Ferumoxytol in Improving MR Imaging in Patients With High-Grade Brain Tumors or Cerebral Metastases

PRIMARY OBJECTIVES:

I. Investigate the utility of ferumoxytol and gadolinium-based contrast agent (GBCA) for
improved imaging biomarkers of malignant brain tumors in a single imaging session by
comparing dynamic susceptibility contrast (DSC) determined relative cerebral blood volume
(rCBV) and dynamic contrast enhancement (DCE) determined vascular permeability (derived
transfer coefficient [Ktrans]).

SECONDARY OBJECTIVES:

I. Compare and evaluate magnetic resonance angiography (MRA) with ferumoxytol between
different time points.

II. Assess number and size of tumors imaged. III. Assess tumor vascularity. IV. Assess
histology and electron microscopy (EM) on tissue samples. V. Assess differences in subjects
with prior therapy versus (vs.) no prior therapy (radiation and/or chemotherapy).

VI. Assess the long term imaging characteristics of different tumors using DSC and DCE.

OUTLINE:

Patients receive ferumoxytol non-stoichiometric magnetite intravenously (IV) beginning
approximately 15 seconds after start of 3T DSC-MRI and GBCA IV approximately 1 minute and 50
seconds after start of 3T DCE-MRI on day 1. Patients also undergo MRI without contrast at
baseline and on day 2. Imaging with ferumoxytol, GBCA, and without contrast repeats every 3
weeks for a total of 6 more imaging sessions over up to 5 years.

After completion of study, patients are followed up at approximately 4-6 weeks.

Inclusion Criteria:

- Subject must have either radiological or established histological diagnosis of the
following general categories:

- High-grade glioma/central nervous system (CNS) lymphoma or

- Brain metastases

- Previously untreated subjects must have a lesion on an imaging study

- Post treatment subjects will have radiographic abnormalities that may or may not be
recurrent tumor

- Subjects agree to be contacted 4-6 weeks after each study visit

- Subjects, or their legal guardian, 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; or abstinence) prior to
study treatment and for the duration of study treatment; should a female become
pregnant or suspect she is pregnant while participating in this study, she should
inform her treating physician immediately

- Pre-imaging radiological scans/studies must be performed approximately 16 weeks prior
to study entry; but not less than 24 hours prior

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 (Ferumoxytol Investigator's Drug Brochure, 2012); 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 require monitored anesthesia for MRI scanning

- Subjects with renal insufficiency; glomerular filtration rate (GFR) < 50

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

- Subjects with known hepatic insufficiency or cirrhosis

- Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral
therapy are ineligible

- Subjects with known or suspected iron overload (genetic hemochromatosis or history of
multiple transfusions)

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