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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
  Purpose
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.

Condition Intervention
Adult Brain Glioblastoma
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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Early Assessment of Tumor Response to Therapy Using Ferumoxytol (Code 7228) as an MR Contrast Agent in Patients With Glioblastoma Multiforme (MedDRA Code 10018337)

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • 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).


Enrollment: 14
Study Start Date: December 2006
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • 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
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 Name: 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:
  • Diffusion Weighted MRI
  • DWI
  • DWI MRI
  • DWI-MRI
Other: MRI-Based Angiogram
Undergo TOF MR angiography
Other Names:
  • Magnetic Resonance Angiogram
  • MRA
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 Name: 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:
  • Diffusion Weighted MRI
  • DWI
  • DWI MRI
  • DWI-MRI
Other: MRI-Based Angiogram
Undergo TOF MR angiography
Other Names:
  • Magnetic Resonance Angiogram
  • MRA

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00660543

Locations
United States, Oregon
OHSU Knight Cancer Institute
Portland, Oregon, United States, 97239
Sponsors and Collaborators
OHSU Knight Cancer Institute
National Cancer Institute (NCI)
Investigators
Principal Investigator: Edward Neuwelt OHSU Knight Cancer Institute
  More Information

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT00660543     History of Changes
Other Study ID Numbers: 2753  NCI-2015-00224  SOL-06062-LX  813  NCI-2015-00204  8097  2753  P30CA069533 
Study First Received: April 10, 2008
Results First Received: February 12, 2016
Last Updated: April 8, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Ferrosoferric Oxide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Hematinics
Parenteral Nutrition Solutions
Pharmaceutical Solutions

ClinicalTrials.gov processed this record on December 02, 2016