Inclusion Criteria:

- 18 years of age or older

- Histologically confirmed WHO grade IV astrocytoma (glioblastoma). Patients with
recurrent disease whose original pathology confirmed glioblastoma will not need
re-biopsy. Patients with prior low-grade glioma or anaplastic glioma are eligible if
histological assessment demonstrates transformation to GBM.

- The first-line regimen must have included, at a minimum, temozolomide and radiation.

- First or second episode of progressive disease.

- No more than two prior treatment regimens for progressive disease. Concurrent
temozolomide and radiation followed by monthly cycles of temozolomide is counted as
one regimen.

- For all study arms, patients must have at least 15 unstained slides or 1 tissue block
available from a prior biopsy or surgery.

- All patients must have progressive disease on contrast-enhanced brain CT or MRI as
defined by MacDonald Criteria, or have documented recurrent glioblastoma on
diagnostic biopsy. Arm A patients may continue treatment in the post-operative
period even if there is no residual contrast-enhancing tumor after surgery.

- For Arm A, patients must be candidates for surgical partial or gross-total resection.

- Interval of at least 2 weeks between prior surgical resection and adequate wound
healing.

- Interval of at least 12 weeks from prior radiotherapy unless there is either a)
histopathologic confirmation of recurrent tumor; b) new enhancement on MRI outside of
the XRT treatment field.

- Patients must have sufficient time for recovery from prior therapy

- Karnofsky Performance Status of 60% or greater

- Laboratory levels as outlined in the protocol

- Women of child-bearing potential and men must agree to use adequate contraception
prior to study entry, for the duration of study participation and for 3 months
thereafter.

Exclusion Criteria:

- Participants may not be receiving any other investigational agents

- Previously treated with an anti-VEGF agent

- For subjects in Arm A: if the diagnostic pathology of the biopsy specimen is not
consistent with recurrent glioblastoma then the subject will be taken off study and
be replaced with another subject that meets the inclusion criteria and is eligible
for surgical resection

- Any surgery within 2 weeks of baseline disease assessments, or not fully recovered
from any side effects of previous procedures

- Any clinically significant gastrointestinal abnormalities, which may impair intake,
transit or absorption of the study drug, such as the inability to take oral
medications in tablet form.

- Any psychiatric or cognitive disorder that would limit the understanding or rendering
of informed consent and/or compromise compliance with the requirements of this
protocol

- Concomitant use of CYP3A4/5 inhibitors during the treatment phase of the study and
within 72 hours prior to starting study drug administration

- Concomitant use of CYP3A4/5 inducers, which include enzyme inducing antiepileptic
drugs during treatment phase of the study and within 2 weeks prior to starting
treatment.

- Uncontrolled or significant cardiovascular disease

- Prior stereotactic radiotherapy, convection enhanced delivery or brachytherapy as
gliosis/scarring from these modalities may limit delivery

- Pregnant or breast feeding women

- HIV-positive individuals on combination antiretroviral therapy

- Other severe acute or chronic medical condition or laboratory abnormality