Inclusion Criteria

- INCLUSION CRITERIA:

Age:

Patients must be less than or equal to 21 years of age at the time of study enrollment. At
the time the MTD or the dose to be recommended for future trials is identified, up to 12
additional patients will be enrolled at that dose level to further define the toxicity
profile. Six of these patients will be less than 12 years of age and the other half will
be greater than or equal to 12 years.

Tumor:

Patients with a diagnosis of a primary CNS malignancy (including low-grade glioma) that is
recurrent or refractory to standard therapy and for which there is no known curative
therapy. All patients must have had histological verification of malignancy at initial
diagnosis or relapse, excluding patients with diffuse intrinsic brain stem tumors, optic
pathway tumors or CNS germ cell tumors with elevations of reliable serum or CSF tumor
markers (alpha-fetoprotein or beta-HCG). Patients with intrinsic pontine gliomas or optic
pathway tumors do not require histological confirmation of disease but should have
clinical and/or radiographic evidence of progression.

Performance Status:

Patients must have Karnofsky Performance Score (for patients greater than 16 years of age)
or Lansky Performance Score (for patients less than or equal to 16 years of age) greater
than or equal to 50% assessed within two weeks of study enrollment.

Neurological Status:

Patients must be able to take oral medications (either capsules or liquid). Patients with
neurologic deficits must have been stable for a minimum of 1 week prior to study entry.
Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will
be considered ambulatory for the purpose of assessing the performance score.

Prior/Concurrent Therapy:

Patients must have fully recovered from the acute toxic effects of all prior chemotherapy,
immunotherapy, or radiotherapy prior to entering this study. Recovery is defined as all
AE's, attributable to prior therapy, having improved to grade 2 or better or as outlined
below.

- Myelosuppressive chemotherapy:

- Patients must have received their last dose of known myelosuppressive anticancer
chemotherapy at least three (3) weeks prior to study registration.

- Patients must have received their last dose of nitrosourea (including Gliadel)
at least six (6) weeks prior to study registration.

- Biologic agent (anti-neoplastic): Patient must have received their last dose of other
biologic agent greater than or equal to 7 days prior to study registration.

--For agents that have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time during which adverse
events are known to occur. The duration of this interval must be discussed with the
study chair.

- Monoclonal antibody treatment: Patient must have received their last dose of
monoclonal antibody greater than or equal to 4 weeks prior to registration.

- Radiation - Patients who have had prior radiation must have had their last fraction
of:

- Craniospinal irradiation or total body irradiation greater than 3 months prior
to registration

- Local irradiation to the primary tumors or other sites (cumulative dose greater
than or equal to 40Gy) greater than 3 months prior to registration

- Palliative irradiation delivered to symptomatic metastatic sites greater than 4
weeks prior to registration.

- Stem Cell Transplant: Patient must be:

- greater than or equal to 6 months since allogeneic stem cell transplant prior to
registration

- greater than or equal to 3 months since autologous stem cell transplant prior to
registration.

- Corticosteroids: Patients who are receiving dexamethasone must be on a stable or
decreasing dose for at least 1 week prior to registration.

- Growth factors:

- Off all colony forming growth factor(s) that support platelet or white blood
cell count, number or function for at least 1 week prior to registration
(filgrastim, sargramostim, erythropoietin).

- Off Pegylated G-CSF and/or Erythropoiesis Stimulating Protein for at least 14
days prior to registration.

- Temozolomide: Patients who have received temozolomide previously are eligible for
this study if they meet all other inclusion and exclusion criteria.

Organ Function: Documented within 14 days of registration and within 7 days of starting
treatment.

- Bone Marrow:

- Hgb greater than 8 gm/dL (transfusion independent)

- Platelet count greater than 100,000/mm(3) (transfusion independent)

- Absolute neutrophil count (ANC) greater than 1,500/mm(3)

- Hepatic:

- Total Bilirubin (sum of conjugated + unconjugated) less than or equal to 1.5
times institutional upper limit of normal (ULN) for age

- SGPT (ALT) less than or equal to 2.5 times institutional ULN for age

- Serum albumin greater than or equal to 2 g/dL

- Renal:

--Creatinine clearance or radioisotope GFR greater than or equal to 70
ml/min/1.73m(2) or a serum creatinine based on age as follows:

- Age less than 5 (years): a Maximum Serum Creatinine (mg/dL) of 0.8

- Age greater than 5 (years) but less than 10: a Maximum Serum Creatinine (mg/dL) of 1

- Age greater than 10 (years) but less than 15: a Maximum Serum Creatinine (mg/dL) of
1.2

- Age greater than 15 (years): a Maximum Serum Creatinine (mg/dL) of 1.5

Pregnancy or Breast-feeding:

Patients must not be pregnant or breast-feeding. Females of reproductive potential must
have a negative serum or urine pregnancy test (within 72 hours prior to enrollment). Males
or females of reproductive potential may not participate unless they have agreed to use an
effective contraceptive method, which includes abstinence.

Signed informed consent which includes consent to participate in the required
pharmacokinetic and pharmacodynamic studies prior to registration.

EXCLUSION CRITERIA:

Concomitant Medications:

Patients receiving any of the following medications are not eligible for study entry:

- Anti-cancer therapy

- Investigational agents

Concurrent Illness:

Patients with any clinically significant, unrelated systemic illness (serious infections
or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would
compromise the patient's ability to tolerate protocol therapy or would likely interfere
with the study procedures or results.

Seizures:

Patients with uncontrolled seizures are not eligible for study entry.

Hypertension:

- Patients with inadequately controlled systemic hypertension (SBP and/or DBP greater
than 95th percentile for age and height

- Patients with a prior history of hypertensive crisis and/or hypertensive
encephalopathy

If a BP measurement prior to registration is greater than 95th percentile for age and
height, it must be rechecked and documented to be less than 95th percentile for age and
height prior to registration. If a patient falls between the height or weight percentiles,
site should average the value as appropriate. For patients greater than or equal to 18
years the normal blood pressure should be less than 140/90 mm of Hg. Patients with
hypertension are eligible if their blood pressures become less than 95th percentile for
age and height after anti-hypertensive medications.

Prior CNS ischemia and/or infarction:

Patients with documented CNS ischemia and/or infarction, whether symptomatic or discovered
incidentally without clinical symptoms, will be excluded from study participation.

Inability to Participate:

Patients with an inability to return for follow-up visits or obtain follow-up studies
required to assess toxicity to therapy.