MMP-2, MMP-9 and NGAL as Biomarkers for Glioblastoma (GBM) Biomarkers for the Prognosis of Glioblastoma
19 Years
N/A
Both
Glioblastoma
Trial Information
MMP-2, MMP-9 and NGAL as Biomarkers for Glioblastoma (GBM) Biomarkers for the Prognosis of Glioblastoma
Matrix metalloproteinases (MMP) -2 and -9 belong to a multigene family of degradative
enzymes implicated in the neoangiogenesis required for tumor growth. In the central nervous
system (CNS), MMP-2, MMP-9 and neutrophil gelatinase-associated lipocalin (NGAL) are
overexpressed in orthotopic models and also in human brain tumor specimens. Furthermore,
serum and urinary levels of these markers have been shown to correlate with the presence and
status of brain tumors in all types of primary brain tumors. A major challenge in the
treatment of primary brain tumors is the dependence on magnetic resonance imaging (MRI) to
differentiate disease progression from treatment-related change. This is particularly
challenging in glioblastomas (GBM) where multimodality therapy with radiation and
chemotherapy is commonly used and can lead to pseudoprogression and treatment-related tissue
necrosis, both of which can masquerade as true tumor progression. Often we are faced with
the decision to treat based on imaging findings alone or to recommend that patients have
another invasive surgery. We hypothesize that MMP-2, MMP-9 and NGAL will: 1) be detected
on tumor tissue by immunohistochemistry and not on non-tumor (epilepsy) brain tissue, 2)
parallel the course of disease in the urine and/or serum of patients and 3) remain unchanged
in the event of pseudoprogression and treatment related imaging changes. Quality of life,
patient symptoms, and cognitive function are vitally important in patients with GBM.
Quality of life and selected symptoms will also be assessed and correlated with serum and
urine biomarkers. We hope to confirm the utility of MMP-2, MMP-9 and NGAL in the management
of GBM.
Inclusion Criteria:
1. Subjects scheduled for a surgical excision or biopsy as ordered by his/her clinic or
inpatient physician for epilepsy OR subjects newly diagnosed with high grade (grade
IV) glioma (The performance of this procedure will be under standard of care surgical
guidelines.)
- non-tumor tissue controls from subjects undergoing surgery for epilepsy
- tumor tissue from subjects undergoing surgery for grade IV glioma
2. Epilepsy subject identified as a control undergoing surgery must willingly provide
pre-op and post-op serum and urine samples for research
3. GMB subject must willingly provide blood and urine samples pre-op and post-op as
well as blood and urine samples for research and QOL measurements taken at protocol
specific time points
4. GBM subject plans to receive clinical care visits which coincide with MRIs and/or
with a change in symptoms and any secondary surgical resections and/or biopsies
solely at UNMC/TNMC
5. Subjects must willingly give signed informed consent
6. Age 19 years or older (the age of consent in Nebraska)
7. Women must not be pregnant due to teratogenic effects of MRI
Exclusion Criteria:
1. Inability to fulfill the requirements of the protocol
2. No serious disease or condition that, in the opinion of the investigator, would
compromise the patient's ability to participate in the study
3. Known to be positive for HIV or infectious hepatitis, type A, B or C or active
Hepatitis
4. Subjects newly diagnosed with high grade (grade IV) glioma (GBM) unable to be
followed by MRI due to
- Pacemaker
- Chronic kidney disease stage 3-5 (Glomerular Filtration Rate <60)
- Unable to lay flat for 90 minutes
- Any metallic foreign body not approved for MRI
- Known hypersensitivity to Gadolinium contrast or other required for MRI
Type of Study:
Observational
Study Design:
Observational Model: Case Control, Time Perspective: Prospective
Outcome Measure:
To estimate the amount of MMP-2, MMP-9 and MMP-9/NGAL using immunohistochemistry in tumor tissue and non-tumor (epilepsy) patients.
Outcome Description:
The mean MMP-2, MMP-9 and NGAL will be estimated using 95% confidence intervals, for the GBM and control groups. In the event that the data are not normally distributed and a suitable transformation is not evident, the median and a 95% confidence for a median will be used.
Outcome Time Frame:
Up to 3 years
Safety Issue:
No
Principal Investigator
Nicole Shonka, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
UNMC
Authority:
United States: University of Nebraska Medical Center
Study ID:
IRB 369-11-FB
NCT ID:
NCT01493219
Start Date:
September 2011
Completion Date:
September 2016
Related Keywords:
- Glioblastoma
- Glioblastoma
- Glioblastoma Multiforme
- Astrocytoma
- Gliosarcoma
- Glioma WHO grade IV
- Glioblastoma
Name | Location |
|---|---|
| University of Nebraska Medical Center | Omaha, Nebraska 68198-3330 |
