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

Imaging Vascular Properties of Pediatric Brain Tumors Using DSC-MRI With Ferumoxytol (Code 7228) and DCE-MRI With Gadolinium in a Single Imaging Session: An NCI Sponsored Exploratory Trial

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.

Study Overview

• Status: Completed
• Conditions: Childhood Brain Neoplasm; Recurrent Childhood Brain Neoplasm
• Intervention / Treatment: Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Drug: Gadolinium; Procedure: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging; Drug: Ferumoxytol Non-Stoichiometric Magnetite

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Knight Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Diagnostic (DSC-MRI with ferumoxytol, DCE-MRI with 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.

Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Undergo DCE-MRI; Other Names: DCE-MRI; DCE MRI; DYNAMIC CONTRAST ENHANCED MRI; Drug: Gadolinium; Given IV; Other Names: Gd; Procedure: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging; Undergo DSC-MRI; Other Names: Dynamic Susceptibility Contrast-Enhanced MRI; Drug: Ferumoxytol Non-Stoichiometric Magnetite; Given IV; Other Names: Feraheme; Ferumoxytol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vascular Properties of Pediatric Brain Tumors Using Dynamic Susceptibility-weighted Contrast Enhanced MRI (DSC-MRI) After Administration of Ferumoxytol	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).	Up to 2 years
Vascular Properties of Pediatric Brain Tumors Using Dynamic Contrast-enhanced MRI (DCE-MRI) After Administration of a Gadolinium-based Contrast Agent	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.	up to 2 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: OHSU Knight Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Edward Neuwelt, OHSU Knight Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2009
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: September 16, 2009
• First Submitted That Met QC Criteria: September 16, 2009
• First Posted (Estimate): September 17, 2009

Study Record Updates

• Last Update Posted (Actual): August 3, 2022
• Last Update Submitted That Met QC Criteria: July 11, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms; Brain Neoplasms; Hematinics; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Ferrosoferric Oxide
• Other Study ID Numbers: IRB00005405; R01CA137488 (U.S. NIH Grant/Contract); 813; 5405 (OHSU Knight Cancer Institute); NCI-2015-00227 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 1562; 2864; SOL-09064-LX