Ferumoxytol- and Gadolinium-Labeled MRI in Measuring Tumors Before or After Treatment in Patients With Primary or Metastatic Brain Tumors

PRIMARY OBJECTIVES:

I. To compare quantitative blood brain barrier permeability measurements (derived transfer
coefficient [Ktrans]) of a standard gadolinium (Gd) MRI contrast agent at 3T and 7T using
dynamic contrast enhancement (DCE) MRI.

II. To compare dynamic susceptibility contrast (DSC) based perfusion measures at 3T and 7T.

SECONDARY OBJECTIVES:

I. To describe the blood brain barrier permeability to ferumoxytol (ferumoxytol
non-stoichiometric magnetite) and to a standard gadolinium-based MRI contrast agent using
signal intensity changes as described above.

II. To describe cerebral blood volume (CBV) measurements obtained using a standard gadolinium
MRI contrast agent and ferumoxytol.

III. To evaluate tumor microvascularity on susceptibility-weighted images (SWI).

IV. To describe the microscopic distribution of ferumoxytol particles in tissue removed from
subjects undergoing surgery.

OUTLINE: Patients are assigned to 3T or 7T magnet within the subgroups.

Patients receive gadolinium intravenously (IV) on day 1 and ferumoxytol non-stoichiometric
magnetite IV on day 2. Patients undergo anatomical MRI sequences with 3T or 7T at baseline
and on days 1-3. Patients also undergo DSC MRI and DCE MRI on days 1-2. Day 1 and day 2
imaging sessions may be separated by up to 7 days.

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

Inclusion Criteria:

- Subjects with radiographically suspected, histologically or cytologically confirmed
primary brain tumors or brain metastasis are eligible

- Subjects may be enrolled at any point in diagnosis or treatment

- Subjects must have had radiographically evaluable or measurable disease with standard
magnetic resonance (MR) imaging

- Members of all races and ethnic groups will be included

- Eastern Cooperative Oncology Group (ECOG) performance status =< 3 (Karnofsky
performance status [KPS] >= 30)

- Ability to understand and the willingness to sign a written informed consent document,
or have a representative able to consent for the subject

- 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

- Subject agrees to complete follow up visit

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

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

- Subjects with known hepatic insufficiency or cirrhosis

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to ferumoxytol

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

- Subjects expecting to undergo surgery between the imaging sessions; subjects may
undergo surgery at any time before the first, or after the last imaging session; this
exclusion only applies to each study visit (3 day scanning session), and does not
apply to the time (at least 3 weeks) between each study visit

- Uncontrolled concurrent 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 or lactating women are excluded from this study

- Inability or unwillingness to undergo the complete series of imaging sessions;
inability or unwillingness to complete the one month follow-up

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

- Subjects with glomerular filtration rate (GFR) < 50

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