Glioblastoma Evaluation for Heterogeneity In RadioseNsitivity (GEHIRN)

Glioblastoma Evaluation for Heterogeneity In RadioseNsitivity (GEHIRN): Preclinical Observational Study on Ex-vivo Surgical Specimens

This is an observational study on GBM surgical samples to investigate if increasing doses of radiation therapy could improve the radiation response; and in particular the investigators will assess if there is a correlation between the number of the phosphorylated H2AX nuclear foci and the different dose level of radiation therapy.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Radiation: radiation of brain tissue specimen and dna damage analysis

Detailed Description

Standard of care for newly diagnosed glioblastoma (GBM) patients consists of surgical resection followed by radiotherapy with concurrent and adjuvant Temozolomide chemotherapy. Despite these treatments, the prognosis remains poor. Nevertheless, preliminary data on GBM patients show variable outcomes related to a different treatment response, that could be related to the GBM intrinsic heterogeneity, but also to a different patient sensitivity to radiation therapy.

The assessment of this individual radio-sensitivity may provide valuable data to define more tailored treatment schedules, that could potentially be more effective.

Published studies on small cohort of patients show that a possible system to investigate the tumor radiation sensitivity, is to monitor the cellular DNA damage after tissue irradiation, that correlates with the survival fraction of in vitro tumor cells; the DNA damage could be identified through the quantification of Phosphorylated histone H2AX nuclear foci that correlate with the unrepaired DNA double strand breaks (DSBs).

Based on this background, The investigators designed an observational study on GBM surgical samples to investigate if increasing doses of radiation therapy could improve the radiation response; and in particular they will assess if there is a correlation between the number of the phosphorylated H2AX nuclear foci and the different dose level of radiation therapy.

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

• Study Contact: Name: Luisa Bellu, MD; Phone Number: +39 0282248536; Email: luisa.bellu@humanitas.it

Study Locations

• Italy
  • Milan
    • Rozzano, Milan, Italy, 20089
      • Recruiting
      • Humanitas Clinical Institute
      • Contact: Luisa Bellu, MD; Phone Number: +39 0282248536; Email: luisa.bellu@humanitas.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

• Sampling Method: Non-Probability Sample

Study Population

Glioblastoma Patients eligible for surgical procedure.

Description

Inclusion Criteria:

• Patients aged >18 years
• Patients eligible for diagnostic or therapeutic surgical procedure
• Written informed consent
• Histopathologically confirmed newly diagnosed glioblastoma according to WHO 2021
• Availability of fresh tissue samples

Exclusion Criteria:

• Other extra-cranial cancer
• Non GBM glioma
• Previous brain radiation therapy

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of distribution of number of γH2AX foci in each irradiated specimen (Nfoci) for each radiation dose level	Number of foci per irradiated sample (Nfoci) for each dose level expressed as [(number of observed γH2AX foci per selected dose level)-(number of observed γH2AX foci in control unirradiated sample)].	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
correlation between n° of γH2AX foci and dose levels	this correlation will be described by the slope for each sample Nfoci at increasing dose levels	1 month

Collaborators and Investigators

• Sponsor: Istituto Clinico Humanitas

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: September 22, 2022
• First Submitted That Met QC Criteria: September 22, 2022
• First Posted (Actual): September 27, 2022

Study Record Updates

• Last Update Posted (Actual): October 6, 2022
• Last Update Submitted That Met QC Criteria: October 4, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: 3075

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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