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

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).

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

- Eastern Cooperative Oncology Group (ECOG) performance status > or = 2 (Karnofsky > or
=60%)

- Patients scheduled for standard therapy (6 weeks RT ~60 gray (Gy), 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 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.

- 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.