Clinical trial NCT05727020: Volatile Organic Compound Assessment in Pancreatic Ductal Adenocarcinoma
Official title: Volatile Organic Compound Assessment in Pancreatic Ductal Adenocarcinoma (VAPOR 1 / BIORESOURCE)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: PDAC - Pancreatic Ductal Adenocarcinoma
Pancreatic Cancer
Keywords: Volatile organic compounds (VOCs)
Breath analysis
Volatolomics
Metabonomics / Lipidomics
Transcriptomics
Microbiome Analysis
Organoids
Immune profiling
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Pancreatic Cancer UK
name: Imperial College Healthcare NHS Trust
name: Royal Free Hospital NHS Foundation Trust
name: Liverpool University Hospitals NHS Foundation Trust
name: The Leeds Teaching Hospitals NHS Trust
name: Sheffield Teaching Hospitals NHS Foundation Trust
name: University Hospital Southampton NHS Foundation Trust
name: Royal Surrey County Hospital NHS Foundation Trust
name: University Hospital Birmingham NHS Foundation Trust
name: Manchester University NHS Foundation Trust
name: Newcastle-upon-Tyne Hospitals NHS Trust
name: Swansea Bay University Health Board
name: Dorset County Hospital NHS Foundation Trust
name: North Tees and Hartlepool NHS Foundation Trust
name: University Hospital Plymouth NHS Trust
name: Barts & The London NHS Trust
name: Milton Keynes University Hospital NHS Foundation Trust
name: Buckinghamshire Healthcare NHS Trust
name: Southern Health
First posted: 2023-02-14
Enrollment: 963
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients seen in a hospital (secondary or tertiary level care) setting or at an NHS diabetes centre.

Brief summary: Patients with early pancreatic cancer often have symptoms that could also be caused by many common benign conditions, or no symptoms at all. Jaundice, weight loss and pain are 'red flag' symptoms of pancreatic cancer that are linked to incurable disease. At the moment only patients with 'red flag' symptoms are urgently referred for diagnostic testing to find out if they have the cancer. As a result, late diagnosis is a common feature of pancreatic cancer. This leads to limited treatment options being available to patients by the time they are diagnosed, and ultimately results in poor survival rates.

There is a clear need to improve earlier detection of pancreatic cancer so that patients with pancreatic cancer 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 may be altered by pancreatic cancers. For patients with non-specific symptoms, this test would help general practitioners (GPs) to identify those patients that may indeed have an underlying pancreatic cancer, who would benefit from referral for specialised pancreatic cancer tests.

Detailed description: Bioresource study to identify pathways responsible for VOC production: A total of 192 patients will be recruited to provide samples to create a pancreatic biobank. This will be comprised of two groups, each containing 96 patients: (i) patients undergoing resection for pancreatic ductal adenocarcinoma (PDAC); (ii) control patients undergoing pancreatic resection for benign pancreatic disorders (e.g. intraductal papillary mucinous neoplasms, pancreatic mucinous cystic neoplasms, chronic pancreatitis). The following biosamples will be collected from each patient: breath, saliva, blood, urine, pancreatic tissue, duodenal aspirate. Collected samples will be stored in a biobank and will be utilised in a wide range of studies to investigate the mechanisms of VOC production in PDAC. The following analyses will be undertaken: volatolomics, metabonomics / lipidomics, metagenomics / microbiome analysis, transcriptomics, and culture experiments (to establish bacterial, immune and organoid cultures).

VAPOR 1 clinical study: A total of 771 patients will be recruited for the development of this non-invasive PDAC detection model. This will be comprised of three groups, each containing 257 patients: (i) patients with PDAC; (ii) control patients with specified benign pancreatic disorders (new-onset diabetes mellitus, or chronic pancreatitis); (iii) control patients with non-specific gastrointestinal symptoms but a radiologically-normal pancreas. Participants will be required to fast for 6 hours prior to breath sampling. After rinsing their mouth with water, patients will be asked to provide breath samples by exhaling into single-use breath collection bags. Breath will be transferred using a precision pump into thermal desorption (TD) storage tubes. Breath samples will be analysed in accordance with existing quality-controlled processes.

Eligibility criteria: Inclusion Criteria:

* Males and females
* Adult patients ≥ 18 years old
* VAPOR 1: patients with either a) Histologically confirmed PDAC\*; b) New-onset diabetes mellitus or chronic pancreatitis; or c) Non-specific gastrointestinal symptoms, but a radiologically-normal pancreas
* VAPOR Bioresource: patients undergoing pancreatic resection for a) Histologically confirmed PDAC\*; or b) Benign pancreatic disorders e.g. intraductal papillary mucinous neoplasms, pancreatic mucinous cystic neoplasms, chronic pancreatitis

Note: \*Patients undergoing surgery for suspected PDAC (without pre-operative histological confirmation) may be recruited assuming PDAC is confirmed within the resected specimen.

Exclusion Criteria:

* Patients who have already received chemotherapy, radiotherapy or surgery for their PDAC
* History of another cancer within the previous five years
* Previous upper gastrointestinal surgery
* Patients who are unable to provide a breath sample
* Pregnant women
* Patients unable to provide informed written consent
* VAPOR 1: Patients with active infection, receiving immunosuppressive medications or antibiotics within the preceding eight weeks
* VAPOR Bioresource: Patients receiving immunosuppressive medications within the preceding eight weeks

Primary outcomes:
measure: Levels of VOCs present in breath of subjects with PDAC and controls
timeFrame: 24 months
Secondary outcomes:
measure: Levels of volatile metabolites present in headspace of the urine of subjects with PDAC and controls
timeFrame: 24 months
measure: Characterisation of bacterial species in saliva samples, pancreatic tissue samples and duodenal aspirate samples of subjects with PDAC compared to controls
timeFrame: 24 months
measure: Levels of VOCs produced by the bacteria isolated from saliva samples, pancreatic tissue samples and duodenal aspirate samples of subjects with PDAC
timeFrame: 24 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
affiliation: Imperial College London
name: Professor George B Hanna, PhD, FRCS
role: PRINCIPAL_INVESTIGATOR
References: