Inclusion Criteria:

1. Patients must be at least 18 years of age

2. Patients must have a Karnofsky performance status > 60% (i.e. the patient must be
able to care for himself/herself with occasional help from others)

3. Patients must have the following hematologic, renal and liver function (i.e. Absolute
neutrophil count > 1500/mm3, Platelets > 100,000/mm3, creatinine < 1.7 mg/dl, total
bilirubin ≤ 1.5 mg/dl, transaminases < 4 times above the upper limits of the
institutional normal

4. Patients must be able to provide written informed consent

5. Patients with the potential for pregnancy or impregnating their partner must agree to
follow acceptable birth control methods to avoid conception. Women of childbearing
potential must have a negative pregnancy test. The anti-proliferative activity of
this experimental drug as well as the standard drug (temozolomide) may be harmful to
the developing fetus or nursing infant

6. Patients must have a Mini Mental Status Exam score of > 15

7. Patients must have tumor tissue form completed and signed by a pathologist. See
section 9.6 for details

Phase I Criteria (Phase I Patients ONLY)

1. Patients must have histologically proven supratentorial malignant glioma (anaplastic
astrocytoma, anaplastic oligodendroglioma or glioblastoma multiforme)

2. Patients must have received at least 80% of planned temozolomide and radiation
therapy with no grade 3 or grade 4 toxicity attributed to the temozolomide

3. Patients must have received planned treatment with radiation therapy and concomitant
temozolomide at least 28 days but no more than 49 days prior to starting treatment on
this study

4. Patients must have Gadolinium MRI or contrast CT scan within 28 days of starting
treatment

Exclusion Criteria:

1. Patients with serious concurrent infection or medical illness, which would jeopardize
the ability of the patient to receive the treatment outlined in this protocol with
reasonable safety

2. Patients who are pregnant or breast-feeding. The anti-proliferative activity of this
experimental drug and temozolomide may be harmful to the developing fetus or nursing
infant

3. Patients receiving concurrent therapy for their tumor (i.e. chemotherapeutics or
investigational agents)

4. Patients with a concurrent or prior malignancy are ineligible unless they are
patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the
skin. Patients who have been free of disease (any prior malignancy) for greater than
five years are eligible for this study

5. Patients cannot be receiving cytochrome P450-inducing anticonvulsants (EIAEDs; e.g.,
phenytoin, carbamazepine, phenobarbital, primidone, oxcarbazepine) and must not have
taken them for at least 10 days

Phase I Ineligibility Criteria (Phase I Patients ONLY)

1. Patients who have had repeat craniotomy for tumor therapy after receiving RT and TMZ
treatment

2. Patients who received other chemotherapeutics or investigational agents in addition
to their radiation therapy and concomitant temozolomide treatment. Patients who have
received Gliadel wafers are eligible for this study