Inclusion Criteria

Inclusion criteria:

Phase I

- Patients are on EIAC for a minimum of 15 days. Patients may be on more than one
anti-convulsant (AC). At least one of the ACs must be an EIAC.

- Patients with anaplastic astrocytoma, anaplastic oligodendroglioma, mixed anaplastic
oligoastrocytoma, glioblastoma multiforme, or gliosarcoma at recurrence

- Patients whose diagnostic pathology confirmed these pathologies will not need
re-biopsy

- Patients with prior low-grade glioma are eligible if histologic assessment
demonstrates transformation to Grade III or IV malignant glioma Phase II

- Patients must have histologically confirmed glioblastoma multiforme or gliosarcoma
in first or second recurrence.

- Patients may not have received more than two prior cytotoxic chemotherapy containing
regimen.

- Patients must not have received prior treatment with VEGFR, ErbB1, ErbB2 inhibitors
including but not limited to PTK-787, Sorafenib, Sutent, Tarceva, Iressa, Erbitux,
and Herceptin. Prior Avastin therapy is permitted provided three months has elapsed
before Day 1, Treatment Period 1.

- Tumor tissue must be analyzed for PTEN and epidermal growth factor receptor (EGFR)
vIII prior to dosing.

- Patients with prior low-grade glioma are eligible if histologic assessment
demonstrates transformation to Grade IV malignant glioma.

- Patients must not be on an EIAC. NOTE: Once the (optimally tolerated regimen) OTR in
Phase I is determined and all patients in the expanded cohort have completed 1
treatment period then patients on EIAC may be enrolled in the Phase II component of
the study.

Phase I and II

- Male or female, age at least 18 years of age.

- Eastern Cooperative Oncology Group (ECOG) status 0 to 1 as per protocol.

- Clinical lab results as per protocol

- Has a left ventricular ejection fraction (LVEF) at least 50% based on echocardiogram
(ECHO) or Multi Gated Aquisition (MUGA) or within the institutional normal range.

- Adequate renal function

- Creatinine clearance more than 50 mL/min as calculated by the Cockcroft-Gault formula
as per protocol.

- Urine Protein Creatinine (UPC) ratio of less than or equal to 1 as per protocol.

- Able to swallow and retain oral medications.

- A woman is eligible to enter and participate in the study if she is of:

- Non-childbearing potential (i.e., physiologically incapable of becoming pregnant),
including any female who:

- Has had a hysterectomy,

- Has had a bilateral oophorectomy (ovariectomy),

- Has had a bilateral tubal ligation,

- Is post-menopausal (total cessation of menses for at least 1 year)

- Childbearing potential, has a negative serum pregnancy test at screening, and
agrees to use adequate contraception. Acceptable contraceptive methods, when used
consistently and in accordance with both the product label and the instructions of
the physician, are as follows:

- An intrauterine device (IUD) with a documented failure rate of less than 1% per year.

- Vasectomized partner who is sterile prior to the female patient's entry and is the
sole sexual partner for that female.

- Double-barrier contraception (condom with spermicidal jelly, foam suppository, or
film; diaphragm with spermicide; or male condom and diaphragm with spermicide).

- A man with a female partner of childbearing potential is eligible to enter and
participate in the study if he uses a barrier method of contraception or abstinence
during the study.

- If sexually active, patients will continue the recommended contraceptive measures for
the duration of the treatments and for 28 days following discontinuation of therapy.

- Signed informed consent approved by the Institutional Review Board prior to patient
entry.

Exclusion criteria:

- Poorly controlled hypertension as per protocol. NOTE: Initiation or adjustment of BP
medication is permitted prior to study entry provided that patient has two
consecutive BP readings less than 140/90 mmHg each separated by a minimum of 24 hrs.
These readings need to be collected prior to enrolment.

- Concurrent severe and/or uncontrolled medical disease (e.g. uncontrolled diabetes,
congestive cardiac failure, poorly controlled hypertension, history of labile
hypertension, history of poor compliance with antihypertensive regimen, chronic renal
disease, or active uncontrolled infection) that could compromise participation in the
study.

- History of myocardial infarction, admission for unstable angina, cardiac angioplasty
or stenting within three months of Day 1, Treatment Period 1.

- Has Class III or IV heart failure as defined by the New York Heart Association (NYHA)
functional classification system as per protocol.

- QTc prolongation defined as a corrected QT (QTc) interval greater than or equal to
470 milliseconds.

- History of venous or arterial thrombosis within 3 months of Day 1, Treatment Period
1.

- Current use of therapeutic warfarin. NOTE: both low molecular weight heparin and
prophylactic low-dose warfarin are permitted; however, prothrombin time/partial
thromboplastin time (PT/PTT) must meet above inclusion criteria.

- Excessive risk of bleeding as defined by stroke within the prior 6 months, history of
central nervous system (CNS) or intraocular bleed, or septic endocarditis.

- Evidence of intratumor hemorrhage on pretreatment diagnostic imaging, except for
stable post-operative Grade 1 hemorrhage.

- Active systemic bleeding, such as gastrointestinal bleeding or gross hematuria.

- Female patients who are pregnant or breast feeding.

- Acute or chronic liver disease (i.e., hepatitis, cirrhosis).

- Patients who received investigational drugs less than 21days prior to Day 1,
Treatment Period 1, or who have not recovered from the toxic effects of such therapy.

- Patients who received chemotherapy less than or equal to 21days prior (6 weeks for
prior nitrosourea or mitomycin C) to Day 1, Treatment Period 1, or who have not
recovered from the toxic effects of such therapy.

- Patients who received radiation therapy less than or equal to 12 weeks prior to Day
1, Treatment Period 1, or who have not recovered from the toxic effects of such
therapy as per protocol.

- Patients who received biologic, immunotherapeutic or cytostatic agents less than or
equal to 14 days prior to Day 1, Treatment Period 1, or who have not recovered from
the toxic effects of such therapy.

- Patient is less than 3 years free of another primary malignancy except: if the other
primary malignancy is not currently clinically significant or requiring active
intervention. Patients with a history of completely resected non-melanoma skin
cancer or successfully treated in situ carcinoma are eligible.

- Surgical resection of brain tumor or any other surgery less than or equal to 21 days
prior to Day 1, Treatment Period 1, or who have not recovered from side effects of
such a procedure. Patients who undergo stereotactic biopsy less than or equal to 14
days prior to Day 1 of Treatment Period 1, or who have not recovered from side
effects of such a procedure.

- Patients with any Grade of intraparenchymal CNS hemorrhage. Exceptions include Grade
1 intraparenchymal hemorrhage in the immediate post-operative period, or Grade 1
intraparenchymal hemorrhage that has been stable for at least 3 months.

- Patients unwilling to or unable to comply with the protocol.

- Any serious and/or unstable pre-existing medical, psychiatric, or other condition
(including lab abnormalities) that could interfere with patient safety or obtaining
informed consent.

- History of malabsorption syndrome, disease significantly affecting gastrointestinal
function or major resection of the stomach or small bowel that could affect
absorption, distribution, metabolism or excretion of study drugs. Has any unresolved
bowel obstruction or diarrhea.

- Psychological, familial, sociological, or geographical conditions that do not permit
compliance with the protocol.

- Is on any specifically prohibited medication or requires any of these medications
during treatment.