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

Adult Brain Glioblastoma Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00660543
• Other study ID #: 2753
• Secondary ID: NCI-2015-00224SO
• Status: Completed
• Phase: N/A
• First received: April 10, 2008
• Last updated: April 7, 2015
• Start date: December 2006
• Est. completion date: June 2014

Study information

• Verified date: April 2015
• Source: OHSU Knight Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Adult Brain Glioblastoma
• Glioblastoma

Intervention

Drug:
• Gadolinium
Given IV
• Ferumoxytol Non-Stoichiometric Magnetite
Given IV

Procedure:
• Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Undergo DCE MRI
• Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging
Undergo DSC MRI
• Diffusion Weighted Imaging
Undergo DWI
• MRI-Based Angiogram
Undergo TOF MR angiography

Locations

Country	Name	City	State
United States	OHSU Knight Cancer Institute	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
OHSU Knight Cancer Institute	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Up to 12 weeks post-treatment initiation	No
Primary	Changes in tumor vascular properties associated with standard radio/chemotherapy	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.	Baseline to up to 12 weeks post-treatment initiation	No
Secondary	Cerebral blood flow	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.	Up to 12 weeks post-treatment initiation	No
Secondary	Mean transit time	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.	Up to 12 weeks post-treatment initiation	No
Secondary	Time-to-peak	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.	Up to 12 weeks post-treatment initiation	No
Secondary	Qualitative assessment of tumor vascularity using TOF MR angiography	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.	Up to 12 weeks post-treatment initiation	No
Secondary	Changes in the apparent diffusion coefficient of tumor water associated with standard radio/chemotherapy measured using DWI	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.	Baseline to up to 12 weeks post-treatment initiation	No