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

Primary Purpose

Adult Brain Glioblastoma

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Gadolinium

Ferumoxytol Non-Stoichiometric Magnetite

Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging

Diffusion Weighted Imaging

MRI-Based Angiogram

About this trial

This is an interventional diagnostic trial for Adult Brain Glioblastoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

OHSU Knight Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

Ferumoxytol

Gadoteridol

Gadoteridol Leakage Corrected

Arm Description

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.

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).

Outcomes

Primary Outcome Measures

Mean Cerebral Blood Volume (CBV)

Radiographical progression is determined based on RANO criteria.

Tumor Progression on Conventional MR

Tumor progression was assessed by RANO criteria (Wen, 2010).

Secondary Outcome Measures

Full Information

NCT ID

NCT00660543

First Posted

April 10, 2008

Last Updated

April 19, 2017

Sponsor

OHSU Knight Cancer Institute

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00660543

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2017

Overall Recruitment Status

Completed

Study Start Date

December 2006 (undefined)

Primary Completion Date

June 2014 (Actual)

Study Completion Date

June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

OHSU Knight Cancer Institute

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Adult Brain Glioblastoma

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ferumoxytol

Arm Type

Experimental

Arm Description

Arm Title

Gadoteridol

Arm Type

Active Comparator

Arm Description

Arm Title

Gadoteridol Leakage Corrected

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Gadolinium

Other Intervention Name(s)

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Ferumoxytol Non-Stoichiometric Magnetite

Other Intervention Name(s)

Fe3O4, Feraheme, Ferumoxytol

Intervention Description

Given IV

Intervention Type

Other

Intervention Name(s)

Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Other Intervention Name(s)

DCE MRI, DCE-MRI

Intervention Description

Undergo DCE MRI

Intervention Type

Other

Intervention Name(s)

Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging

Other Intervention Name(s)

DSC-MRI, Dynamic Susceptibility Contrast-Enhanced MRI

Intervention Description

Undergo DSC MRI

Intervention Type

Other

Intervention Name(s)

Diffusion Weighted Imaging

Other Intervention Name(s)

Diffusion Weighted MRI, DWI, DWI MRI, DWI-MRI

Intervention Description

Undergo DWI

Intervention Type

Other

Intervention Name(s)

MRI-Based Angiogram

Other Intervention Name(s)

Magnetic Resonance Angiogram, MRA

Intervention Description

Undergo TOF MR angiography

Primary Outcome Measure Information:

Title

Mean Cerebral Blood Volume (CBV)

Description

Radiographical progression is determined based on RANO criteria.

Time Frame

At radiographical progression (between 6 and 12 weeks post first dose of chemoradiation)

Title

Tumor Progression on Conventional MR

Description

Tumor progression was assessed by RANO criteria (Wen, 2010).

Time Frame

Anytime between baseline and 12 weeks post treatment initiation: average 6 weeks post treatment initiation.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Edward Neuwelt

Organizational Affiliation

OHSU Knight Cancer Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

OHSU Knight Cancer Institute

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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