Volatile Organic Compound Assessment in Pancreatic Ductal Adenocarcinoma (VAPOR)

Volatile Organic Compound Assessment in Pancreatic Ductal Adenocarcinoma (VAPOR 1 / BIORESOURCE)

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.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer; PDAC - Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Diagnostic test: Breath test; Diagnostic test: Collection of matched samples of breath, biofluids and pancreatic tissue

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.

• Study Type: Observational
• Enrollment (Anticipated): 963

Contacts and Locations

• Study Contact: Name: Miss Caoimhe M Walsh, MBBS, MRCS; Phone Number: +44 (0)20 7594 3396; Email: vapor@imperial.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Imperial College Healthcare NHS Trust
    • Contact: VAPOR Trial Manager

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients seen in a hospital (secondary or tertiary level care) setting

Description

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
• Patients with active infection, receiving immunosuppressive medications or antibiotics within the preceding eight weeks
• 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

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
VAPOR 1 - PDAC (pancreatic ductal adenocarcinoma); 257 treatment-naive patients with histologically-confirmed* PDAC will be recruited to provide breath samples. *Patients that are due to undergo surgery for suspected PDAC (without pre-operative histological confirmation) may still be recruited despite the lack of pre-operative histological confirmation, assuming PDAC is subsequently confirmed within the resected specimen.	Diagnostic test: Breath test; Patients must be fasted for a minimum of six hours prior to sample collection. For patients undergoing surgery or a procedure (e.g. endoscopy), breath samples must be obtained pre-operatively / prior to the administration of sedation, anaesthetic or other pharmacological agents.
VAPOR 1 - Control patients with benign pancreatic disorders; 257 patients with new-onset diabetes mellitus or chronic pancreatitis will be recruited to provide breath samples. New-onset diabetes is defined as: HbA1c≥48mmol/mol (6.5%), diagnosed within the preceding 6 months.	Diagnostic test: Breath test; Patients must be fasted for a minimum of six hours prior to sample collection. For patients undergoing surgery or a procedure (e.g. endoscopy), breath samples must be obtained pre-operatively / prior to the administration of sedation, anaesthetic or other pharmacological agents.
VAPOR 1 - Control patients with non-specific GI symptoms and a normal pancreas; 257 patients with non-specific gastrointestinal symptoms but a radiologically-normal pancreas will be recruited to provide breath samples. Imaging to confirm a normal pancreas (CT / MRI / ultrasound) must have occurred within the preceding 12 months.	Diagnostic test: Breath test; Patients must be fasted for a minimum of six hours prior to sample collection. For patients undergoing surgery or a procedure (e.g. endoscopy), breath samples must be obtained pre-operatively / prior to the administration of sedation, anaesthetic or other pharmacological agents.
VAPOR Bioresource - PDAC (pancreatic ductal adenocarcinoma); 96 treatment-naive patients with histologically-confirmed* PDAC will be recruited to provide samples of breath, saliva, blood, urine, pancreatic tissue and duodenal aspirate. *Patients that are due to undergo surgery for suspected PDAC (without pre-operative histological confirmation) may still be recruited despite the lack of pre-operative histological confirmation, assuming PDAC is subsequently confirmed within the resected specimen.	Diagnostic test: Collection of matched samples of breath, biofluids and pancreatic tissue; In accordance with routine clinical practices, patients will be fasted for a minimum of six hours prior to surgery. Exhaled breath, saliva, blood and urine will be collected immediately prior to surgery (before induction of general anaesthesia). Pancreatic tissue samples and duodenal aspirate which will be collected upon resection of the pancreatic specimen.
VAPOR Bioresource - Control patients with benign pancreatic disorders; 96 patients with benign pancreatic disorders (such as intraductal papillary mucinous neoplasms, pancreatic mucinous cystic neoplasms, chronic pancreatitis) will be recruited to provide samples of breath, saliva, blood, urine, pancreatic tissue and duodenal aspirate.	Diagnostic test: Collection of matched samples of breath, biofluids and pancreatic tissue; In accordance with routine clinical practices, patients will be fasted for a minimum of six hours prior to surgery. Exhaled breath, saliva, blood and urine will be collected immediately prior to surgery (before induction of general anaesthesia). Pancreatic tissue samples and duodenal aspirate which will be collected upon resection of the pancreatic specimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of VOCs present in breath of subjects with PDAC and controls	Gas Chromatography-Mass Spectrometry (GC-MS) will be used to identify the levels (measured in parts per billion, ppb) of certain cancer-associated VOCs in breath	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of volatile metabolites present in headspace of the urine of subjects with PDAC and controls	Headspace sampling techniques will be used for headspace collection from urine samples. GC-MS will be used to determine the levels (measured in parts per billion, ppb) of certain cancer-associated VOCs within the headspace of urine.	24 months
Characterisation of bacterial species in saliva samples, pancreatic tissue samples and duodenal aspirate samples of subjects with PDAC compared to controls	Bacterial species present will be identified (measured) using sequencing techniques such as 16s or whole genome sequencing.; Bacteria within the saliva samples will be cultured and species isolated; Bacteria from pancreatic biopsies will be separated from the tissue, and will be cultured to isolate the bacterial species; Bacteria derived from duodenal aspirate will be cultured and species isolated	24 months
Levels of VOCs produced by the bacteria isolated from saliva samples, pancreatic tissue samples and duodenal aspirate samples of subjects with PDAC	The cancer-associated bacterial species isolated and identified as part of Outcome Measure 3 will then be re-cultured within a controlled environment. Headspace and media sampling will be performed to identify and measure the levels of volatile metabolites (measured in parts per billion, ppb) present using GC-MS and LC-MS (Liquid Chromatography-Mass Spectrometry) techniques.	24 months

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: The Leeds Teaching Hospitals NHS Trust; Sheffield Teaching Hospitals NHS Foundation Trust; Royal Free Hospital NHS Foundation Trust; Liverpool University Hospitals NHS Foundation Trust; University Hospital Birmingham NHS Foundation Trust; Manchester University NHS Foundation Trust; University Hospital Southampton NHS Foundation Trust; Newcastle-upon-Tyne Hospitals NHS Trust; Imperial College Healthcare NHS Trust; Royal Surrey County Hospital NHS Foundation Trust; Pancreatic Cancer UK
• Investigators: Principal Investigator: Professor George B Hanna, PhD, FRCS, Imperial College London

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 15, 2022
• Primary Completion (ANTICIPATED): July 1, 2024
• Study Completion (ANTICIPATED): January 1, 2025

Study Registration Dates

• First Submitted: January 23, 2023
• First Submitted That Met QC Criteria: February 3, 2023
• First Posted (ESTIMATE): February 14, 2023

Study Record Updates

• Last Update Posted (ESTIMATE): February 14, 2023
• Last Update Submitted That Met QC Criteria: February 3, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Transcriptomics; Microbiome Analysis; Organoids; Breath analysis; Volatile organic compounds (VOCs); Volatolomics; Metabonomics / Lipidomics; Immune profiling
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma
• Other Study ID Numbers: 22HH7787

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