Augmented Response of Volatile Biomarkers in Assessment of Oesophagogastric Cancer (AROMA 1 / BIORESOURCE)

Augmented Response of Volatile Biomarkers in Assessment of Oesophagogastric Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Oesophageal Cancer; Microbiome; Volatile Organic Compounds; Transcriptomics; Microbioata; Breath Analysis; Volatalomics; Metabonomics/Lipidomics; Microbiome Analysis
• Intervention / Treatment: Dietary supplement: Oral Stimulant Drink

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 nutirent drink. Further breath samples will be collected at 5, 10 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 225 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.

• Study Type: Interventional
• Enrollment (Estimated): 648
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ayushi Pabari, BSc, MSc; Phone Number: 07986317427; Email: aroma@imperial.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0HS
    • Recruiting
    • Imperial College NHS Foundation Trust
    • Contact: George Hanna, PhD, FRCS; Phone Number: 02033122124; Email: g.hanna@imperial.ac.uk
    • Contact: Piers Boshier, PhD, FRCS; Phone Number: 02033122124; Email: prb03@ic.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 five 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oesophageal/GOJ cancer; AROMA 1: 216 treatment naive patients with oesophageal/GOJ cancer will be recruited to undertake an augmented breath test. BIORESOURCE: 75 treatment naive patients with oesophageal/GOJ cancer will be recruited for biosample collection at the time of their staging laparoscopy procedure.	Dietary supplement: Oral Stimulant Drink; For the AROMA 1 study patients will be requested to consume a nutrient drink (approximately 200 ml) that includes natural ingredients found within a typical human diet. Following consumption of the drink, serial breath tests will be performed to determine varying levels of VOC production in breath; Other Names: Oral Nutrient Drink
Experimental: Gastric cancer; AROMA 1: 216 treatment naive patients with gastric cancer will be recruited to undertake an augmented breath test. BIORESOURCE: 75 treatment naive patients with gastric cancer will be recruited for biosample collection at the time of their staging laparoscopy procedure.	Dietary supplement: Oral Stimulant Drink; For the AROMA 1 study patients will be requested to consume a nutrient drink (approximately 200 ml) that includes natural ingredients found within a typical human diet. Following consumption of the drink, serial breath tests will be performed to determine varying levels of VOC production in breath; Other Names: Oral Nutrient Drink
Experimental: Control/ normal patients with upper gastrointestinal symptoms; AROMA 1: 216 control subjects will be recruited to undertake an augmented breath test. BIORESOURCE: 75 control subjects will be recruited for biosample collection at the time of their routine endoscopy procedure.	Dietary supplement: Oral Stimulant Drink; For the AROMA 1 study patients will be requested to consume a nutrient drink (approximately 200 ml) that includes natural ingredients found within a typical human diet. Following consumption of the drink, serial breath tests will be performed to determine varying levels of VOC production in breath; Other Names: Oral Nutrient Drink

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of an oral nutrient drink to stimulate the production of volatile organic compounds detected in the breath.	Efficacy of the oral stimulant drink will be measured by comparing the relative abundance of certain volatile organic compounds (measured in ppt) detected in the breath. Breath analysis will be performed with the help of Gas Chromatography- Mass Spectrometry (GC-MS)	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Volatile metabolites present in breath of subjects with oesophagogastric cancer and controls	GC-MS will be used to determine the presence of certain cancer associated volatile organic compounds in breath	18 months
Volatile metabolites present in headspace of the urine of subjects with oesophagogastric cancer and controls	Headspace sampling techniques will be used for headspace collection from urine samples. GC-MS will be used to determine the presence of certain cancer associated volatile organic compounds within the headspace of urine.	18 months
Determination of bacterial species and cancer associated volatile compound production from saliva samples of subjects with oesophagogastric cancer.	Bacterial species will be determined using sequencing techniques such as 16s or whole genome sequencing. Bacteria within the saliva samples will be cultured and species isolated. Once isolated, cancer associated species will be re-cultured within a controlled environment. Headspace and media sampling will be performed to determine the volatile metabolites present using GC-MS and LC-MS techniques	18 months
Determination of bacterial species and cancer associated volatile compound production from tissue samples of subjects with oesophagogastric cancer	Bacterial species will be determined using sequencing techniques such as 16s or whole genome sequencing. Tissue and bacteria from biopsies will be separated. Bacteria derived from tissue samples will be cultured and species isolated. Once isolated, cancer associated species will be re-cultured within a controlled environment. Headspace and media sampling will be performed to determine the volatile metabolites present using GC-MS and LC-MS techniques	18 months
Determination of bacterial species and cancer associated volatile compound production from gastric contents of subjects with oesophagogastric cancer	Bacterial species will be determined using sequencing techniques such as 16s or whole genome sequencing. Bacteria from gastric content samples will be separated. Bacteria derived from gastric juices will be cultured and species isolated. Once isolated, cancer associated species will be re-cultured within a controlled environment. Headspace and media sampling will be performed to determine the volatile metabolites present using GC-MS and LC-MS techniques	18 months

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: University College London Hospitals; Northern Care Alliance NHS Foundation Trust; Norfolk and Norwich University Hospitals NHS Foundation Trust; Nottingham University Hospitals NHS Trust; Guy's and St Thomas' NHS Foundation Trust; Barking, Havering and Redbridge University Hospitals NHS Trust; University Hospital Birmingham NHS Foundation Trust; NHS Lothian; University Hospital Southampton NHS Foundation Trust; Brighton and Sussex University Hospitals NHS Trust; Cardiff and Vale University Health Board; NHS Tayside; Newcastle-upon-Tyne Hospitals NHS Trust; Portsmouth Hospitals NHS Trust; Imperial College Healthcare NHS Trust; University Hospital Plymouth NHS Trust; University Hospitals Coventry and Warwickshire NHS Trust; Royal Surrey County Hospital NHS Foundation Trust; York Teaching Hospitals NHS Foundation Trust; The Harley Street Clinic
• Investigators: Principal Investigator: George Hanna, PhD, FRCS, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2022
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: April 1, 2022
• First Submitted That Met QC Criteria: June 7, 2022
• First Posted (Actual): June 9, 2022

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Stimulants
• Other Study ID Numbers: 21HH7100

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