MRI Study With Ferumoxytol in Assessing Early Response in Patients With Glioblastoma Multiforme Receiving Temozolomide and Radiation Therapy

Study Overview
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Brief Summary
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This pilot clinical trial studies how a magnetic resonance imaging (MRI) study with ferumoxytol works as a contrasting agent in assessing early response in patients with glioblastoma multiforme receiving temozolomide and radiation therapy. Ferumoxytol is a very small form of iron particles that are injected into the body and taken up by certain tissues which may make these tissues easier to see during imaging. Diagnostic procedures, such as an MRI study with ferumoxytol, may help measure a patient's response to earlier treatment.

Detailed Description
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PRIMARY OBJECTIVES: I. To characterize glioblastoma multiforme (GBM) tumor vascular properties using ferumoxytol (ferumoxytol non-stoichiometric magnetite) and compare to those obtained using gadolinium (Gd) based MRI contrast agent. II. To characterize vascular changes in GBM tumors associated with standard radio/chemotherapy. SECONDARY OBJECTIVES: I. Cerebral blood flow (CBF), mean transit time (MTT), and time-to-peak (TTP) perfusion parameters will be measured for each contrast agent and evaluated in post-hoc analysis. II. To obtain qualitative assessment of tumor vascularity using time-of-flight (TOF) magnetic resonance (MR) angiography techniques. III. To characterize changes in the apparent diffusion coefficient (ADC) of tumor water associated with standard radio/chemotherapy in GBM. OUTLINE: Patients receive gadolinium intravenously (IV) on day 1 and ferumoxytol non-stoichiometric magnetite IV on day 2 then undergo dynamic susceptibility contrast enhanced (DSC) MRI, and dynamic contrast enhanced (DCE) MRI, diffusion-weighted imaging (DWI) (day 1 only), and TOF MR angiography on days 1-3 at 4 time points: before radiation, 3 weeks after initiation of radiation plus temozolomide, at the end of radiation (6 weeks post first dose) and 6 weeks after radiation (12 weeks post first dose). Ferumoxytol non-stoichiometric magnetite administration continues in the absence of unacceptable toxicity. Patients also receive temozolomide and undergo radiation therapy per standard of care. After completion of ferumoxytol non-stoichiometric magnetite administration, patients are followed up for 4-6 weeks and then periodically until the resolution or stabilization of unacceptable toxicities.

Official Title
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Early Assessment of Tumor Response to Therapy Using Ferumoxytol (Code 7228) as an MR Contrast Agent in Patients With Glioblastoma Multiforme (MedDRA Code 10018337)

Conditions
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Adult Brain Glioblastoma

Intervention / Treatment
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* Drug: Gadolinium
* Drug: Ferumoxytol Non-Stoichiometric Magnetite
* Other: Dynamic Contrast-Enhanced Magnetic Resonance Imaging
* Other: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging
* Other: Diffusion Weighted Imaging
* Other: MRI-Based Angiogram


