Phase I Trial of EF5, an Agent for the Detection of Hypoxia
I. Determine the optimal dose of etanidazole derivative EF5 that is safely tolerated and
provides optimal signal-to-noise ratio in patients with solid tumors.
II. Determine the toxic effects of EF5 in this patient population. III. Determine the
pharmacokinetics of EF5 in this patient population. IV. Determine the dose of EF5 that
provides a mean signal-to-noise ratio (maximum binding in anoxia to minimum binding) of 75.
V. Determine the relationship between tumor oxygenation by EF5 binding and needle electrode
VI. Compare the levels of EF5 binding in regions of low and high blood flow.
OUTLINE: This is a dose-escalation study.
Patients receive etanidazole derivative EF5 IV over 1-2 hours beginning approximately 24
hours prior to surgery. Tumors are then resected or biopsied after Eppendorf needle
Cohorts of 6 patients receive escalating doses of EF5 until the maximum tolerated dose (MTD)
or optimal dose is determined. The MTD is defined as the dose preceding that at which 2 or
more patients experience dose-limiting toxicity. The optimal dose is defined as the dose
level at or below the MTD and results in a signal-to-noise ratio of 75 or greater. Thirty
additional patients are treated at the optimal dose.
Patients are followed at 30-45 days post EF5 infusion.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Pharmacokinetics parameters including estimation of Cmax, half-life, and area under the time-concentration curve (AUC)
Pre-dose, 1, 24, and 28 hours
Stephen Michael Hahn
Abramson Cancer Center of the University of Pennsylvania
United States: Food and Drug Administration
|Abramson Cancer Center of the University of Pennsylvania||Philadelphia, Pennsylvania 19104-4283|