Trust, Hull University Teaching Hospitals NHS Trust, Royal Free London NHS Foundation Trust, NHS Greater Glasgow and Clyde, Chelsea and Westminster NHS Foundation Trust, St George's Healthcare NHS Trust
- Responsible party
- Sponsor
- Investigators
- George Hanna, MBBS; PhD; FRSC, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07714538
- Sponsor's protocol ID
- 200069
- Acronym
- BRAVE
- Status last verified
- Oct 2026
- First submitted
- 15 Jul 2026
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided