Clinical trial NCT05412758: Augmented Response of Volatile Biomarkers in Assessment of Oesophagogastric Cancer (AROMA 1 / BIORESOURCE)
Official title: Augmented Response of Volatile Biomarkers in Assessment of Oesophagogastric Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Volatile Organic Compounds
Microbiome
Microbioata
Breath Analysis
Oesophageal Cancer
Gastric Cancer
Volatalomics
Metabonomics/Lipidomics
Microbiome Analysis
Transcriptomics
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Imperial College Healthcare NHS Trust
name: Newcastle-upon-Tyne Hospitals NHS Trust
name: University Hospital Birmingham NHS Foundation Trust
name: University Hospital Southampton NHS Foundation Trust
name: Norfolk and Norwich University Hospitals NHS Foundation Trust
name: Nottingham University Hospitals NHS Trust
name: University Hospital Plymouth NHS Trust
name: Royal Surrey County Hospital NHS Foundation Trust
name: University Hospitals Coventry and Warwickshire NHS Trust
name: Guy's and St Thomas' NHS Foundation Trust
name: Portsmouth Hospitals NHS Trust
name: Barking, Havering and Redbridge University Hospitals NHS Trust
name: Northern Care Alliance NHS Foundation Trust
name: Brighton and Sussex University Hospitals NHS Trust
name: University College London Hospitals
name: Cardiff and Vale University Health Board
name: NHS Lothian
name: NHS Tayside
name: York Teaching Hospitals NHS Foundation Trust
name: The Harley Street Clinic
First posted: 2022-06-09
Enrollment: 648
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: There are two arms to this study; AROMA 1 and BIORESOURCE. It is the AROMA 1 arm of the study that involves an intervention. A total of 648 patients will be recruited for development of an augmented breath test to detect oesophageal and gastric cancer at early stages of disease. Three groups, each containing 216 patients, will be recruited: (i) oesophageal cancer (ii) gastric cancer and (iii) control/normal patients with upper gastrointestinal symptoms. After the first baseline breath sample at 0 minutes is collected, subjects will then be asked to consume a standard nutrient drink. Further breath samples will be collected at 15 minutes after consumption of the drink.
Primary purpose: DIAGNOSTIC

Brief summary: Cancer of the stomach and oesophagus is among the world's top five cancers. Survival rates are very poor as the disease presents late and early symptoms are non-specific. The study team has developed a non-invasive test for cancers of the stomach and oesophagus based on the detection of volatile organic compounds in exhaled breath. These compounds are known to be produced by both cancers as well as cancer associated bacteria within the gut.

The proposed innovation is to improve the accuracy of this test by investigating whether simple metabolic substrates can increase the production of these volatile organic compounds by both the tumour and its associated bacteria.

Detailed description: AROMA 1: A total of 648 patients will be recruited for development of an augmented breath test to detect oesophageal and gastric cancer at early stages of disease. Three groups, each containing 216 patients, will be recruited: (i) oesophageal cancer (ii) gastric cancer and (iii) control/normal patients with upper gastrointestinal symptoms. After a baseline breath sample is collected, subjects will then be asked to consume a standard nutrient drink. Further breath samples will be collected at 0 and 15 minutes after consumption of the drink.

Breath samples will be stored on thermal desportion tubes before being transfered to a central laboratory for analysis. Breath samples will be analysed in accordance with existing quality-controlled processes. A combined approach of chromatographic- and real time- mass spectrometric techniques will be applied for VOC profiling.

BIORESOURCE: Samples from 335 patients will be collected in order to establish a biobank for multi-omic analyses. Three groups, each containing 75 patients, will be recruited: (i) oesophageal adenocarcinoma; (ii) gastric adenocarcinoma and (iii) oesophageal controls - benign conditions/normal gastrointestinal tract with upper gastrointestinal symptoms (iv) gastric controls - benign conditions/normal gastrointestinal tract with upper gastrointestinal symptoms. The following biosamples will be collected: breath, urine, saliva, blood, tissue and gastric contents. Collected samples will be utilised in a wide range of studies to investigate the mechanisms of VOC production in cancer. The following analyses will be performed: volatalomics, metabonomics/lipidomics, microbiome analysis, transcriptomics and cell culture experiments.

Eligibility criteria: AROMA 1 Inclusion Criteria:

1. Aged 18-90years
2. Oesophageal/gastric cancer cohort: participants with biopsy proven adenocarcinoma who are treatment naïve
3. Control cohort: participants with normal or benign upper gastrointestinal disease determined on: • Endoscopy within 1 year • Planned endoscopy

AROMA 1 Exclusion criteria:

Patients with the following characteristics will not be eligible for inclusion in this study:

1. Oesophageal squamous cell carcinoma
2. Previous oesophageal and gastric resection
3. Received neoadjuvant chemotherapy for oesophageal or gastric cancer
4. History of another cancer within three years
5. Any form of oesophageal dysplasia (control cohort only)
6. Previously diagnosed with Barrett's oesophagus (control cohort only)
7. Active infection, on immunosuppressive medications or antibiotic therapy within the last 8 weeks
8. Participants with co-morbidities preventing breath collection
9. 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
10. Unable or unwilling to provide informed written consent
11. Pregnant participants

BIORESOURCE inclusion criteria:

1. Aged 18- 90years
2. Oesophageal/gastric cancer cohort: participants with biopsy proven adenocarcinoma who are treatment naïve
3. Oesophageal/gastric control cohort: participants with normal or benign upper gastrointestinal disease determined on: • Planned endoscopy

BIORESOURCE exclusion criteria:

1. Oesophageal squamous cell carcinoma
2. Previous oesophageal and gastric resection
3. Received neoadjuvant chemotherapy for oesophageal or gastric cancer
4. History of another cancer within five years
5. Any form of oesophageal dysplasia (oesophageal/gastric control cohorts only)
6. Previously diagnosed with Barrett's oesophagus (oesophageal/gastric control cohorts only)
7. Active infection, on immunosuppressive medications or antibiotic therapy within the last 8 weeks
8. Participants with co-morbidities preventing breath collection
9. Unable or unwilling to provide informed written consent
10. Pregnant participants

Primary outcomes:
measure: Efficacy of an oral nutrient drink to stimulate the production of volatile organic compounds detected in the breath.
timeFrame: 18 months
Secondary outcomes:
measure: Volatile metabolites present in breath of subjects with oesophagogastric cancer and controls
timeFrame: 18 months
measure: Volatile metabolites present in headspace of the urine of subjects with oesophagogastric cancer and controls
timeFrame: 18 months
measure: Determination of bacterial species and cancer associated volatile compound production from saliva samples of subjects with oesophagogastric cancer.
timeFrame: 18 months
measure: Determination of bacterial species and cancer associated volatile compound production from tissue samples of subjects with oesophagogastric cancer
timeFrame: 18 months
measure: Determination of bacterial species and cancer associated volatile compound production from gastric contents of subjects with oesophagogastric cancer
timeFrame: 18 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College NHS Foundation Trust
Study officials:
affiliation: Imperial College London
name: George Hanna, PhD, FRCS
role: PRINCIPAL_INVESTIGATOR
References: