Steady State Blood Volume Maps Using Ferumoxytol Non-stoichiometric Magnetite MRI in Imaging Patients With Glioblastoma

PRIMARY OBJECTIVES:

I. Testing if steady state (SS)-cerebral blood volume (CBV) maps are superior to dynamic
susceptibility contrast-(DSC)-CBV maps in visualizing of brain tumor blood volumes.

SECONDARY OBJECTIVES:

I. Development of the SS-CBV mapping for quantitative CBV estimation. II. Assessment of
therapeutic response. III. Association with survival. IV. Correlation of relative cerebral
blood volume (rCBV) with histology. V. Assessment of late ferumoxytol (ferumoxytol
non-stoichiometric magnetite) enhancement at various stages of disease.

OUTLINE:

Patients receive 2 doses (2nd dose optional) of gadoteridol intravenously (IV) and undergo
MRI including DSC or dynamic contrast enhanced imaging (DCE)-CBV mapping over approximately
45-60 minutes on day 1. Within 3 days, patients receive 3 doses of ferumoxytol
non-stoichiometric magnetite IV and undergo MRI including DSC and SS-CBV mapping after each
dose over approximately 90 minutes. Patients undergo MRI without contrast 24 hours after
ferumoxytol non-stoichiometric magnetite over approximately 30 minutes. This 3 day series of
imaging repeats at different stages of disease and may be performed up to 5 times: prior to
surgery, prior to chemoradiation therapy, 4-6 weeks post-chemoradiation therapy, at time of
progression on gadolinium MRI per Response Assessment in Neuro-Oncology (RANO) criteria, and
again at time of progression (if the previous time of progression showed pseudoprogression).

After completion of study, patients are followed up at 2 and 6 weeks.

Inclusion Criteria:

- Subjects must have a known or presumed radiological diagnosis of glioblastoma (GBM);
for presumed diagnosis of GBM, histological confirmation of GBM must be completed
within 12 weeks of enrollment; (subjects will be removed from study and non-evaluable
if no histologic diagnosis of GBM is confirmed)

- Subjects must be enrolled before starting chemoradiation, either pre -or post-surgery

- All subjects, or their legal guardians, must sign a written informed consent and
Health Insurance Portability and Accountability Act (HIPAA) authorization in
accordance with institutional guidelines

- Sexually active women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; surgical intervention i.e.
tubal ligation or vasectomy; post-menopausal > 6 months or abstinence) for at least
two months after each cycle of the study; should a female become pregnant or suspect
she is pregnant while participating in this study, she should inform her treating
physician immediately

Exclusion Criteria:

- Subjects 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

- Subjects with known allergic or hypersensitivity reactions to parenteral iron,
parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide
preparations; subjects with significant drug or other allergies or autoimmune diseases
may be enrolled at the investigator?s discretion

- Subjects who are pregnant or lactating or who suspect they might be pregnant

- Subjects who have a contraindication for 3 tesla (T) MRI: metal in their bodies (a
cardiac pacemaker or other incompatible device), are severely agitated, or have an
allergy to gadolinium containing contrast material

- Subjects with known iron overload (genetic hemochromatosis); in subjects with a family
history of hemochromatosis, hemochromatosis must be ruled out prior to study entry
with normal values of the following blood tests: transferrin saturation (TS) test and
serum ferritin (SF) test; all associated costs will be paid by the study

- Subject who have received ferumoxytol within 3 weeks of study entry

- Subjects with three or more drug allergies from separate drug classes