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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT00660543
First received: April 10, 2008
Last updated: April 8, 2016
Last verified: April 2016

April 10, 2008
April 8, 2016
December 2006
June 2014   (final data collection date for primary outcome measure)
  • Mean Cerebral Blood Volume (CBV) [ Time Frame: At radiographical progression (between 6 and 12 weeks post first dose of chemoradiation) ] [ Designated as safety issue: No ]
    Radiographical progression is determined based on RANO criteria.
  • Tumor Progression on Conventional MR [ Time Frame: Anytime between baseline and 12 weeks post treatment initiation: average 6 weeks post treatment initiation. ] [ Designated as safety issue: No ]
    Tumor progression was assessed by RANO criteria (Wen, 2010).
To characterize GBM tumor vascular properties using Ferumoxytol and compare to those obtained using Gd based MRI contrast agent. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00660543 on ClinicalTrials.gov Archive Site
Not Provided
  • Comparison of Gd and Ferumoxytol contrast agents for assessing cerebral blood flow , mean transit time , and time-to-peak perfusion parameters, and evaluate if any of these perfusion parameters is promising for tracking GBM therapeutic response. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • To obtain qualitative assessment of tumor vascularity using time-of-flight(TOF) MR angiography techniques. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • To characterize changes in the apparent diffusion coefficient (ADC) of tumor water associated with standard radio/chemotherapy in GBM. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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.

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.

Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Adult Brain Glioblastoma
  • Drug: Gadolinium
    Given IV
    Other Name: Gd
  • Drug: Ferumoxytol Non-Stoichiometric Magnetite
    Given IV
    Other Names:
    • Fe3O4
    • Feraheme
    • Ferumoxytol
  • 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:
    • Diffusion Weighted MRI
    • DWI
    • DWI MRI
    • DWI-MRI
  • Other: MRI-Based Angiogram
    Undergo TOF MR angiography
    Other Names:
    • Magnetic Resonance Angiogram
    • MRA
  • 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.
    Interventions:
    • 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
  • 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).
    Interventions:
    • Drug: Gadolinium
    • Other: Dynamic Contrast-Enhanced Magnetic Resonance Imaging
    • Other: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging
    • Other: Diffusion Weighted Imaging
    • Other: MRI-Based 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).
    Interventions:
    • Drug: Gadolinium
    • Other: Dynamic Contrast-Enhanced Magnetic Resonance Imaging
    • Other: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging
    • Other: Diffusion Weighted Imaging
    • Other: MRI-Based Angiogram
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
14
June 2014
June 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00660543
2753, NCI-2015-00224, SOL-06062-LX, 813, NCI-2015-00204, 8097, 2753, P30CA069533
Yes
Not Provided
Not Provided
OHSU Knight Cancer Institute
OHSU Knight Cancer Institute
National Cancer Institute (NCI)
Principal Investigator: Edward Neuwelt OHSU Knight Cancer Institute
OHSU Knight Cancer Institute
April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP