Biomarkers for Prognosis of Glioblastoma (GBM)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2011 by University of Nebraska
Sponsor:
Information provided by (Responsible Party):
University of Nebraska
ClinicalTrials.gov Identifier:
NCT01493219
First received: December 13, 2011
Last updated: December 14, 2011
Last verified: December 2011
  Purpose

The purpose of this study is:

  1. To learn if (MMP-2, MMP-9 and NGAL) which are substances found in blood and urine associated with tumors, can be used as tumor markers in the management and treatment of glioblastoma.
  2. To study the relationship between MMP-2, MMP-9 and NGAL with quality of life and disease symptoms.

Condition
Glioblastoma

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: MMP-2, MMP-9 and NGAL as Biomarkers for Glioblastoma (GBM) Biomarkers for the Prognosis of Glioblastoma

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • To estimate the amount of MMP-2, MMP-9 and MMP-9/NGAL using immunohistochemistry in tumor tissue and non-tumor (epilepsy) patients. [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    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.

  • To provide preliminary evidence that MMP-2, MMP-9 and MMP-9/NGAL in tissue corresponds with their presence in the urine and blood in patients undergoing surgery for epilepsy (Aim 1a) and in patients with grade IV glioma (Aim 1b). [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    For each outcome (MMP-2, MMP-9 and MMP-9/NGAL), Pearson's correlation coefficient will be used to examine the association between 1) tissue and urine and 2) tissue and blood. Spearman's correlation will be used in the event that the data are not normally distributed and a suitable transformation is not evident. Due to the anticipated interaction of group with presence of these biomarkers, these analyses will be conducted separately for epilepsy control patients and GBM patients.

  • To examine the association between the change in urine and serum MMP-2, MMP-9 and MMP-9/NGAL levels with changes in tumor burden. [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    For each outcome (MMP-2, MMP-9 and MMP-9/NGAL), Pearson's correlation coefficient will be used to examine the association between 1) tissue and urine and 2) tissue and blood. Spearman's correlation will be used in the event that the data are not normally distributed and a suitable transformation is not evident. Due to the anticipated interaction of group with presence of these biomarkers, these analyses will be conducted separately for epilepsy control patients and GBM patients

  • To descriptively examine quality of life (QOL) measurements and symptoms measurements. [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    QOL and symptoms measurements will be descriptively summarized using means, medians, standard deviations, and ranges (for continuous data) and frequencies and percentages (for categorical data), along with corresponding 95% confidence intervals.

  • To estimate the association of post-operative biomarker levels with time to progression (TTP) and overall survival (OS). [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    As an exploratory analysis, the association of MMP-2, MMP-9 and MMP-9/NGAL at 24h and 48h post-op will be summarized examined using a Cox-proportional hazards regression model


Biospecimen Retention:   Samples Without DNA

Whole Blood, Urine, and Tissue.


Estimated Enrollment: 30
Study Start Date: September 2011
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Epilepsy
Glioma

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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

Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01493219

Contacts
Contact: Nicole Shonka, MD 402-559-5520 nshonka@unmc.edu
Contact: Alice Kueh, MS 402-559-8511 akueh@unmc.edu

Locations
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Alice Kueh, MS    402-559-8511    akueh@unmc.edu   
Principal Investigator: Nicole Shonka, MS         
Sponsors and Collaborators
University of Nebraska
Investigators
Principal Investigator: Nicole Shonka, MD UNMC
  More Information

No publications provided

Responsible Party: University of Nebraska
ClinicalTrials.gov Identifier: NCT01493219     History of Changes
Other Study ID Numbers: IRB 369-11-FB
Study First Received: December 13, 2011
Last Updated: December 14, 2011
Health Authority: United States: University of Nebraska Medical Center

Keywords provided by University of Nebraska:
Glioblastoma
Glioblastoma Multiforme
Astrocytoma
Gliosarcoma
Glioma WHO grade IV

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on August 19, 2014