NCT06574373

Identification of New Theranostic Biomarkers of Pancreatic Tumor Progression

New Theranostic Biomarkers of Intraductal Mucinous Neoplasm (IPMN) Progression to Pancreatic Cancer for Patients' Outcome Improvement

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 3,600 (estimated)
• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Intraductal papillary mucinous neoplasms (IPMN) are one of the main precursor lesions of pancreatic ductal adenocarcinoma (PDAC), a lethal disease predicted to become the second leading cause of cancer-related deaths in Western societies within a decade. The mechanisms underlying IPMN progression are poorly understood. The goal of IPMN management is to reduce the risk of patient death due to progression to PDAC through primary and secondary prevention (namely, early diagnosis and risk-reducing surgery). High-risk IPMNs (i.e., high-grade or main duct IPMNs, which account for 57-90% of cases) are referred for surgical resection, while low-risk IPMNs (6-46%) undergo periodic follow-up aimed at monitoring the acquisition of morphological features associated with malignancy over time. However, the clinical management of IPMN remains a significant challenge because the distinction between high and low-risk progression is based on imaging and histological criteria that are not unequivocally recognized and do not take into account the underlying biology of lesions that appear similar but are associated with different clinical behaviors. Consequently, patient risk stratification is often inaccurate, leading to suboptimal treatment. Approximately 1-11% of low-risk IPMN patients assigned to clinical follow-up have developed PDAC. Therefore, it is of paramount importance to improve the understanding of the biology and malignant potential of IPMN to improve prognosis and clinical management of affected patients and guide them toward personalized therapeutic approaches. The availability of markers capable of stratifying IPMN based on their risk of progression to PDAC could enhance the current malignancy criteria assessed in clinical settings by more accurately identifying patients who strongly need surgical resection. \*\*Study Objective\*\* The aim of this study is to identify and validate biomarkers capable of distinguishing between low-risk and high-risk IPMN progression to PDAC. These biomarkers would help more accurately identify IPMN patients who could benefit from therapeutic intervention and/or surgical resection in the future. The study will include patients with IPMN followed at Fondazione Policlinico Gemelli IRCCS Roma, Fondazione G. Pascale IRCCS Naples, Azienda Ospedaliera Universitaria Integrata Verona, and Azienda Ospedaliera Universitaria Integrata Messina.

Detailed description

\*\*AIM1.\*\* 1. \*\*Identification\*\* of genes and biological pathways associated with IPMN malignant transformation. The investigators aim to explore the molecular dynamics of tumor progression, focusing on cellular heterogeneity and phenotypic transitions. 2. \*\*Characterization of the microenvironment\*\* to understand its role in IPMN progression. The investigators will collect archival samples from 240 patients across four centers. 3. \*\*Identification and validation in plasma\*\* of selected patients of differentially expressed markers in indolent IPMN, invasive IPMN, and PDAC. \*\*AIM2.\*\* The investigators will develop knowledge-based tools for diagnosing and treating IPMN and at-risk populations. \*\*AIM3.\*\* The investigators will validate the role of key genes in IPMN carcinogenesis using in vitro study models.

Conditions

• IPMN, Pancreatic

Interventions

Type	Name	Description
OTHER	Blood Collection Protocol for Patients with Indolent, Invasive, and Pancreatic Cancer-Associated IPMN Based on Clinical Course and Surgical Intervention	Blood will be collected from patients with indolent IPMN, invasive IPMN, and IPMN associated with pancreatic cancer, depending on their clinical course. Patients with indolent IPMN will be monitored by the gastroenterology units of their respective institutions, which will inform the patient. Patients with invasive IPMN and/or associated with cancer will undergo surgical resection as part of their standard clinical care, and blood will be collected after informed consent is obtained by the surgical teams at each institution.

Timeline

• Start date: 2025-05-29
• Primary completion: 2026-09-30
• Completion: 2026-12-31
• First posted: 2024-08-27
• Last updated: 2025-09-03

Locations

2 sites across 1 country: Italy