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have radiologically and histologically confirmed diagnosis of glioblastoma multiforme Patients must have measurable disease, defined as evident tumors with gadolinium enhancement on MRI that is measurable in at least one diameter and visible on both axial and sagittal or coronal views Life expectancy of greater than 6 months Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 50%) Patients scheduled for standard therapy (6 weeks radiation therapy (RT)   60 Gy, plus temozolomide 75 mg/m^2 during 6 week [w] RT, and followed routine monthly temozolomide therapy) Patients must be on a stable or decreasing dose (up to 8 mg daily) of dexamethasone throughout the study After entry into the study, patients are expected to be followed for at least 1 month after the last infusion of ferumoxytol Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign a written informed consent document; all patients, or their legal guardians, must sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization in accordance with institutional guidelines Exclusion Criteria: Patients who have had chemotherapy or radiotherapy Patients may not be receiving any other investigational agents History of allergic reactions attributed to compounds of similar chemical or biologic composition to ferumoxytol: parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations (Ferumoxytol Investigator's Drug Brochure, 2005); patients with significant drug or other allergies or autoimmune diseases may be enrolled at the Investigator's discretion Patients with clinically significant signs of uncal herniation, such as acute pupillary enlargement, rapidly developing motor changes (over hours), or rapidly decreasing level of consciousness, are not eligible Patients who require monitored anesthesia for MRI scanning Patients with history of hemochromatosis or iron overload Patients with renal insufficiency (glomerular filtration rate (GFR) < 50) Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ferumoxytol Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ferumoxytol<br>Patients receive ferumoxytol non-stoichiometric magnetite IV on day 2 then undergo DSC MRI, and DCE MRI, DWI (day 1 only), and TOF MR angiography on days 1-3 at 4 time points: before radiation, 3 weeks after initiation of radiation plus temozolomide, at the end of radiation (6 weeks post first dose) and 6 weeks after radiation (12 weeks post first dose). Ferumoxytol non-stoichiometric magnetite administration continues in the absence of unacceptable toxicity. | Drug: Ferumoxytol Non-Stoichiometric Magnetite<br>* Given IV<br>* Other names: Ferumoxytol;Other: Dynamic Contrast-Enhanced Magnetic Resonance Imaging<br>* Undergo DCE MRI<br>* Other names: DCE-MRI;Other: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging<br>* Undergo DSC MRI<br>* Other names: Dynamic Susceptibility Contrast-Enhanced MRI;Other: Diffusion Weighted Imaging<br>* Undergo DWI<br>* Other names: DWI-MRI;Other: MRI-Based Angiogram<br>* Undergo TOF MR angiography<br>* Other names: MRA;|
| Active Comparator: Gadoteridol<br>Patients receive gadoteridol IV on day 1 then undergo DSC MRI, and DCE MRI, DWI (day 1 only), and TOF MR angiography on days 1-3 at 4 time points: before radiation, 3 weeks after initiation of radiation plus temozolomide, at the end of radiation (6 weeks post first dose) and 6 weeks after radiation (12 weeks post first dose). | Drug: Gadolinium<br>* Given IV<br>* Other names: Gd;Other: Dynamic Contrast-Enhanced Magnetic Resonance Imaging<br>* Undergo DCE MRI<br>* Other names: DCE-MRI;Other: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging<br>* Undergo DSC MRI<br>* Other names: Dynamic Susceptibility Contrast-Enhanced MRI;Other: Diffusion Weighted Imaging<br>* Undergo DWI<br>* Other names: DWI-MRI;Other: MRI-Based Angiogram<br>* Undergo TOF MR angiography<br>* Other names: MRA;|
| Active Comparator: Gadoteridol Leakage Corrected<br>Patients receive gadoteridol IV on day 1 then undergo DSC MRI, and DCE MRI, DWI (day 1 only), and TOF MR angiography on days 1-3 at 4 time points: before radiation, 3 weeks after initiation of radiation plus temozolomide, at the end of radiation (6 weeks post first dose) and 6 weeks after radiation (12 weeks post first dose). | Drug: Gadolinium<br>* Given IV<br>* Other names: Gd;Other: Dynamic Contrast-Enhanced Magnetic Resonance Imaging<br>* Undergo DCE MRI<br>* Other names: DCE-MRI;Other: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging<br>* Undergo DSC MRI<br>* Other names: Dynamic Susceptibility Contrast-Enhanced MRI;Other: Diffusion Weighted Imaging<br>* Undergo DWI<br>* Other names: DWI-MRI;Other: MRI-Based Angiogram<br>* Undergo TOF MR angiography<br>* Other names: MRA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Cerebral Blood Volume (CBV) | Radiographical progression is determined based on RANO criteria. | At radiographical progression (between 6 and 12 weeks post first dose of chemoradiation) | 
| Tumor Progression on Conventional MR | Tumor progression was assessed by RANO criteria (Wen, 2010). | Anytime between baseline and 12 weeks post treatment initiation: average 6 weeks post treatment initiation. |