• To evaluate plasma pharmacokinetics and pharmacodynamic effects of XL765 and temozolomide when administered in combination [ Time Frame: Assessed during periodic visits ] [ Designated as safety issue: No ]
• To evaluate preliminary efficacy of XL765 in combination with temozolomide in adults with anaplastic gliomas or glioblastoma [ Time Frame: Assessed during periodic visits ] [ Designated as safety issue: No ]

The purpose of this study is to determine the safety and tolerability of XL765 in combination with Temozolomide in adults with anaplastic gliomas or glioblastoma on a stable Temozolamide maintenance dose. XL765 is a new chemical entity that inhibits the kinases PI3K and mTOR. In preclinical studies, inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells, whereas inactivation of mTOR has been shown to inhibit the growth of tumor cells. Temozolomide (TMZ, Temodar®) is an orally administered alkylating agent with activity against malignant gliomas. It is approved by the Food and Drug Administration for the following indications: 1) treatment of newly diagnosed glioblastoma multiforme (GBM) patients when given concomitantly with radiotherapy and then as maintenance treatment; 2) refractory anaplastic astrocytoma (AA), ie, patients who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine. Temozolomide is commonly used in the treatment of other anaplastic gliomas (AG) including oligodendroglial tumors and mixed gliomas.

• Mixed Gliomas
• Malignant Gliomas
• Glioblastoma Multiforme

• Drug: XL765
• Drug: Temozolomide

Inclusion Criteria:

• Histologically confirmed intracranial anaplastic glioma or glioblastoma
• Currently on a temozolomide dose of 200 mg/m2/day administered on Days 1-5 of a 28-day cycle for at least 4 weeks, without unacceptable toxicity or progression.
• Karnofsky performance status of 60 or more.
• Adequate organ and bone marrow function as defined by hematological and serum chemistry limits
• At least18 years old.
• Both men and women must practice adequate contraception
• Informed consent

Exclusion Criteria:

• Progressed while on temozolomide.
• Restriction of some therapies/medications within specific timeframes prior to enrollment and during the study including cytotoxic chemotherapy other than temozolomide, biologic agents, nitrosoureas or mitomycin C, small-molecule kinase inhibitors, non-cytotoxic hormonal agents, prior therapy with a PI3K and/or mTOR inhibitors, radiation therapy
• Not recovered from the toxic effects of prior therapy
• Pregnant or breast feeding
• History of diabetes mellitus.
• Currently taking enzyme-inducing anticonvulsant medication or valproic acid
• Uncontrolled intercurrent illness
• Congestive heart failure, unstable angina, or a myocardial infarction within 3 months of entering the study.
• HIV positive
• Diagnosis of another malignancy may exclude subject from study