Inclusion Criteria:

• Resolution of all acute toxic effects of prior chemotherapy or radiotherapy or surgical procedures to NCI CTCAE Version 3.0 grade ≤1.

• Adequate organ function as defined by the following criteria:

  • Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) ≤3 x local laboratory upper limit of normal (ULN), or AST and ALT ≤3 x ULN if liver function abnormalities are due to underlying malignancy
  • Total serum bilirubin ≤1.5 x ULN
  • Absolute neutrophil count (ANC) ≥1500/µL
  • Platelets ≥100,000/µL
  • Hemoglobin ≥9.0 g/dL
  • Serum calcium ≤12.0 mg/dL
  • Serum creatinine ≤1.5 x ULN
• Patients must have histologically or neuroradiographically recurrent anaplastic astrocytoma (AA) or glioblastoma (GBM). Must have had prior pathologic confirmation of primary tumor histology.
• Must be ≥ 18 years old.
• Must have a KPS ≥ 60%
• Measurable disease per MacDonald criteria required using contrast enhanced cranial MR.
• Life expectancy ≥ 12 weeks.
• Must sign and date an IRB approved informed consent stating that he or she is aware of the neoplastic nature of the disease. Must willingly provide written consent after being informed of procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests and accessible for follow-up.
• Must have undergone surgery documenting tumor histology though repeat surgery at time of tumor recurrence is not mandatory.
• Must have received prior external beam radiotherapy.
• Patients may have received one or two prior salvage chemotherapy and may have received adjuvant chemotherapy following initial surgery.
• May not have received prior stereotactic radiotherapy.
• May have been treated with Gliadel at initial surgery only.

Exclusion Criteria:

• Major surgery or radiation therapy within 4 weeks of starting study treatment.
• NCI CTCAE grade 3 hemorrhage within 4 weeks of starting study treatment.
• History of or known spinal cord compression or carcinomatous meningitis, or evidence of leptomeningeal disease on screening CT or MRI scan.
• Any of the following within 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
• Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2.
• Prolonged QTc interval on baseline EKG.
• Hypertension that cannot be controlled by medications (>150/100 mm Hg despite optimal medical therapy).
• Pre-existing thyroid abnormality with thyroid function that cannot be maintained in normal range with medication.
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection.
• Concurrent treatment on another clinical trial. Supportive care trials or non-treatment trials, e.g. QOL, are allowed.
• Concomitant use of ketoconazole and other agents known to inhibit CYP3A4.
• Concomitant use of theophylline and phenobartital and/or other agents metabolized by the cytochrome P450 system.
• Ongoing treatment with therapeutic doses of Coumadin (low dose up to 2 mg po daily for thrombo-prophylaxis is allowed).
• Pregnancy or breastfeeding. Female subjects must be surgically sterile, postmenopausal, or must agree to use effective contraception during the period of therapy. Female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment. Male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with interpretation of study results, and in the judgment of investigator would make subject inappropriate for entry into this study.
• Patients having been treated with 3 or more salvage regimens.
• Patients with a second active malignancy or diagnosis of other cancer within 3 years of enrollment, except for surgically cured basal cell carcinoma, or in situ carcinoma of the cervix.
• Mentally incapacitated patients or psychiatric illness that would prevent them from giving informed consent.
• Poorly controlled diabetes, hepatitis infection, uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure, and myocardial infarction within previous six months, or serious uncontrolled cardiac arrhythmia.
• Known to be HIV positive or to have an AIDS-related illness.
• Patients with an active infection that is not adequately controlled with antibiotics.
• Patients with other severe concurrent disease, which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
• Known sensitivity to any of the products to be administered during treatment.
• Currently enrolled in another clinical trial or patients who have participated in a trial of an investigational device or drug within the last 30 days.