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:
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT00660543
First received: April 10, 2008
Last updated: April 7, 2015
Last verified: April 2015
  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
Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Procedure: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging
Procedure: Diffusion Weighted Imaging
Procedure: MRI-Based Angiogram

Study Type: Interventional
Study Design: 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:
  • Tumor vascular properties with specific emphasis on cerebral blood volume (CBV) and quantitative measurement of blood brain barrier (BBB) permeability (Ktrans) assessed using contrast enhanced MRI techniques [ Time Frame: Up to 12 weeks post-treatment initiation ] [ Designated as safety issue: No ]
    CBV will be quantified using DSC techniques using both gadolinium and ferumoxytol contrast agents. CBV values obtained with both contrast agents will be compared. BBB permeability will be quantified using DCE techniques for both contrast agents. The association of delayed ferumoxytol enhancement compared to early gadolinium enhancement will be investigated using regression techniques. These estimates assume paired, normally-distributed data using a one-sample t-test.

  • Changes in tumor vascular properties associated with standard radio/chemotherapy [ Time Frame: Baseline to up to 12 weeks post-treatment initiation ] [ Designated as safety issue: No ]
    Tumor CBV will be measured and compared before, during, and after therapy. Gadolinium and ferumoxytol BBB permeability will be measured and compared before, during, and after therapy. Differences that may be detected with a sample size of 15 patients are estimated for two outcome measures; relative CBV and Ktrans.


Secondary Outcome Measures:
  • Cerebral blood flow [ Time Frame: Up to 12 weeks post-treatment initiation ] [ Designated as safety issue: No ]
    Gadolinium and ferumoxytol contrast agents will be compared for assessing CBF perfusion parameters, and evaluate if any of these perfusion parameters is promising for tracking GBM therapeutic response. Exploratory analyses will be performed. Data from these analyses will be used to determine which outcomes have smallest coefficient of variation in comparison to clinically meaningful differences.

  • Mean transit time [ Time Frame: Up to 12 weeks post-treatment initiation ] [ Designated as safety issue: No ]
    Gadolinium and ferumoxytol contrast agents will be compared for assessing MTT perfusion parameters, and evaluate if any of these perfusion parameters is promising for tracking GBM therapeutic response. Exploratory analyses will be performed. Data from these analyses will be used to determine which outcomes have smallest coefficient of variation in comparison to clinically meaningful differences.

  • Time-to-peak [ Time Frame: Up to 12 weeks post-treatment initiation ] [ Designated as safety issue: No ]
    Gadolinium and ferumoxytol contrast agents will be compared for assessing TTP perfusion parameters, and evaluate if any of these perfusion parameters is promising for tracking GBM therapeutic response. Exploratory analyses will be performed. Data from these analyses will be used to determine which outcomes have smallest coefficient of variation in comparison to clinically meaningful differences.

  • Qualitative assessment of tumor vascularity using TOF MR angiography [ Time Frame: Up to 12 weeks post-treatment initiation ] [ Designated as safety issue: No ]
    Exploratory analyses will be performed. Data from these analyses will be used to determine which outcomes have smallest coefficient of variation in comparison to clinically meaningful differences.

  • Changes in the apparent diffusion coefficient of tumor water associated with standard radio/chemotherapy measured using DWI [ Time Frame: Baseline to up to 12 weeks post-treatment initiation ] [ Designated as safety issue: No ]
    ADC will be calculated from data acquired before, during, and after therapy. The utility of ADC measurements will be evaluated as a predictor of therapeutic response. Exploratory analyses will be performed. Data from these analyses will be used to determine which outcomes have smallest coefficient of variation in comparison to clinically meaningful differences.


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: Diagnostic (gadolinium, ferumoxytol, MRI sequences)
Patients receive gadolinium IV on day 1 and 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. Patients also receive temozolomide and undergo radiation therapy per standard of care.
Drug: Gadolinium
Given IV
Other Name: Gd
Drug: Ferumoxytol Non-Stoichiometric Magnetite
Given IV
Other Names:
  • Fe3O4
  • Feraheme
  • Ferumoxytol
Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Undergo DCE MRI
Other Names:
  • DCE MRI
  • DCE-MRI
Procedure: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging
Undergo DSC MRI
Other Names:
  • DSC-MRI
  • Dynamic Susceptibility Contrast-Enhanced MRI
Procedure: Diffusion Weighted Imaging
Undergo DWI
Other Names:
  • Diffusion Weighted Imaging
  • Diffusion Weighted MRI
  • DWI
  • DWI MRI
  • DWI-MRI
Procedure: 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
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
Investigators
Principal Investigator: Edward Neuwelt OHSU Knight Cancer Institute
  More Information

No publications provided

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
Last Updated: April 7, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Contrast Media
Ferrosoferric Oxide
Diagnostic Uses of Chemicals
Hematinics
Hematologic Agents
Parenteral Nutrition Solutions
Pharmaceutical Solutions
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2015