A Phase I Study of the Cyclin-Dependent Kinase (CDK)/Protein Kinase C (PKC) Inhibitor UCN-01 (NSC 638850) in Combination With 5-Fluorouracil in Patients With Advanced Solid Tumors
- Determine the maximum tolerated dose, dose limiting toxicity, and toxicity profile of
fluorouracil with UCN-01 in patients with advanced or refractory solid tumors.
- Assess the clinical pharmacokinetics of this regimen and correlate with observed
toxicities in these patients.
- Obtain preliminary data on the therapeutic activity of this regimen in these patients.
OUTLINE: This is a dose escalation study of fluorouracil.
Patients receive fluorouracil IV over 24 hours on days 1, 8, 15, and 22. Patients receive an
initial dose of UCN-01 IV over 72 hours beginning on day 2 during course 1 and then
maintenance UCN-01 IV over 36 hours beginning on day 2 during subsequent courses. Treatment
repeats every 4 weeks for at least 2 courses in the absence of disease progression or
Cohorts of 3-6 patients receive escalating doses of fluorouracil until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6
patients experience dose limiting toxicity.
PROJECTED ACCRUAL: Approximately 6-48 patients will be accrued for this study within
approximately 14 months.
Primary Purpose: Treatment
Gary K. Schwartz, MD
Memorial Sloan-Kettering Cancer Center
United States: Federal Government
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|