Magnetic Resonance (MR) Imaging Study Using Ferumoxytol to Assess Early Tumor Response in Patients With Glioblastoma Multiforme - Full Text View

Sponsors and Collaborators:	Oregon Health and Science University National Cancer Institute (NCI)
Information provided by:	Oregon Health and Science University
ClinicalTrials.gov Identifier:	NCT00660543

Purpose

In this study the investigators would like to find out how a new iron containing Magnetic Resonance Imaging (MRI) contrast agent, called "ferumoxytol" can help the investigators to assess at the beginning of a therapy if it is effective or not in the treatment of a brain tumor called Glioblastoma Multiforme (GBM). For this purpose, after intravenous ferumoxytol injection, special MR scans (called: dynamic perfusion, blood-brain barrier (BBB) permeability measurement) will be performed to see the vascular changes in the brain and tumor.

Condition	Intervention	Phase
Diagnostic Imaging	Drug: Ferumoxytol	Phase I

MedlinePlus related topics: Cancer

Drug Information available for: Temozolomide Sodium chloride Ferumoxytol

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Diagnostic, Open Label, Single Group Assignment
Official Title:	Early Assessment of Tumor Response to Therapy Using Ferumoxytol (Code 7228) as an MR Contrast Agent in Patients With Glioblastoma Multiforme

Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	12
Study Start Date:	October 2006
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Patients will be scanned at four time-points of their radiation/temozolomide treatment: before onset of radiation/temozolomide treatment, at 3 weeks, 6 weeks and 12 weeks following the onset of treatment. Each time-point will consist of three visits on three consecutive days. On first day: MRI with and without gadolinium (the usual MR contrast agent) infusion (0.1 mmol/kg). On second day: MRI with ferumoxytol infusion (1 mg/kg). On the third day: MRI without additional contrast agent, 24 hr post ferumoxytol infusion. There will be follow up visits 1 month and 6 months after the last ferumoxytol injection	Drug: Ferumoxytol The ferumoxytol will be injected as an IV bolus of 2 mg Fe/kg over approximately 2-4 seconds at 4 ml/s flow rate, followed by a saline flush, at four time points: 2 mg/kg before, after 3 weeks of the 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). Cumulative ferumoxytol dose is 8 mg/kg about the half of the iron therapy dose (2 x 510 mg).

Arms

Assigned Interventions

1: Experimental

Patients will be scanned at four time-points of their radiation/temozolomide treatment: before onset of radiation/temozolomide treatment, at 3 weeks, 6 weeks and 12 weeks following the onset of treatment. Each time-point will consist of three visits on three consecutive days. On first day: MRI with and without gadolinium (the usual MR contrast agent) infusion (0.1 mmol/kg). On second day: MRI with ferumoxytol infusion (1 mg/kg). On the third day: MRI without additional contrast agent, 24 hr post ferumoxytol infusion. There will be follow up visits 1 month and 6 months after the last ferumoxytol injection

Drug: Ferumoxytol

The ferumoxytol will be injected as an IV bolus of 2 mg Fe/kg over approximately 2-4 seconds at 4 ml/s flow rate, followed by a saline flush, at four time points:

2 mg/kg before, after 3 weeks of the 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). Cumulative ferumoxytol dose is 8 mg/kg about the half of the iron therapy dose (2 x 510 mg).

Detailed Description:

Patients will be scanned at four time-points of their radiation/temozolomide treatment: before onset of radiation/temozolomide treatment, at 3 weeks, 6 weeks and 12 weeks following the onset of treatment. Each time-point will consist of three visits on three consecutive days. On first day: MRI with and without gadolinium (the usual MR contrast agent) infusion (0.1 mmol/kg). On second day: MRI with ferumoxytol infusion (1 mg/kg). On the third day: MRI without additional contrast agent, 24 hr post ferumoxytol infusion. There will be follow up visits 1 month and 6 months after the last ferumoxytol injection.

The ferumoxytol molecule contains iron-oxide and other components (carbohydrate), which makes ferumoxytol safe for short and fast (bolus) injections. This new contrast agent has not shown significant side effects, even using extremely high doses in animal experiments. A total of 516 human subjects have received one or more doses of ferumoxytol. There have been 3 cases with serious side effects possibly related to the administration of ferumoxytol. Two cases of peritonitis (the inflammation of the lining the abdomen) that were possibly related and one case of anaphylaxis (serious allergic reaction) related to ferumoxytol. (Of note is that gadolinium, the standard contrast agent, carries a serious risk for persons with kidney dysfunction. This risk is the condition called nephrogenic systemic fibrosis (NSF), which causes scar tissue to develop and can, in some cases, affect internal organs and even lead to death.)

The various types of MR measurement (Perfusion, blood-brain barrier permeability, diffusion) will be evaluated or measured at each time-point, for each contrast agent. Certain regions will be described and the data will be evaluated throughout the study in an attempt to correlate changes with tumor response to therapy. The tumor volume will be evaluated by 2 radiologists, measuring the diameters of the largest areas of contrast enhancement and signal intensities will be also compared (semi-quantitatively).

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
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.
Patients have not had prior chemotherapy and/or radiotherapy
Life expectancy of greater than 6 months
ECOG performance status > or = 2 (Karnofsky > or =60%)
Patients scheduled for standard therapy (6 weeks RT ~60Gy, plus temozolomide 75 mg/m2 during 6w RT, 200 mg/m2 5x wk post RT started 4wk after RT)
Patients must be on a stable dose (up to 8mg 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.
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 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.
Patients who require monitored anesthesia for MRI scanning
Patient with history of hemochromatosis or iron overload
Patients with stage IV or V renal insufficiency
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. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ferumoxytol, breastfeeding should be discontinued if the mother is treated with ferumoxytol
HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ferumoxytol.

Contacts and Locations

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

Contacts

Contact: Edward A Neuwelt, MD	503-494-5626	neuwelte@ohsu.edu
Contact: Nancy A Hedrick, BA	503-494-5626	hedrickn@ohsu.edu

Locations

United States, Oregon
Oregon Health & Science University	Recruiting
Portland, Oregon, United States, 97239
Contact: Edward A Neuwelt, MD 503-494-5626 neuwelte@ohsu.edu
Principal Investigator: Edward A Neuwelt, MD

Sponsors and Collaborators

Oregon Health and Science University

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Edward A Neuwelt, MD

Oregon Health and Science University

More Information

Responsible Party:	Oregon Health & Science University ( Edward A. Neuwelt, MD )
Study ID Numbers:	OHSU-2753, NCI 26XS293
Study First Received:	April 10, 2008
Last Updated:	October 3, 2008
ClinicalTrials.gov Identifier:	NCT00660543
Health Authority:	United States: Food and Drug Administration

Keywords provided by Oregon Health and Science University:

ferumoxytol

Study placed in the following topic categories:

Neuroectodermal Tumors
Glioblastoma
Glioblastoma multiforme
Astrocytoma
Neoplasms, Germ Cell and Embryonal

Neuroepithelioma
Glioma
Temozolomide
Iron
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial

ClinicalTrials.gov processed this record on January 15, 2009