Disease Progression and Treatment-induced Alterations in Glioblastoma

Brain Tumor Clinical Trial

Official title:

Analysis of Disease Progression and Treatment-Induced Alterations in Glioblastoma - an Integrative Morphological and Molecular Approach

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02152748
• Other study ID #: KLI 394
• Status: Active, not recruiting
• Phase: N/A
• First received: May 22, 2014
• Last updated: March 21, 2017
• Start date: April 2014
• Est. completion date: December 2017

Study information

• Verified date: March 2017
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Summary of scientific evidence and rationale of this project:

Integrative molecular-genetic approaches have provided important insights in the biology of glioblastoma. It has meanwhile become clear, that glioblastoma is not a single tumor entity but comprises different molecular subtypes, which are associated with a distinct genetic/epigenetic signature and prognosis. Multimodal treatment approaches combining radio- and chemotherapy as well as the recent introduction of novel antiangiogenic agents have resulted in increasing survival times and improved quality-of-life of glioblastoma patients. Yet, despite these intense treatment efforts the therapeutic efficacy in glioblastoma patients is limited, leading in virtually all cases to tumor recurrence and death of the patients.

As only a limited fraction of glioblastoma patients undergo second neurosurgery at tumor recurrence (< 10%), post-therapeutic samples are rare and no systematic, large-scale studies exist, which address post-therapeutic morphological and molecular alterations in glioblastoma tumor tissue. Yet, these data would help to improve the understanding of mechanisms involved in therapy-resistance and tumor progression, to develop new therapeutic approaches and could pave the way for personalized treatment strategies.

Description:

Objectives of the project:

The aim of this study is to analyze systematically morphological and molecular changes associated with glioblastoma progression and therapy-resistance in matched pre- and post-therapeutic glioblastoma samples.

The following primary aims will be addressed:

1. Morphological characterisation of changes in a large series of matched glioblastoma tissues pertaining to i. Vascularization and hypoxia-mediated factors ii. Tumor necrosis and chemoradiation-induced necrosis iii. Inflammatory response iv. Tumor cellularity and proliferation v. Tumor cell phenotype after treatment e.g. glial-mesenchymal transition

2. Molecular analyses

i. Transcriptomic, DNA methylation and genomic profiling will be performed to detect changes in gene expression, methylation and copy number aberrations in post-therapeutic as compared to pre-therapeutic tumor tissue. ii. The relationship between the transcriptomic, DNA methylation and genomic profiles will be analyzed.

3. Exploratory analysis of associations between morphological and molecular changes in a screening set of 30 glioblastoma cases (with available fresh frozen tissues at first and second surgery) and subsequent validation of relevant findings in a larger glioblastoma cohort (150 cases with matched formalin-fixed paraffin-embedded tissues) by appropriate methods including immunohistochemistry, fluorescence-in-situ-hybridization, and sequencing.

4. Special attention will be paid to gender-specific patterns of therapy-related changes and tumor progression.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Related Conditions & MeSH terms

• Brain Tumor
• Disease Progression
• Glioblastoma

Intervention

Genetic:
• analyze systematically morphological and molecular changes associated with glioblastoma progression and therapy-resistance

Locations

Country	Name	City	State
Austria	Medical University of Vienna, Institute of Neurology	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Morphology- based analysis	Histopathological workup and evaluation	24 months
Primary	Molecular analysis	Assessment of genomic alterations at DNA-, RNA- and methylation level	24 months