DSC-MRI With Ferumoxytol and DCE-MRI With Gadolinium in Imaging Vascular Properties in Younger Patients With Brain Tumors

Early Phase 1

Completed

Conditions: Recurrent Childhood Brain Neoplasm
Childhood Brain Neoplasm

Interventions: Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Procedure: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging
Drug: Ferumoxytol Non-Stoichiometric Magnetite
Drug: Gadolinium

Registration Number: NCT00978562

Lead Sponsor: OHSU Knight Cancer Institute

Brief Summary: This clinical trial studies dynamic susceptibility-weighted contrast enhanced magnetic resonance imaging (DSC-MRI) after administration of ferumoxytol and dynamic contrast-enhanced MRI (DCE-MRI) after administration of a gadolinium-based contrast agent (GBCA) in viewing the vessels of the brain in younger patients with brain tumors. Ferumoxytol is an experimental form of very small iron particles that are taken by the blood stream to cells adjacent and inside the tumor. These iron particles may make it easier to see the areas of the brain that are affected by tumor. Ferumoxytol may work better than standard GBCA in viewing the vessels of the brain and brain tumor on MRI. Using ferumoxytol and GBCA in the same MRI session may provide more information about tumor blood supply and the extent of the tumor.

Detailed Description: PRIMARY OBJECTIVES:

I. To describe the vascular properties of pediatric brain tumors using ferumoxytol for DSC-MRI and GBCA for DCE-MRI in pediatric brain tumor (proven or presumptive) patients in a single MRI session.

II. To describe evolving imaging characteristics of tumor vasculature using DSC-MRI with ferumoxytol and DCE-MRI with GBCA in pediatric brain tumor patients.

SECONDARY OBJECTIVES:

I. Compare and evaluate magnetic resonance angiogram (MRA) with ferumoxytol between different time points.

II. To describe number and size of tumors imaged. III. To assess histology and electron microscopy (EM) on tissue samples. IV. To demonstrate differences in patients with prior therapy versus (vs.) no prior therapy (radiation and/or chemotherapy).

OUTLINE:

Patients receive ferumoxytol and gadolinium intravenously (IV) and then undergo DSC-MRI and DCE-MRI. An optional MRI without injection of a contrast agent may be obtained after 20-24 hours at the discretion of the clinician. Patients may receive up to 3 more scans at least 3 weeks apart over up to 2 years.

After completion of study treatment, patients are followed up at approximately 4-6 weeks.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 14

Inclusion Criteria

Participant must have either radiological (presumptive) or established (proven) histological diagnosis of a brain tumor or lesion
Previously untreated participants must have a measureable lesion on an imaging study
Participants undergoing active treatment, or who have completed treatment, will have radiographic abnormalities that may or may not be recurrent tumor
Those participants requiring surgical intervention for diagnostic and/or therapeutic purposes as necessary for their disease are eligible; the tissue may be assessed by histology and/or EM for iron particles; only clinically indicated biopsy and/or surgery will be done
Participants may have had prior therapy for the primary brain tumor, including surgery, radiotherapy or chemotherapy
After entry into the study, participants agree to be followed for up to 6 weeks after the final infusion of ferumoxytol
All participants, or their legal guardians, must sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization in accordance with institutional guidelines
Baseline MRI studies for participants receiving ferumoxytol must be performed within 16 weeks of study entry
Sexually active women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study treatment and for the duration of study treatment; should a female become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Exclusion Criteria

