Identification of New Theranostic Biomarkers of Pancreatic Tumor Progression

NCT ID: NCT06574373

Last Updated: 2025-09-03

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 3600 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-05-29
• Study Completion Date: 2026-12-31

Brief 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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Patients with IPMN/pancreatic cancer diagnosis

Patients with indolent IPMN, invasive IPMN, and IPMN associated with pancreatic cancer, depending on their clinical course.

Blood Collection Protocol for Patients with Indolent, Invasive, and Pancreatic Cancer-Associated IPMN Based on Clinical Course and Surgical Intervention

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Diagnosis of indolent IPMN under monitoring;
• Diagnosis of malignant IPMN or resectable pancreatic adenocarcinoma with associated IPMN (previously untreated); Written informed consent; Male and female patients aged 18 years or older;

Exclusion Criteria

-Inability to provide written informed consent or to trace patients for the retrospective study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Azienda Ospedaliera Universitaria Integrata Verona

OTHER

Sponsor Role: collaborator

Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale

NETWORK

Sponsor Role: collaborator

University of Messina

OTHER

Sponsor Role: collaborator

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Carbone Carmine

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Carmine Carbone, PhD

Role: PRINCIPAL_INVESTIGATOR

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Locations

Fondazione Policlinico Gemelli

Roma, , Italy

Site Status: RECRUITING

IRCCS Fondazione Policlinico Universitario A. Gemelli

Rome, , Italy

Site Status: NOT_YET_RECRUITING

Countries

Italy

Central Contacts

Carmine Carbone, PhD

Role: CONTACT

carmine.carbone@policlinicogemelli.it

0630155894

Facility Contacts

Carmine Carbone

Role: primary

carmine.carbone@policlinicogemelli.it

06301551

Carmine Carbone, PhD

Role: primary

carmine.carbone@policlinicogemelli.it

+39 0630155259

Geny Piro, PhD

Role: backup

geny.piro@policlinicogemelli.it

+39 0630155259

References

Agostini A, Piro G, Inzani F, Quero G, Esposito A, Caggiano A, Priori L, Larghi A, Alfieri S, Casolino R, Scaglione G, Tondolo V, Cammarota G, Ianiro G, Corbo V, Biankin AV, Tortora G, Carbone C. Identification of spatially-resolved markers of malignant transformation in Intraductal Papillary Mucinous Neoplasms. Nat Commun. 2024 Mar 29;15(1):2764. doi: 10.1038/s41467-024-46994-2.

Reference Type: RESULT

PMID: 38553466 (View on PubMed)

Tanaka M, Fernandez-Del Castillo C, Kamisawa T, Jang JY, Levy P, Ohtsuka T, Salvia R, Shimizu Y, Tada M, Wolfgang CL. Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology. 2017 Sep-Oct;17(5):738-753. doi: 10.1016/j.pan.2017.07.007. Epub 2017 Jul 13.

Reference Type: RESULT

PMID: 28735806 (View on PubMed)

Levink I, Bruno MJ, Cahen DL. Management of Intraductal Papillary Mucinous Neoplasms: Controversies in Guidelines and Future Perspectives. Curr Treat Options Gastroenterol. 2018 Sep;16(3):316-332. doi: 10.1007/s11938-018-0190-2.

Reference Type: RESULT

PMID: 30196428 (View on PubMed)

Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024 Jan-Feb;74(1):12-49. doi: 10.3322/caac.21820. Epub 2024 Jan 17.

Reference Type: RESULT

PMID: 38230766 (View on PubMed)

Other Identifiers

PNRR-MCNT2-2023-12377229

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ID 6797

Identifier Type: -

Identifier Source: org_study_id