A Pharmacokinetic Study Evaluating the Safety, Tolerability and Maximally Tolerated Dose of 7-Day Continuous Infusions of L-778,123 in Patients With Recurrent of Refractory Solid Malignancies
OBJECTIVES: I. Determine the maximum tolerated dose of L-778,123 in patients with recurrent
or refractory solid tumors. II. Evaluate the safety and tolerability of L-778,123 including
qualitative, quantitative, and dose limiting toxicity in these patients. III. Assess the
pharmacokinetic profile of this regimen in these patients. IV. Evaluate the radiologic or
tumor marker responses to treatment in these patients. V. Evaluate the relationship between
ras mutations and response to treatment in these patients. VI. Determine the relationship
between plasma drug levels and farnesylation assay results.
OUTLINE: This is a dose escalation study. Patients receive continuous infusions of L-778,123
over 7 days every 3 weeks. Treatment continues in the absence of disease progression or
unacceptable toxic effects. All patients are observed for at least 1 week after the 7 day
infusion of L-778,123 prior to subsequent dose escalation. Cohorts of 3-6 patients receive
escalating doses of L-778,123 until the maximum tolerated dose (MTD) is reached. MTD is
defined as the dose at which no more than 2 of 6 patients experiences dose limiting
toxicities. Patients are followed until death.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Primary Purpose: Treatment
David R. Spriggs, MD
Memorial Sloan-Kettering Cancer Center
United States: Federal Government
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|