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

Overview

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.

Full Title of Study: “MR Imaging of Inflammatory Responses in the Central Nervous System With Ferumoxytol-Enhanced MRI (Pediatric Brain Tumor Protocol)”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Primary Purpose: Diagnostic
  • Masking: None (Open Label)
• Study Primary Completion Date: June 1, 2025

Detailed Description

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.

Interventions

• Diagnostic Test: Diagnostic (ferumoxytol-enhanced MRI)
  • Undergo ferumoxytol-enhanced MRI
• Procedure: Surgery
  • Undergo surgical resection
• Drug: Ferumoxytol
  • Given IV
• Other: Tissue Analysis
  • Correlative analysis for macrophage detection and quantification. This applies for all patients in the experimental arm who undergo ferumoxytol infusion.

Arms, Groups and Cohorts

• Experimental: Diagnostic (ferumoxytol-enhanced MRI)
  • 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.

Clinical Trial Outcome Measures

Primary Measures

• Iron concentration measurements
  • Time Frame: Day 1
  • Obtain susceptibility measurements and relaxation times (R2, R2*, R2′) in patients receiving ferumoxytol.

Secondary Measures

• Macrophages on histopathology
  • Time Frame: Days 2-4
  • Determine the number of macrophages in tissue samples at histopathology.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 2 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Michael Iv
• Collaborator
  • National Cancer Institute (NCI)
• Provider of Information About this Clinical Study
  • Sponsor-Investigator: Michael Iv, Clinical Assistant Professor – Stanford University
• Overall Official(s)
  • Michael Iv, Principal Investigator, Stanford University