Clinical trial NCT06121622: Development of New Personalised 3D Preclinical Models of Pancreatic Neuroendocrine Tumours
Official title: Development of New Personalised 3D Preclinical Models of Pancreatic Neuroendocrine Tumours
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Pancreatic Neuroendocrine Tumor
Keywords: PanNET
3D preclinical models
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
First posted: 2023-11-08
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A total number of approximately 70 patients will be enrolled

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Development of New Personalised 3D Preclinical Models of Pancreatic Neuroendocrine Tumours
timeFrame: from the day of surgery until 3 years from surgery
Secondary outcomes:
Other outcomes:
Locations:
city: Milan
country: Italy
facility: IRCCS San Raffele Institute
state: MI
Study officials:
References: