A Phase 1 Dose Finding Study of the Safety and Pharmacokinetics of XL184 Administered Orally in Combination With Temozolomide and Radiation Therapy in the First Line Treatment of Subjects With Glioblastoma

Inclusion Criteria:

- Histologically confirmed diagnosis of Grade 4 astrocytic tumor, which includes
glioblastoma, giant cell glioblastoma, gliosarcoma, and glioblastoma with
oligodendroglial components.

- Must have had a partial or complete surgical resection of the Grade 4 astrocytic
tumor.

- Subjects in Arm 1 must have had no previous treatment except surgery (ie, no previous
RT, local chemotherapy, or systemic therapy). Subjects must meet certain other
eligibility requirements.

- Subjects in Arm 2 must have completed a standard first line regimen of concurrent TMZ
and RT for newly diagnosed GB, followed by a rest phase, and has not had any other
previous treatment except surgery (including any other regimens of RT and local or
systemic chemotherapy). Subjects must meet certain other eligibility requirements.

- Subjects must be able to undergo serial MRIs (computerized tomography [CT] may not
substitute for magnetic resonance imaging [MRI]).

- Must be ≥ 18 years old.

- Must have a Karnofsky performance status of ≥ 70% and the ability to swallow whole
capsules

- Must have no other diagnosis of malignancy (except surgically excised non-melanoma
skin cancer or carcinoma in situ of the cervix, treated early stage prostate cancer,
or a malignancy diagnosed ≥ 2 years previously with no current evidence of disease
and no therapy within two years prior to enrollment on this study).

- Must be capable of understanding and complying with the protocol requirements and has
signed the informed consent document.

- Sexually active fertile subjects (male and female) must agree to use accepted methods
of contraception during the course of the study and for 3 months after the last dose
of study drug(s).

- Female subjects of childbearing potential must have a negative pregnancy test at
screening.

Exclusion Criteria:

- Subject has received prior systemic chemotherapy or RT (Arm 1) or prior systemic
chemotherapy other than TMZ (Arm 2), biologic agents, or any other type of
investigational agent for the treatment of brain tumors. Subjects who have
progressed on TMZ are not eligible.

- Subject has evidence of acute intracranial or intratumoral hemorrhage > Grade 1
either by MRI or CT scan. Subjects with resolving hemorrhage changes, punctate
hemorrhage, or hemosiderin may enter the study.

- Subject has serious intercurrent illness such as: hypertension despite optimal
treatment, or significant cardiac arrhythmias; or a recent history of serious disease
such as symptomatic congestive heart failure, or abdominal fistula or
gastrointestinal (GI) perforation within 6 months, prior to starting study treatment.

- Subject has had major surgery within 28 days prior to starting study treatment, or
had non water-tight dural closure during previous surgery, or has unhealed wounds
from previous surgery.

- Subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding.

- Subject is pregnant or breastfeeding.

- Subject is known to be positive for the human immunodeficiency virus (HIV) (a test
for HIV at screening is not required).

- Subject has a previously-identified allergy or hypersensitivity to components of
either the XL184 or TMZ formulations.

- Subject is unable or unwilling to abide by the study protocol or cooperate fully with
the investigator or designee.