A Phase 2 Study of XL184 in Subjects With Progressive or Recurrent Glioblastoma Multiforme in First or Second Relapse

Inclusion Criteria:

- The subject has locally determined histologically confirmed diagnosis of Grade 4
astrocytic tumor.

- The subject has received prior standard radiation for Grade 3 or 4 astrocytic tumor.

- The subject has received prior temozolomide therapy for Grade 3 or 4 astrocytic tumor
(if in first relapse, the subject must have received temozolomide until progression,
intolerance, or completion of planned therapy; if in second relapse, the subject must
have received temozolomide until progression, intolerance, or completion of planned
therapy either for first-line treatment or for treatment after first relapse).

- The subject is in first or second Grade 4 relapse, defined as having one or two
progressions as Grade 4 astrocytic tumor since the original diagnosis of any grade
glioma.

- The subject must have a baseline brain MRI scan within 14 days prior to first dose of
XL184 while either not receiving glucocorticoids during the 5 days prior to the
baseline MRI scan or on a stable dose of glucocorticoids during the 5 days prior to
the baseline MRI scan.

- Subjects having undergone recent resection or biopsy of tumor will be eligible as
long as all of the following conditions apply: First dose of XL184 occurs at least 28
days after surgery, the subject has recovered from the effects of surgery, and the
subject has measurable residual disease.

- The subject is at least 18 years old.

- The subject has a KPS (Karnofsky Performance Scale) of ≥ 70%.

- The subject is capable of understanding the protocol and has signed the informed
consent document.

- The subject has adequate organ and marrow function.

- Sexually active subjects (male and female) must agree to use medically accepted
methods of contraception during the course of the study and for 3 months following
discontinuation of study drug.

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

Exclusion Criteria:

- The subject has received non-standard radiation therapy for glioblastoma,
non-anti-angiogenic therapy (including investigational agents, small-molecule kinase
inhibitors, and biologic agents) or non-cytotoxic hormonal agent within 28 days of
the first scheduled dose of XL184 or mitomycin C within 42 days of the first
scheduled dose of XL184, other investigational therapy (including agents not
specified above) within 28 days of the first scheduled dose of XL184, or prior
treatment with nitrosoureas (including carmustine wafer) at any time.

- Some subjects may not have had any prior VEGF- or VEGFR2-based anti-angiogenic
therapy (such as bevacizumab, cediranib, or pazopanib).

- Some subjects may not have had bevacizumab within 14 days of the first scheduled dose
of XL184.

- The subject is receiving warfarin (or other coumarin derivatives) at study entry and
unable to switch to low molecular weight heparin.

- The subject has evidence of acute intracranial or intratumoral hemorrhage either by
MRI or computerized tomography (CT) scan. Subjects with resolving hemorrhage changes,
punctate hemorrhage, or hemosiderin may enter the study.

- The subject is unable to undergo MRI scan (eg, has pacemaker).

- The subject has received enzyme-inducing anti-epileptic agents within 2 weeks before
the first dose of XL184 (eg, carbamazepine, phenytoin, phenobarbital, primidone).

- The subject has not recovered to National Cancer Institute Common Terminology
Criteria for Adverse Events (CTCAE) v3.0 Grade ≤ 1 from adverse events (AEs) due to
surgery, antineoplastic agents, investigational drugs, or other medications that were
administered before study enrollment.

- The subject has evidence of wound dehiscence.

- The subject is pregnant or breast-feeding.

- The subject has serious intercurrent illness, such as uncontrolled hypertension,
unhealed wounds from recent surgery or cardiac arrhythmias or a recent history of
significant disease such as either symptomatic congestive heart failure or unstable
angina pectoris within the past 3 months, myocardial infarction within the past 6
months, or active infection requiring systemic treatment/hospitalization within 2
weeks of the first scheduled dose of XL184

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

- The subject has received any live virus vaccine within 28 days or any inactivated
vaccine within 7 days prior to first dose of XL184.

- The subject has had another diagnosis of malignancy (unless nonmelanoma skin cancer,
in situ carcinoma of the cervix, or a malignancy diagnosed ≥ 2 years previously) or
currently has evidence of malignancy (unless non-melanoma skin cancer or in situ
carcinoma of the cervix).

- The subject has a known allergy or hypersensitivity to any of the components of the
XL184 formulations.