Study of XL184 (Cabozantinib) in Adults With Glioblastoma Multiforme

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.