The purpose of this study is to measure what effect the study drug XL765 (SAR245409) or the study drug XL147 (SAR245408) has on tumor tissue in subjects with recurrent glioblastoma (GB) who are candidates for surgical resection. XL765 (SAR245409) and XL147 (SAR245408), the two investigational agents examined in this study, XL147 (SAR245408) is a potent inhibitor of PI3 Kinase (PI3K) and XL765 (SAR245409) is a dual PI3K and mTOR inhibitor. In preclinical studies, inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Supplied as 10-mg and/or 50-mg capsules
Supplied as 100-mg, 150-mg and/or 200-mg tablets
Investigational Site Number 840001
Los Angeles, California, United States
Investigational Site Number 840003
San Francisco, California, United States
Investigational Site Number 840004
Boston, Massachusetts, United States
Investigational Site Number 840002
New York, New York, United States
To explore the biological effect of XL765 and XL147 measured by modulation of PI3K/ mTOR pathway readouts in GB tumor tissue
Time frame: Assessed between 10 and 28 days after initiation of study drug
To examine the safety profile of daily oral administration of XL765 and XL147 in subjects with recurrent GB
Time frame: Assessed at every visit to the study clinic for the duration of subject's treatment
To determine the levels of XL765 and XL147 in plasma and GB tumor tissue
Time frame: Assessed at periodic visits between 10 and 28 days after initiation of study drug for the duration of subject's treatment
To assess the anti-proliferative and pro-apoptotic effects of XL765 and XL147 on tumor cells
Time frame: Assessed at periodic visits to the study clinic for the duration of subject's treatment
To measure changes in tumor after surgery in subjects receiving XL765 and XL147
Time frame: Assessed at periodic visits following surgery 10 to 28 days after initiation of study drug for the duration of subject's treatment
To conduct genetic analyses of GB tumor tissue comparing, where feasible, tumor tissue removed during the on-study resection with tissue removed during the initial surgical resection
Time frame: Assessed 10 to 28 days after initiation of study drug
To evaluate the pharmacodynamic effects of XL765 and XL147 in blood and/or blood cells for identification and characterization of surrogate biomarkers associated with the biological effects of XL765 and XL147
Time frame: Assessed at periodic visits to the study clinic
To explore the relationship between clinical response and genomic and proteomic biomarkers in the PI3K and EGFR pathways
Time frame: Duration of the study (approximately 2 years)
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