A Liquid Biopsy for Pancreatic Cancer Early-detection and Disease Monitoring

Brief summary public domain (ClinicalTrials.gov)

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy characterized by an asymptomatic early phase, late diagnosis, and poor survival, particularly in individuals who develop disease outside the context of early-stage detection. Early detection strategies are currently limited to imaging-based surveillance (MRI and endoscopic ultrasound) in selected high-risk populations, but these approaches are invasive, costly, and suboptimal in sensitivity. The aim of this study is to evaluate circulating cell-free and exosome-bound microRNAs as non-invasive biomarkers of PDAC risk and disease biology

Detailed description public domain (ClinicalTrials.gov)

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy characterized by an asymptomatic early phase, late diagnosis, and poor survival, particularly in individuals who develop disease outside the context of early-stage detection. Early detection strategies are currently limited to imaging-based surveillance (MRI and endoscopic ultrasound) in selected high-risk populations-including individuals with hereditary or familial pancreatic cancer and those with mucinous pancreatic cystic lesions-but these approaches are invasive, costly, and suboptimal in sensitivity. The aim of this study is to evaluate circulating cell-free and exosome-bound microRNAs as non-invasive biomarkers of PDAC risk and disease biology, with the hypothesis that combined microRNA profiling can improve molecular risk stratification and potentially anticipate disease progression compared with standard imaging-based surveillance alone. The study population will include adult men and women (≥18 years) at increased risk for PDAC due to familial or hereditary predisposition or mucinous pancreatic cysts, with generally stable health status and existing clinical follow-up; no vulnerable populations are specifically targeted. No medicinal products or medical devices are administered in this study. The procedure under investigation consists exclusively of laboratory-based measurement of microRNA expression from previously collected plasma samples, using validated exosome isolation and quantification techniques, with no impact on clinical management. Available preliminary and published data demonstrate that combined cell-free and exosomal microRNA signatures can detect early-stage PDAC with high accuracy and show dynamic behavior during disease progression and treatment, supporting their relevance for risk stratification and disease monitoring. Clinical, demographic, and laboratory data will be retrieved.

Intervention public domain (ClinicalTrials.gov)

Diagnostic_Test: PANXEON. A panel of circulating microRNA, whose expression level is tested in cell-free and exosome-derived samples

Arm public domain (ClinicalTrials.gov)

Familial pancreatic cancer (FPC) (): This term refers to individuals who are at a higher risk of developing pancreatic cancer based on their family history. There are two main risk categories: * 2 relatives with pancreatic cancer, who are first-degree relative of each other, and at least one should be a first degree relative of the individual for whom surveillance is being considered * 3 or more relatives with pancreatic cancer, regardless of the degree

Arm public domain (ClinicalTrials.gov)

Hereditary pancreatic cancer (HPC) (): This terms encompasses all individuals who are at an increased risk of developing pancreatic cancer based on the presence of a pathogenic (or likely pathogenic) germline variant. More specifically: * All individuals with a pathogenic (or likely pathogenic) germline variant in Serine/Threonine Kinase 11 (STK11), cyclin-dependent kinase inhibitor 2A (CDKN2A), Ataxia-Telangiectasia Mutated (ATM), and Breast cancer type 2 (BRCA2) genes, regardless of their family history of pancreatic cancer * Individuals who have both (i) a pathogenic (or likely pathogenic) germline variant in Breast cancer type 1 (BRCA1), Partner and Localizer of BRCA2 (PALB2), Mutator L Homolog 1 (MLH1), Mutator S Homolog 2 (MSH2), Mutator S Homolog 6 (MSH6), Postmeiotic Segregation 1 Homolog 2 (PMS2), or Epithelial Cell Adhesion Molecule (EPCAM) genes; and (ii) at least one relative diagnosed with pancreatic cancer

Arm public domain (ClinicalTrials.gov)

Mucinous Pancreatic Neoplasms (MPN) (): This term refers collectively to cystic lesions of the pancreas that confer an increased risk of developing pancreatic cancer. Collectively, this term encompasses both Intraductal Pancreatic Mucinous Neoplasms (IPMN) and Mucinous Cystic Neoplasias (MCNs)

Primary outcome public domain (ClinicalTrials.gov)

Sensitivity. True positive rate: the probability of a positive test result, conditioned on the individual truly being positive Time frame: Through study completion, an average of 1 year.

Secondary outcome public domain (ClinicalTrials.gov)

Specificity. Time frame: Through study completion, an average of 1 year.

Secondary outcome public domain (ClinicalTrials.gov)

Proportion of correct predictions (true positives and true negatives) among the total number of cases (i.e., accuracy). Time frame: Through study completion, an average of 1 year.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: * Adult men or women aged ≥18 years at the time of plasma sample collection. * Classification as at increased risk for pancreatic ductal adenocarcinoma (PDAC) due to familial pancreatic cancer or hereditary pancreatic cancer syndrome * Classification as at increased risk for pancreatic ductal adenocarcinoma (PDAC) due to the presence of one (or more) mucinous pancreatic cystic lesion(s). * Availability of stored plasma samples collected as part of routine clinical care or surveillance and archived in the institutional biobank. * Availability of relevant clinical and demographic data in institutional medical records sufficient to address study objectives. * Prior provision of informed consent for biobanking and research use of biological samples and data Exclusion Criteria: * Absence or insufficient quality/quantity of stored plasma samples for laboratory analysis. * Lack of clinical data required for cohort classification and/or outcome assessment. * History of pancreatic surgery or interventional procedures prior to plasma sample collection. * Concurrent active malignancy at the time of sample collection, other than non-melanoma skin cancer. * Samples collected outside routine clinical care or not compliant with institutional biobanking and data protection policies.

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 600 participants (estimated).