An Open-Labeled, Non-Randomized Phase I Study of Alvocidib (Flavopiridol) Administered With Oxaliplatin and Fluorouracil/Leucovorin in Patients With Advanced Solid Tumors
I. Determine the maximum tolerated dose of flavopiridol when given in combination with
oxaliplatin, fluorouracil, and leucovorin calcium in patients with advanced solid tumors.
II. Determine the pharmacokinetics of this regimen in these patients. III. Determine,
preliminarily, the therapeutic activity of this regimen in these patients.
IV. Determine the dose-limiting toxicity and the recommended phase II dose of flavopiridol
when administered with this regimen in these patients.
V. Determine the safety and tolerability of this regimen in these patients. VI. Correlate
p21, p53, and apoptotic markers with response in patients treated with this regimen.
OUTLINE: This is a non-randomized, open-label, dose-escalation study of flavopiridol.
Patients receive alvocidib intravenously (IV) over 1 hour, oxaliplatin IV over 2 hours,
leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 48 hours on days
1, 15, and 29. Courses repeat every 42 days in the absence of disease progression or
Cohorts of 3-6 patients receive escalating doses of alvocidib until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity. Once the MTD is determined, the cohort is
expanded and an additional 10 patients are treated at that dose.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of biweekly alvocidib when given in conjunction with oxaliplatin, 5-fluorouracil, and leucovorin calcium
Defined as the dose level immediately preceding the dose where 2 or more patients experienced dose-limiting toxicity.
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
|Memorial Sloan Kettering Cancer Center||New York, New York 10021|