Identification of New Theranostic Biomarkers of Pancreatic Tumor Progression

NCT06574373 | Recruiting

• 2 other identifiers: ID 6797PNRR-MCNT2-2023-12377229
• Study Type: observational
• Target: 3,600
• Locations: 1 country
• Sites: 2

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.

Conditions

IPMN, Pancreatic

Keywords

IPMN; Pancreatic cancer; precancerous lesions

Outcome Measures

Primary Outcomes (1)

• Association of IPMNs tumorigenic progression with a molecular profile

  Identification of participants with malignant transformation and at least two-fold expression change of a specific molecular profile respect to indolent IPMN. All data will be collected and statistics will be done for the correlation between gene expression markers and malignant transformation.

  2 years

Secondary Outcomes (1)

• Validation of the prognostic molecular profile identified in the primary objective in both archived tissue and plasma samples

  2 years

Study Arms (1)

Patients with IPMN/pancreatic cancer diagnosis

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

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

Interventions

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

Patients with IPMN/pancreatic cancer diagnosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients \>18 years old with Pancreatic IPMN. This cohort will consist of IPMN tissues collected via Formalin-Fixed Paraffin-Embedded from patients who have either developed or have never developed pancreatic cancer associated with IPMN.

You may qualify if:

• 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;

You may not qualify if:

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

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead
• Azienda Ospedaliera Universitaria Integrata Verona: collaborator
• Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale: collaborator
• University of Messina: collaborator

Study Sites (2)

Fondazione Policlinico Gemelli

Roma, 00168, Italy

RECRUITING

IRCCS Fondazione Policlinico Universitario A. Gemelli

Rome, 00168, Italy

NOT YET RECRUITING

Related Publications (4)

• 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.

  PMID: 38553466 RESULT

• 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.

  PMID: 28735806 RESULT

• 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.

  PMID: 30196428 RESULT

• 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.

  PMID: 38230766 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Radiomics imaging

MeSH Terms

Conditions

Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms

Interventions

Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Carmine Carbone, PhD

  Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carmine Carbone, PhD

CONTACT

0630155894; carmine.carbone@policlinicogemelli.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 26, 2024
• First Posted: August 27, 2024
• Study Start: May 29, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)