A Phase I Pharmacokinetic Trial of LY231514 Administered Intravenously Every 3 Weeks in Advanced Cancer Patients With Varying Degrees of Renal Function
OBJECTIVES: I. Determine the toxic effects and maximum tolerated dose (MTD) of LY231514 in
patients with metastatic or locally advanced solid tumors and varying degrees of renal
function. II. Determine the recommended dose for LY231514 in this patient population. III.
Examine the effects of renal dysfunction on the pharmacokinetics of LY231514 in this patient
population. IV. Examine the relationship between impaired renal function, drug exposure, and
drug effects in these patients. V. Gather data for development of a LY231514 dosing nomogram
based on renal function. VI. Collect preliminary data regarding antitumor effects of
LY231514 in this patient population.
OUTLINE: This is an open label, dose escalation study. Patients are stratified according to
renal function. Group 1 consists of patients with normal renal function, and groups 2, 3,
and 4 consist of patients with mild, moderate, and severe renal impairment. All patients
receive LY231514 IV over 10 minutes every 3 weeks. Treatment continues in the absence of
disease progression or unacceptable toxicity. Cohorts of 3-6 patients are treated with
escalating doses of LY231514 within each treatment group. If dose limiting toxicity (DLT) is
observed in 1 of 3 patients at a given dose level, then 3 additional patients are studied.
The maximum tolerated dose is defined as the dose level at which less than 2 of 6 patients
experience DLT. Patients are followed until death.
PROJECTED ACCRUAL: Up to 50 patients will be accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Eric K. Rowinsky, MD
San Antonio Cancer Institute
United States: Food and Drug Administration
|San Antonio Cancer Institute||San Antonio, Texas 78229-3264|