Grafts of GSCs Into Brain Organoids for Testing Anti-invasion Drugs (2253)

Grafts of Patient-derived Glioblastoma Stem Cells Onto Autologous Brain Organoids. A Precision Medicine Model for Testing Drugs Against Tumor Invasion

In patients operated for glioblastoma, glioma stem-like cell lines will be obtained from tumor tissue, and IPSCs from skin fibroblasts or PBMCs. Brain organoids will be generated from IPSCs and co-cultured with IPSCs to study brain invasion and ciliogenesis. 3D genome architecture of glioma stem-like cells will be investigated. Gene modulation and pharmacologic strategies to inhibit invasion and restore ciliogenesis will be explored.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma; Glioma, Malignant
• Intervention / Treatment: Other: Biological sample collection

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Roberto Pallini, MD, PhD; Phone Number: +39 06 3015 5414; Email: roberto.pallini@unicatt.it
• Study Contact Backup: Name: Lucia Ricci-Vitiani, PhD; Phone Number: +39 06 49901; Email: lucia.riccivitiani@iss.it

Study Locations

• Italy
  • Rome, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Universitario A. Gemelli IRCCS
    • Contact: Q. Giorgio D'Alessandris, MD; Phone Number: +39 06 3015 5414; Email: quintinogiorgio.dalessandris@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

o be enrolled in the study patients must:

1. Have a radiological diagnosis of supratentorial glioblastoma, or
2. Have a radiological diagnosis of first recurrence of a primary supratentorial glioblastoma (for which a formal histopathologic diagnosis of glioblastoma had made at first surgery), according with RANO criteria (Wen, 2010);
3. Be a candidate to neurosurgery for glioblastoma;
4. Be of an age of 18 years or above;
5. Provide written informed consent for participation to the study.

Exclusion criteria

To be enrolled in the study patients must not:

1. Have not enough pathological material removed at surgery available both for mandatory routine histopathological diagnosis and for the present study, as judged by the Principal Investigator;
2. Have not a definitive pathological diagnosis of a primary supratentorial glioblastoma, according with 2016 WHO classification.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Biological sample collection; Tumor tissue for glioma stem-like cell culture generation. Skin or PBMC for organoid generation	Other: Biological sample collection; Collection of biological samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Invasion	Distance travelled by glioma stem cells into brain organoids	through study completion, an average of 4 years
Gene assessment	Identification of genes responsible of GSC invasion, among those reportedly involved in self-renewal and ciliogenesis	through study completion, an average of 4 years

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Collaborators: Catholic University of the Sacred Heart; Heinrich-Heine University, Duesseldorf; Istituto Superiore di Sanità

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2018
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: February 23, 2023
• First Submitted That Met QC Criteria: March 6, 2023
• First Posted (Actual): March 16, 2023

Study Record Updates

• Last Update Posted (Actual): March 16, 2023
• Last Update Submitted That Met QC Criteria: March 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: glioma stem-like cells; brain organoids; brain invasion; ciliogenesis
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Glioma
• Other Study ID Numbers: 2253

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No