Safety Study of XL184 (Cabozantinib) in Combination With Temozolomide and Radiation Therapy in the Initial Treatment of Adults 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.