Patient's Derived Organoids for Drug Screening in Glioblastoma

NCT06781372 | Not Yet Recruiting

• 1 other identifier: 6489
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The study will enroll patients suffering from glioblastoma, a malignant brain tumor. Intervention is intended as a laboratory intervention and not as a clinical intervention. In fact, tumor removed from patients' brains will be sent to a dedicated laboratory to obtain an "avatar" of the tumor, named patient-derived organoid (PDO). A number of experimental antitumor approaches will be studied on PDOs. Results of these experiments will be correlated to the prognosis of patients.

Conditions

Glioblastoma; Glioblastoma Multiforme (GBM); Glioblastoma Multiforme, Adult

Keywords

glioblastoma; patient derived organoid; transposable elements; splicing; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Histopathological PDO and tumor evaluation

  The histopathological resemblance of PDOs to primary tumor will be rated semiquantitatively (0-10). The efficacy of treatment on PDOs will be rated using the % of dead cells.

  From enrollment to 36 months

Secondary Outcomes (1)

• Histopatological primary and recurrent PDO evaluation.

  From enrollment to 36 months

Study Arms (1)

PDO arm

EXPERIMENTAL

Tumor tissue from enrolled patients will be collected and used to generate PDOs.

Biological: Development and characterization of PDOs; Biological: Evaluation of the effects of epigenetic and splicing inhibitors on viability and gene expression signatures of GBM PDOs and GSCs

Interventions

Development and characterization of PDOs BIOLOGICAL

An amount of tissue of approximately 2-3 cm3, if available, will be allocated to the study. The specimen will be divided in three parts (depending on the volume of the biopsy) and used to: a) obtain PDOs according to established procedures (Chadwick, et al., 2020; Gamboa, et al., 2021); b) flash-frozen for molecular analysis of original tissue; c) used to isolate GSCs by flow-cytometry cell sorting. Only PDOs characterized by histological and molecular conformity with primary tumors will be used. The mutational status of genes frequently associated with GBM onset and progression will be analyzed in PDOs, and compared with data derived from tumor DNA, in order to assess their representation of the genetic heterogeneity of original tumors. These studies will allow us the set up a reliable procedure for the ex-vivo establishment of pre-clinical models of GBM.

PDO arm

Evaluation of the effects of epigenetic and splicing inhibitors on viability and gene expression signatures of GBM PDOs and GSCs BIOLOGICAL

PDOs and GSCs representing different GBM molecular subtypes will be treated with epigenetic modulators , with spliceosome inhibitors or with drugs that indirectly target the splicing machinery, such as PRMT5 inhibitors. These drugs will be tested for their ability to suppress growth and/or induce cell death, when administered either alone or in combination with standard chemotherapy. Furthermore, the investigators will perform RNA sequencing experiments to identify TE-derived transcripts and splice variants induced by the treatments. By employing a computational pipeline developed in our laboratory (Pieraccioli and Sette, unpublished), the investigators will also characterize the affinity for MHC-I and immunogenicity of neoepitopes encoded by the treatment-induced TE-derived transcripts and splice variants. The results of these analysis will allow to identify neoepitopes to be used for designing immunotherapy approaches.

PDO arm

Eligibility Criteria

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

You may qualify if:

• adult patients undergoing resective neurosurgery for glioblastoma, IDH-wildtype

You may not qualify if:

• Needle biopsies
• Age \<18 years
• Inability to give informed consent
• Brain surgery for tumor disease other than GBM
• Previous neoadjuvant chemotherapy or radiotherapy

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, 00168, Italy

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Growth and Development

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Physiological Phenomena

Study Officials

• Alessandro Olivi, M.D.

  Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

• Claudio Sette, PhD

  Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alessandro Olivi, M.D.

CONTACT

+390630154120; alessandro.olivi@policlinicogemelli.it

Q. Giorgio D'Alessandris, M.D.

CONTACT

+390630155414; quintinogiorgio.dalessandris@policlinicogemelli.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: It is a clinical laboratory study enrolling glioblastoma patients.

Study Record Dates

• First Submitted: January 7, 2025
• First Posted: January 17, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2028
• Last Updated: March 13, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)