Development of New Personalised 3D Preclinical Models of Pancreatic Neuroendocrine Tumours (3DPanNET)

The goal of this prospective observational study is to generate new personalised 3D preclinical models of pancreatic neuroendocrine tumors. The models will be exploited for studying the mechanisms underlying disease development and progression, as well as for performing drug testing. For the development of the newly proposed models, patients' surgical specimens will be evaluated by the Pathological Unit. If the presence of pathological material in excess, not required for the routine diagnostic procedure, is confirmed, such material will be employed for the generation of the proposed personalised models.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Neuroendocrine Tumor

Detailed Description

Pancreatic neuroendocrine tumors (PanNETs) are characterized by highly heterogeneous biological behavior. Another distinctive feature of these neoplasms is the presence of a dense vascular network, reminiscent of their physiological counterpart. Indeed, the tumor microenvironment plays a critical role in these neoplasms and influence their therapeutic management. Although they are typically indolent in nature, approximately 40% of PanNET patients are metastatic at diagnosis, requiring non-surgical treatments such as somatostatin therapy, chemotherapy, targeted therapy, and peptide receptor radionuclide therapy (PRRT). Furthermore, 1 out of 5 patients experience disease recurrence after surgical resection, necessitating pharmacological therapies. Currently, no specific recommendations exist on the most effective therapeutic sequence to follow in presence of metastatic disease/disease relapse. One of the main reasons behind this unmet clinical need is the scarcity of available preclinical models of these neoplasms able to accurately reproduce the biology and physiology of the primary tumor and that can be used as valid platforms for drug testing.

The study aims to generate a new 3D in vitro model of PanNET, replicating the complex primary tumor in vitro, including also the tumor microenvironment (e.g., vascular network and stroma, essential elements of these neoplasms), personalised for each patient. Indeed, for the development of the newly proposed models, patients' surgical specimens will be initially evaluated by the Pathological Unit and, in the presence of pathological material in excess not required for the routine diagnostic procedure, it will be employed for the generation of the proposed personalised models. 3D culture techniques (e.g., 3D bioprinting) will be used for the development of the models. Moreover, in order to further mimic in vitro the in vivo environment, the models will be maintained under dynamic conditions.

These newly proposed models will be exploited for studying the mechanisms underlying disease development and progression, as well as for performing drug testing.

• Study Type: Observational
• Enrollment (Estimated): 70

Contacts and Locations

• Study Contact: Name: Massimo Falconi, Professor; Phone Number: 0039 022643 6046; Email: falconi.massimo@hsr.it
• Study Contact Backup: Name: Anna Battistella, MD; Phone Number: 0039 02 26433484; Email: battistella.anna1@hsr.it

Study Locations

• Italy
  • MI
    • Milan, MI, Italy, 20132
      • Recruiting
      • IRCCS San Raffele Institute
      • Contact: Stefano Partelli, MD, PhD; Phone Number: 0039 02 2643 7697; Email: partelli.stefano@hsr.it
      • Contact: Cristina Scielzo, PhD; Phone Number: 0039 02 26436487; Email: scielzo.cristina@hsr.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

A total number of approximately 70 patients will be enrolled

Description

Inclusion criteria:

• patients who undergo pancreatic surgical resection for non-functioning pancreatic neuroendocrine tumor
• age ≥ 18 years
• informed consent

Exclusion criteria:

• non-pancreatic neuroendocrine tumor histological diagnosis
• age < 18 years

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of New Personalised 3D Preclinical Models of Pancreatic Neuroendocrine Tumours	Generation of new 3D preclinical models of pancreatic neuroendocrine tumors for the study of the disease biology and for the assessment of drug response	from the day of surgery until 3 years from surgery

Collaborators and Investigators

• Sponsor: IRCCS San Raffaele

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2024
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: October 26, 2023
• First Submitted That Met QC Criteria: November 2, 2023
• First Posted (Actual): November 8, 2023

Study Record Updates

• Last Update Posted (Actual): May 1, 2025
• Last Update Submitted That Met QC Criteria: April 28, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: PanNET; 3D preclinical models
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Glandular and Epithelial; Adenoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Pancreatic Neoplasms; Neuroendocrine Tumors; Adenoma, Islet Cell
• Other Study ID Numbers: 3DPanNET

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No