Novel Molecular Targets and Innovative Therapeutic Perspective in Medulloblastoma

NCT06959979 | Recruiting Early Phase 1

• 1 other identifier: PNRR-TR1-2023-12378243
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Medulloblastoma (MB), a rare yet critical pediatric brain tumor, is divided into 4 molecular subgroups (WNT, SHH, Group 3, Group 4), each with distinct genetic profiles. Despite diagnostic and therapeutic advances, neurotoxicity from standard treatments (resection, radiotherapy, chemotherapy) and the need for long-term care remain challenges. CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib), approved for breast cancer, show potential in other tumors, but their efficacy in MB is unclear. Treatment resistance is a concern. This project aims to identify genetic markers of sensitivity to CDK4/6 inhibitors in MB, to improve therapies and overcome resistance.

Conditions

Medulloblastoma, Childhood

Outcome Measures

Primary Outcomes (8)

• Clarify the molecular mechanisms underlying the acquisition of resistance to CDK4/6i in MB.

  Genetic characterization of PDOs derived from patients with medulloblastoma (MB). Measurement: Analysis of the mutational status of over 500 genes using TSO-500 sequencing, comparing the genetic profiles of PDOs with those of primary tumors.

  2 yrs

• Clarify the molecular mechanisms underlying the acquisition of resistance to CDK4/6i in MB.

  Assessment of changes in cell proliferation in patient-derived organoids (PDOs) from medulloblastoma (MB) treated with CDK4/6 inhibitors compared to untreated controls. Measurement: Quantified by cell counting assays.

  2 years

• Clarify the molecular mechanisms underlying the acquisition of resistance to CDK4/6 inhibitors in medulloblastoma (MB).

  Histological characterization of PDOs derived from patients with medulloblastoma (MB). Measurement: Evaluation of the expression of MB-specific histological markers by immunohistochemistry, comparing expression patterns between PDOs and primary tumors.

  2 years

• Clarify the molecular mechanisms underlying the acquisition of resistance to CDK4/6i in MB.

  Assessment of changes in cell survival in patient-derived organoids (PDOs) from medulloblastoma (MB) treated with CDK4/6 inhibitors compared to untreated controls. Measurement: Quantified by cell viability assays.

  2 years

• Clarify the molecular mechanisms underlying the acquisition of resistance to CDK4/6i in MB.

  Assessment of changes in cellular senescence levels in patient-derived organoids (PDOs) from medulloblastoma (MB) treated with CDK4/6 inhibitors compared to untreated controls. Measurement: Evaluated by analysis of senescence markers.

  2 years

• Clarify the molecular mechanisms underlying the acquisition of resistance to CDK4/6i in MB.

  Outcome Measure Title: Quantitative change in cell proliferation Description: Quantitative change in cell proliferation expressed as a percentage variation from baseline. Unit of Measure: Percent change from baseline (%).

  2 years

• Clarify the molecular mechanisms underlying the acquisition of resistance to CDK4/6i in MB.

  Outcome Measure Title: Quantitative change in cell survival Description: Quantitative change in cell survival expressed as a percentage variation from baseline. Unit of Measure: Percent change from baseline (%).

  2 years

• Clarify the molecular mechanisms underlying the acquisition of resistance to CDK4/6i in MB.

  Outcome Measure Title: Quantitative change in cellular senescence Description: Quantitative change in cellular senescence expressed as a percentage variation from baseline. Unit of Measure: Percent change from baseline (%).

  2 years

Secondary Outcomes (4)

• CDK4/6 inhibitor-resistant clones

  2 years

• transcriptomic analysis

  2 years

• Evaluate new therapeutic strategies

  2 years

• Quantification of fluorescence intensity for tumor marker detection using synthetic DNA nanoswitches in histological sections from medulloblastoma patients and patient-derived organoids (PDOs)

  2 years

Study Arms (2)

Prospective

EXPERIMENTAL

To establish ex-vivo translational models of MB, we will develop patient-derived organoids (PDOs) from primary surgical biopsies of patients

Drug: CDK4/6 Inhibitor (Palbociclib, Ribociclib, Abemaciclib)

Retrospective

EXPERIMENTAL

To establish ex-vivo translational models of MB, we will develop patient-derived organoids (PDOs) from primary surgical biopsies of patients

Drug: CDK4/6 Inhibitor (Palbociclib, Ribociclib, Abemaciclib)

Interventions

CDK4/6 Inhibitor (Palbociclib, Ribociclib, Abemaciclib) DRUG

Evaluation of the response to CDK4/6 inhibitors (Palbociclib, Ribociclib, Abemaciclib) on selected Medulloblastoma (MB) patient-derived organoids (PDOs).

Also known as: We will then evaluate the effects of CDK4/6 inhibitors on the selected MB PDOs.

Prospective; Retrospective

Eligibility Criteria

• Age: 0 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• All patients affected by Medulloblastoma operated on at the Pediatric Neurosurgery Unit during their pediatric age will be elected to take part to the study

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead
• University of Rome Tor Vergata: collaborator
• Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello: collaborator
• Università degli Studi di Enna Kore: collaborator

Study Sites (1)

Fondazione Policlinico Gemelli Irccs

Roma, ROMA, 00151, Italy

RECRUITING

MeSH Terms

Conditions

Medulloblastoma

Interventions

palbociclib; ribociclib; abemaciclib

Condition Hierarchy (Ancestors)

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

Central Study Contacts

GIANPIERO TAMBURRINI, MD

CONTACT

3349468776; gianpiero.tamburrini@unicatt.it

MARIA CONCETTA GELOSO, PHD

CONTACT

mariaconcetta.geloso@unicatt.it

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Model Details: Prospective, non-drug, non-device interventional study with molecular analysis on biological samples including a retrospective component. No patient procedures will be performed other than those within standard clinical practice. Specifically, the tumor will be collected during surgical removal and partially processed for organoid development, with the remainder stored for subsequent molecular comparisons between the organoid and the original tissue.

Study Record Dates

• First Submitted: July 24, 2024
• First Posted: May 7, 2025
• Study Start: November 25, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: May 7, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)