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

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

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.

Study Overview

• Status: Completed
• Conditions: Adult Brain Glioblastoma
• Intervention / Treatment: 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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

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: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ferumoxytol; 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; Given IV; Other Names: Feraheme; Ferumoxytol; Fe3O4; Other: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Undergo DCE MRI; Other Names: DCE-MRI; DCE MRI; Other: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging; Undergo DSC MRI; Other Names: DSC-MRI; Dynamic Susceptibility Contrast-Enhanced MRI; Other: Diffusion Weighted Imaging; Undergo DWI; Other Names: DWI; Diffusion Weighted MRI; DWI MRI; DWI-MRI; Other: MRI-Based Angiogram; Undergo TOF MR angiography; Other Names: MRA; Magnetic Resonance Angiogram
Active Comparator: Gadoteridol; 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; Given IV; Other Names: Gd; Other: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Undergo DCE MRI; Other Names: DCE-MRI; DCE MRI; Other: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging; Undergo DSC MRI; Other Names: DSC-MRI; Dynamic Susceptibility Contrast-Enhanced MRI; Other: Diffusion Weighted Imaging; Undergo DWI; Other Names: DWI; Diffusion Weighted MRI; DWI MRI; DWI-MRI; Other: MRI-Based Angiogram; Undergo TOF MR angiography; Other Names: MRA; Magnetic Resonance Angiogram
Active Comparator: Gadoteridol Leakage Corrected; 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; Given IV; Other Names: Gd; Other: Dynamic Contrast-Enhanced Magnetic Resonance Imaging; Undergo DCE MRI; Other Names: DCE-MRI; DCE MRI; Other: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging; Undergo DSC MRI; Other Names: DSC-MRI; Dynamic Susceptibility Contrast-Enhanced MRI; Other: Diffusion Weighted Imaging; Undergo DWI; Other Names: DWI; Diffusion Weighted MRI; DWI MRI; DWI-MRI; Other: MRI-Based Angiogram; Undergo TOF MR angiography; Other Names: MRA; Magnetic Resonance Angiogram

What is the study measuring?

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.

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: December 1, 2006
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: April 10, 2008
• First Submitted That Met QC Criteria: April 11, 2008
• First Posted (Estimate): April 17, 2008

Study Record Updates

• Last Update Posted (Actual): May 16, 2017
• Last Update Submitted That Met QC Criteria: April 19, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Hematinics; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Ferrosoferric Oxide
• Other Study ID Numbers: IRB00002753; P30CA069533 (U.S. NIH Grant/Contract); 2753 (OHSU Knight Cancer Institute); 813; NCI-2015-00224 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); SOL-06062-LX; NCI-2015-00204; 8097