Volatile Organic Compound Assessment in Pancreatic Ductal Adenocarcinoma

Официальное название

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

Обзор

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.

Подробное описание

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: Up to 813 patients will be recruited for the development of this non-invasive PDAC detection model. This will be comprised of three groups: (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.

Вмешательства

• Диагностический тест 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.
• Диагностический тест 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.

Первичные конечные точки

• Levels of VOCs present in breath of subjects with PDAC and controls [Срок оценки: 24 months]

Вторичные конечные точки (3)

• Levels of volatile metabolites present in headspace of the urine of subjects with PDAC and controls [Срок оценки: 24 months]
• Characterisation of bacterial species in saliva samples, pancreatic tissue samples and duodenal aspirate samples of subjects with PDAC compared to controls [Срок оценки: 24 months]
• Levels of VOCs produced by the bacteria isolated from saliva samples, pancreatic tissue samples and duodenal aspirate samples of subjects with PDAC [Срок оценки: 24 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Великобритания · 1 центр

• Imperial College Healthcare NHS Trust — London

Публикации

• Walsh CM, Murray J, Laponogov I, Parker A, Ellis JK, Converso V, Austin E, Boshier PR, Czajkowski C, Spalding D, Al-Mukhtar A, Frampton AE, Roberts KJ, Pandanaboyana S, Halloran C, Costello E, Kocher H, Mitra V, Hamady Z, Al-Sarireh B, Pathak S, Mitchell WK, Siriwardena AK, Westlake C, Pereira SP, Spiliotis I, Biswas S, Vapor Collaborators, Spanel P, Veselkov K, Sharples LD, Hanna GB; VAPOR Collab PMID 40866056

Идентификаторы

NCT: NCT05727020 · 22HH7787

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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