Monitoring Anti-angiogenic Therapy in Brain Tumors by Advanced MRI

This research study is an Imaging Study, in which investigators are examining if advanced
magnetic resonance imaging (MRI) and spectroscopy (MRS) are able to predict the outcome of
participants with a brain tumor (glioblastoma) treated with an anti-angiogenic treatment
called Avastin (Avastin is the trade name for bevacizumab).

MRI studies the tumor size and other physical aspects of a tumor and the MRS adds an
additional analysis that measures the chemical changes that a tumor undergoes. This study
aims to test whether addition of MRS to standard MRI testing will help better predict how a
tumor is responding to therapy.

The names of the study interventions involved in this study are:

- MRI/MRS

- Avastin Avastin works by interfering with the process of new blood vessel growth and is
thus an anti-angiogenic. Avastin is approved by the U.S. Food and Drug Administration
for use in Glioblastoma .

The participant's treating physician may complement the Avastin treatment with chemotherapy
including Temozolomide (TMZ) or Lomustine (CCNU). Both treatments are approved by the U.S.
Food and Drug Administration for use in Glioblastoma.

The purpose of this study is to predict treatment response to anti-angiogenic therapy in
brain tumor participant using advanced MRI and MRS.

MRI/MRS is an FDA-approved test that uses magnets to take pictures of the brain and lets us
"see inside" the body/brain without surgery.

Inclusion Criteria:

- Participants must have histologically confirmed glioblastoma and evidence of
recurrence. Patients with low-grade tumors who have progressed to glioblastoma are
eligible.

- Participants must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as ≥
10 mm.

- Patients must be anti-angiogenic therapy naïve.

- Age ≥18 years. We exclude children because the chances of recruiting children with
recurrent glioblastoma who will be treated with bevacizumab are small.

- ECOG performance status ≤2 (Karnofsky ≥60%)

- Life expectancy of greater than 10 weeks.

- creatinine within normal institutional limits OR

- creatinine clearance ≥30 mL/min/1.73 m2 for participants with creatinine levels
above institutional normal.

- Participants must be able to undergo MRI scan.

- Participants whose clinical care plan includes treatment with bevacizumab mono-therapy
(Group I) or bevacizumab (+ cytotoxic agents Temozolomide (TMZ) or Lomustine (CCNU).

- Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

- Participants who have already received anti-VEGF or investigational anti-angiogenic
therapy for glioblastoma.

- 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 the effects of MR imaging on the
fetus are unknown and gadolinium-based intravenous contrast material is not
recommended for use in pregnant patients

- HIV-positive participants on combination antiretroviral therapy are ineligible because
of the potential for pharmacokinetic interactions with bevacizumab, Temozolomide (TMZ)
or Lomustine (CCNU).

- Patients who are no suitable to undergo MRI or use gadolinium contrast due to:

- Claustrophobia

- Presence of metallic objects or implanted medical devices in body (i.e. cardiac
pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves
with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel
implants)

- Sickle cell disease

- Renal failure

- Reduced renal function, as determined by creatinine clearance < 30 mL/min based
on a serum creatinine level obtained within 28 days prior to registration