This study would test how much of the new drug, AZD1775, is present in tumor, blood, and skin after one dose of the drug. The purpose of the study is not to treat the tumor, but to see if the drug actually gets into the tumor cells. This study does not replace routine cancer treatment.
Patients will be administered one dose of AZD1775 prior to surgical resection of their tumor. There will be 2 portions of this trial, referred to as Part 1 and Part 2. Part 1 will involve a dose escalation strategy where 3 separate doses (100, 200, and 400mg) will be evaluated. Each dose cohort will involve 4 patients. Surgery, with tissue harvest for determination of both tissue drug level and biomarker evaluation, will occur at 8 hrs post drug administration. Part 2 will determine the potential tumor drug level and PD effects at various time intervals after drug administration of a single select drug dose. Currently, we are planning to use a dose (200 mg) that has been deemed safe when used in combination with cytotoxic therapy. However, if results from Part 1 suggest an alternate dose may be preferable, we will consider using that alternate dose in Part 2. Dosing will be followed by surgical resection at 2-4 hrs and at 22-26 hrs post dose.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
20
All patients receive a single dose of the oral study drug prior to surgery for resection of GBM.
Barrow Neurological Institute at St. Joseph's Hospital Medical Center
Phoenix, Arizona, United States
Plasma concentration of AZD1775 following single dose of AZD1775
Will be summarized using descriptive statistics
Time frame: at baseline, 2-4, 8-12, and 22-26 hours following single dose of AZD1775
Intratumoral concentration of AZD1775
Will be summarized using descriptive statistics
Time frame: up to day of surgery
Degree of CDC2 (Tyr15) phosphorylation in tissue
Will be summarized using descriptive statistics
Time frame: at baseline and up to 26 hours post dosing
Number of GBM cells in M-phase of cell cycle (PH3)
Will be summarized using descriptive statistics
Time frame: at baseline and up to 26 hours post dose AZD1775
Presence of double-strand DNA damage (γH2AX).
Will be summarized using descriptive statistics
Time frame: at baseline and up to 26 hours post dose AZD1775
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