Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Disease Progression and Treatment-induced Alterations in Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02152748
Recruitment Status : Unknown
Verified March 2017 by Adelheid Wöhrer, Medical University of Vienna.
Recruitment status was:  Active, not recruiting
First Posted : June 2, 2014
Last Update Posted : March 22, 2017
Sponsor:
Information provided by (Responsible Party):
Adelheid Wöhrer, Medical University of Vienna

Brief 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.


Condition or disease Intervention/treatment
Brain Tumor Genetic: analyze systematically morphological and molecular changes associated with glioblastoma progression and therapy-resistance

Detailed 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.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 60 participants
Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: Analysis of Disease Progression and Treatment-Induced Alterations in Glioblastoma - an Integrative Morphological and Molecular Approach
Study Start Date : April 2014
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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.
Genetic: analyze systematically morphological and molecular changes associated with glioblastoma progression and therapy-resistance



Primary Outcome Measures :
  1. Morphology- based analysis [ Time Frame: 24 months ]
    Histopathological workup and evaluation

  2. Molecular analysis [ Time Frame: 24 months ]
    Assessment of genomic alterations at DNA-, RNA- and methylation level


Biospecimen Retention:   Samples With DNA
Tissue


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
All newly diagnosed GB patients will be identified in the Austrian population since 2007 - after the current firstline therapy has become standard, in order to warrant a homogenously treated patient cohort. GB patients with multiple resections will be identified.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02152748


Locations
Layout table for location information
Austria
Medical University of Vienna, Institute of Neurology
Vienna, Austria, 1090
Sponsors and Collaborators
Medical University of Vienna
Investigators
Layout table for investigator information
Principal Investigator: Adelheid Wöhrer, MD PhD Medical University Vienna

Layout table for additonal information
Responsible Party: Adelheid Wöhrer, Dr.med.univ et scient.med., Medical University of Vienna
ClinicalTrials.gov Identifier: NCT02152748     History of Changes
Other Study ID Numbers: KLI 394
First Posted: June 2, 2014    Key Record Dates
Last Update Posted: March 22, 2017
Last Verified: March 2017
Keywords provided by Adelheid Wöhrer, Medical University of Vienna:
glioblastoma
morphological and molecular changes
progression
therapy-resistance
Additional relevant MeSH terms:
Layout table for MeSH terms
Glioblastoma
Disease Progression
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Disease Attributes
Pathologic Processes