Trial Information

Determination of Optimal O6-Benzylguanine Dose to Achieve O6-Alkylguanine-DNA Alkyltransferase Depletion in Patients With Surgically Resectable Solid Tumors

OBJECTIVES: I. Determine the minimal O6-benzylguanine (O6-BG) dose required to deplete tumor
activity to less than 10 fmol/mg protein at a specified time after administration in
patients with surgically resectable solid tumors. II. Correlate tumor tissue AGT depletion
with AGT depletion in peripheral blood mononuclear cells (PBMC) obtained at a specified time
after O6-BG administration in these patients.

OUTLINE: This is a dose escalation study. Patients receive a single dose of O6-benzylguanine
(O6-BG) IV over 1 hour at one of two dose levels. Patients undergo surgery 16-20 hours after
administration of O6-BG. Up to 13 patients receive the lower dose level of O6-BG. If more
than 3 patients have detectable AGT levels, additional patients receive the higher dose. The
optimal biologic dose (OBD) is defined as the lowest dose level at which at least 11 of 13
patients have AGT activity less than 10 fmol/mg protein after O6-BG dosing. Patients are
followed at 1 and 3 weeks post surgery.

PROJECTED ACCRUAL: A total of 13-26 patients will be accrued for this study over
approximately 10 months.