Glioblastoma: Validation and Comparison Between Primary Tumor and Its Murine Model

NCT02904525 | Unknown

• 1 other identifier: 268/14
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Despite maximal safe surgery followed by combined chemo-radiation therapy, the outcome of patients suffering from glioblastoma (GBM) remains extremely poor with a median survival of 15 months. Hence, new avenues have to be taken to improve outcome in this devastating disease. Given their intracerebral localization and their highly invasive features, GBM pose some specific challenges for the development of adequate tumor models. Orthotopic xenograft models directly derived from the tumor of a patient might represent an attractive perspective to develop patient-specific targeted therapies. This approach remains however to be validated for GBM as it offers specific challenges, including the demonstration that the properties of xenograft models validly represent treatment relevant features of the respective human tumors. In this innovative project the investigators aim to compare and validate an approach of paired human GBM and respective derived orthotopic xenografts in the mouse brain on the levels of radiological behavior and metabolism of the tumors, as determined by high resolution MRI of the patients (7T MRI) and the respective orthotopic mouse xenografts (14.1T MRI), as well as on the level of the transcriptome, genome, and methylome of the original GBM tissue and respective derived xenografts/glioma sphere lines. The data will be integrated in multidimensional analyses and interrogated for similarities and associations with molecular GBM subtype. This pilot project will provide the basis for the crucial next steps, which will include drug intervention studies. New promising drugs, tested pre-clinically in the mouse orthotopic xenograft models established here using the radiologic/metabolic/molecular procedures described for this project, will be taken into patients in phase 0 studies. GBM patients will receive radiologic/metabolic follow-up using high resolution MRI under drug treatment, followed by resection of the tumor and subsequent acquisition of molecular data.

Conditions

Glioblastoma

Keywords

newly diagnosed; MRI

Outcome Measures

Primary Outcomes (2)

• GBM metabolites using high resolution spectroscopy

  High resolution spectroscopy metabolite analysis of GBM

  2 years

• Next generation sequencing of GBM tumor tissue

  Molecular comparison of primary GBM tumor and paired orthotropic xenograft

  2 years

Study Arms (1)

7T MRI + high resolution spectroscopy

EXPERIMENTAL

Next to routine imaging, patients undergo an additional 7 tesla MRI for high resolution spectroscopy

Device: 7 Tesla MRI, no contrast agent

Interventions

7 Tesla MRI, no contrast agent DEVICE

Patients with newly diagnosed glioblastoma undergo a 7Tesla MRI

7T MRI + high resolution spectroscopy

Eligibility Criteria

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

You may qualify if:

• High level of suspicion of glioblastoma
• Planned neurosurgical resection
• Adequate bone marrow function
• Adequate liver and kidney function

You may not qualify if:

• inability to undergo MRI
• inability to undergo neurosurgical resection

Sponsors & Collaborators

• Andreas Hottinger: lead
• Ecole Polytechnique Fédérale de Lausanne: collaborator

Study Sites (1)

CHUV, University Hospital Lausanne

Lausanne, Canton of Vaud, 1066, Switzerland

RECRUITING

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

• Andreas F Hottinger, MD-PhD

  CHUV Lausanne University Hospital

  STUDY CHAIR

Central Study Contacts

Andreas F Hottinger, MD-PhD

CONTACT

+41 21 314 0168; andreas.hottinger@chuv.ch

Laurence Benoit

CONTACT

+41 21 314 0168; laurence.benoit@chuv.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PI- Sponsor

Study Record Dates

• First Submitted: March 11, 2016
• First Posted: September 19, 2016
• Study Start: June 1, 2015
• Primary Completion: January 27, 2021
• Study Completion: April 30, 2021
• Last Updated: January 27, 2021

Record last verified: 2021-01

Locations

CH (1)