Patient-derived Glioma Stem Cell Organoids

NCT04868396 | Active Not Recruiting

• 1 other identifier: Glioma stem cell organoids
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

Rationale: Glioblastoma (GM) is the most frequent incurable adult brain tumor with median survival of 15 months after diagnosis, despite extensive treatment with surgery, radiation therapy and chemotherapy. Tumor recurrence is inevitable after which life prolonging therapies are no longer available. The development of new treatments for GM is being hampered by inter-and intratumoral heterogeneity of tumors and their microenvironment, which currently cannot be predicted accurately with current diagnostics. Objective: To establish primary patient derived organoid cultures from GM to study mechanisms that contribute to aggressive tumor growth and treatment resistance in primary and recurrent GM. Study design: Preclinical study, using patient derived glioblastoma tissue. Study population: Patients 18 years or older, with newly diagnosed glioblastoma. Main study parameters/endpoints: Intra-and inter organoid genetic and epigenetic heterogeneity that is representative for GM. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Minimal burden, since the biopsies are part of a regular neurosurgical procedure (debulking); which intends to eradicate the macroscopical tumorload in order to optimize survival benefit. The tissue (biopsy) that will be used for this trial is part of the tumor tissue that is resected during the standard debulking. Benefit: no benefit for the patient.

Conditions

Glioblastoma

Keywords

Stem cells; Organoids

Outcome Measures

Primary Outcomes (4)

• Organoid cultures

  Primary derived organoid cultures from GM

  Baselline

• Long term culturing and biobanking conditions for GM organoids

  Determine the frequency of primary, secondary and tertiary organoid formation, size distribution of the organoids, the rate of proliferation and cell death will be calculated.

  Baseline

• Intra-organoid heterogeneity reflects intra-tumoral genetic and epigenetic heterogeneity

  To assess whether intra-organoid heterogeneity reflects intra-tumoral genetic and epigenetic heterogeneity; with initial focus on MGMT promoter methylation status

  Baseline

• GM organoid model

  GM organoid model that reflects primary and secondary temozolomide resistance

  Baseline

Secondary Outcomes (3)

• Define oncogenic drivers

  Baseline

• Organoid platform

  Baseline

• ctDNA

  Baseline

Study Arms (1)

Glioblastoma patients

Glioblastoma patients selected to undergo surgical removal of a glioblastoma (based on MRI image).

Procedure: Tumor biopsy

Interventions

Tumor biopsy PROCEDURE

Tumor material will be derived from 'left-over' tumor tissue that is not needed for standardised diagnostics (immune histochemistry and molecular testing).

Glioblastoma patients

Eligibility Criteria

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

Study Population

All these patients regardless of sex and ethnicity will be asked to co-operate in this study. The patients will be consecutively included.

You may qualify if:

• MRI imaging suggestive for glioblastoma
• \> 18 years of age

You may not qualify if:

• Karnofsky index \< 70
• Clotting disorders
• Neurosurgical contraindications for gross total resection

Sponsors & Collaborators

• Maastricht Radiation Oncology: lead

Study Sites (2)

Maastricht UMC+

Maastricht, Limburg, 6202AZ, Netherlands

Location

Maastricht Radiation Oncology

Maastricht, Limburg, 6229ET, Netherlands

Location

Biospecimen

Retention: SAMPLES WITH DNA

Tumor biopsies taken during surgery Blood sample

MeSH Terms

Conditions

Glioblastoma

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

Study Officials

• Marc Vooijs, Prof. Dr.

  Maastro Radiaton Oncology

  PRINCIPAL INVESTIGATOR

• A. Hoeben, Dr.

  Maastricht UMC+

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2021
• First Posted: April 30, 2021
• Study Start: April 10, 2021
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: November 20, 2024

Record last verified: 2024-11

Locations

NL (2)