Disease Progression and Treatment-induced Alterations in Glioblastoma

NCT ID: NCT02152748

Last Updated: 2017-03-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-04-30

Study Completion Date

2017-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Brain Tumor

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

RETROSPECTIVE

Study Groups

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Glioblastoma

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.

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

Intervention Type GENETIC

Interventions

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

Intervention Type GENETIC

Eligibility Criteria

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Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medical University of Vienna

OTHER

Sponsor Role lead

Responsible Party

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Adelheid Wöhrer

Dr.med.univ et scient.med.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Adelheid Wöhrer, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Medical University Vienna

Locations

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Medical University of Vienna, Institute of Neurology

Vienna, Vienna, Austria

Site Status

Countries

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Austria

Other Identifiers

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KLI 394

Identifier Type: -

Identifier Source: org_study_id

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