In Vivo Characterization of Macrophages in Pediatric Patients With Malignant Brain Tumors Using Ferumoxytol-enhanced MRI

Study Overview
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Brief Summary
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This pilot early phase I trial studies how well ferumoxytol-enhanced magnetic resonance imaging (MRI) correlates with inflammatory (macrophage) responses in pediatric patients with malignant brain tumors. If there is good correlation, ferumoxytol-enhanced MRI can serve as a noninvasive imaging biomarker of inflammation.

Detailed Description
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PRIMARY OBJECTIVE: I. To establish the magnetic resonance (MR) imaging signal characteristics of macrophages in pediatric patients (>= 2 years old) with newly diagnosed malignant brain tumors using ferumoxytol, an ultrasmall superparamagnetic iron oxide (USPIO) particle. SECONDARY OBJECTIVES: I. To correlate the MRI signal of ferumoxytol uptake in macrophages with the number of macrophages in surgical tumor specimen at histopathology. OUTLINE: Patients receive a single intravenous infusion of ferumoxytol over 15 minutes. After 24 hours, patients undergo ferumoxytol-enhanced magnetic resonance imaging (MRI). Patients will then undergo MRI-localized tissue sampling and tumor resection.

Official Title
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MR Imaging of Inflammatory Responses in the Central Nervous System With Ferumoxytol-Enhanced MRI (Pediatric Brain Tumor Protocol)

Conditions
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Childhood Brain Neoplasm

Intervention / Treatment
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* Diagnostic Test: Diagnostic (ferumoxytol-enhanced MRI)
* Procedure: Surgery
* Drug: Ferumoxytol
* Other: Tissue Analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any patient with suspected malignant brain tumor on diagnostic MR imaging who will undergo a resection Exclusion Criteria: Informed consent cannot be obtained either from the patient or legal representative Severe coexisting or terminal systemic disease that may interfere with the conduct of the study Contraindication to MRI (metal implants) Hemosiderosis/hemochromatosis Iron overload from any cause (not just hemosiderosis or hemochromatosis), even if secondary to frequent blood transfusions, severe chronic hemolysis, excess dietary or parenteral iron, or any other etiology Known hypersensitivity to ferumoxytol or any of its components Pregnant patients

Ages Eligible for Study
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Minimum Age: 2 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (ferumoxytol-enhanced MRI)<br>All subjects in the experimental arm will have a single intravenous dose of ferumoxytol (5 mg Fe/kg), to be administered 24 hours before the subject undergoes ferumoxytol-enhanced magnetic resonance imaging (MRI). These subjects will subsequently undergo surgery, and tissue analysis of surgically resected samples (specifically the number of iron-containing and non-iron-containing macrophages) will be correlated with imaging features on ferumoxytol-enhanced MRI. | Diagnostic Test: Diagnostic (ferumoxytol-enhanced MRI)<br>* Undergo ferumoxytol-enhanced MRI<br>* Other names: Contrast-enhanced MRI;Procedure: Surgery<br>* Undergo surgical resection<br>Drug: Ferumoxytol<br>* Given IV<br>* Other names: FERUMOXYTOL NON-STOICHIOMETRIC MAGNETITE;Other: Tissue Analysis<br>* Correlative analysis for macrophage detection and quantification. This applies for all patients in the experimental arm who undergo ferumoxytol infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Iron concentration measurements | Obtain susceptibility measurements and relaxation times (R2, R2*, R2') in patients receiving ferumoxytol. | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Macrophages on histopathology | Determine the number of macrophages in tissue samples at histopathology. | Days 2-4 |