Participants 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
Participants with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations, are not eligible; participants with significant drug or other allergies or autoimmune diseases may be enrolled at the Investigator's discretion
Participants who are pregnant, lactating, or who suspect they might be pregnant are not eligible
Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than 2.5 x upper limits of normal
Glomerular filtration rate (GFR) < 50
Participants who have a contraindication for MRI: metal in their bodies (a cardiac pacemaker or other incompatible device), are severely agitated, or have an allergy to GBCA
Participants with known hepatic insufficiency or cirrhosis
Human immunodeficiency virus (HIV)-positive participants on combination antiretroviral therapy are ineligible
Participants that have a known or suspected iron overload (genetic hemochromatosis or history of multiple transfusions)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Diagnostic (DSC-MRI with ferumoxytol, DCE-MRI with gadolinium)	Dynamic Contrast-Enhanced Magnetic Resonance Imaging	Patients receive ferumoxytol and gadolinium IV and then undergo DSC-MRI and DCE-MRI. An optional MRI without injection of a contrast agent may be obtained after 20-24 hours at the discretion of the clinician. Patients may receive up to 3 more scans at least 3 weeks apart over up to 2 years.
Diagnostic (DSC-MRI with ferumoxytol, DCE-MRI with gadolinium)	Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging	Patients receive ferumoxytol and gadolinium IV and then undergo DSC-MRI and DCE-MRI. An optional MRI without injection of a contrast agent may be obtained after 20-24 hours at the discretion of the clinician. Patients may receive up to 3 more scans at least 3 weeks apart over up to 2 years.
Diagnostic (DSC-MRI with ferumoxytol, DCE-MRI with gadolinium)	Gadolinium	Patients receive ferumoxytol and gadolinium IV and then undergo DSC-MRI and DCE-MRI. An optional MRI without injection of a contrast agent may be obtained after 20-24 hours at the discretion of the clinician. Patients may receive up to 3 more scans at least 3 weeks apart over up to 2 years.
Diagnostic (DSC-MRI with ferumoxytol, DCE-MRI with gadolinium)	Ferumoxytol Non-Stoichiometric Magnetite	Patients receive ferumoxytol and gadolinium IV and then undergo DSC-MRI and DCE-MRI. An optional MRI without injection of a contrast agent may be obtained after 20-24 hours at the discretion of the clinician. Patients may receive up to 3 more scans at least 3 weeks apart over up to 2 years.

Primary Outcome Measures

Name	Time	Method
Vascular Properties of Pediatric Brain Tumors Using Dynamic Susceptibility-weighted Contrast Enhanced MRI (DSC-MRI) After Administration of Ferumoxytol	Up to 2 years	Signal intensity, relative cerebral blood volume (rCBV) was measured. Relative CBV measurements were calculated from regions of interest (ROI) that were placed in regions of highest perfusion seen on the rCBV color overlay parametric maps.The mean of 3 regions of contralateral white matter was used as the internal reference standard. The size of the ROIs was kept constant (radius 1.5 mm). Parametric color overlay maps were analyzed using ImageJ software (NIH, Bethesda, MD, USA).
Vascular Properties of Pediatric Brain Tumors Using Dynamic Contrast-enhanced MRI (DCE-MRI) After Administration of a Gadolinium-based Contrast Agent	up to 2 years	Volume transfer coefficient reflecting vascular permeability of pediatric brain tumors using Dynamic Contrast-enhanced MRI (DCE-MRI) was measured. Subjects undergo MRI with ferumoxytol (study drug) and gadolinium (standard contrast agent) in the same imaging session. Ferumoxytol is given first and DSC images obtained, followed by gadolinium, and DCE images are obtained.

Secondary Outcome Measures

Name	Time	Method
Tumor Vascularity	Up to 2 years	Appropriate descriptive statistics will be estimated. Results will be posted at overall completion.
Ultrastructure (Only in Patients for Whom a Biopsy or Surgery is Scheduled Outside of This Protocol)	Up to 2 years	Appropriate descriptive statistics will be estimated. Results will be posted at overall completion.
Number of Enhancing Lesions	Up to 2 years	Appropriate descriptive statistics will be estimated. Results will be posted at overall completion.
Volume of Enhancing Lesions	Up to 2 years	Appropriate descriptive statistics will be estimated. Results will be posted at overall completion.
Histology (Only in Patients for Whom a Biopsy or Surgery is Scheduled Outside of This Protocol)	Up to 2 years	Appropriate descriptive statistics will be estimated. Results will be posted at overall completion.