An Open-Labeled, Non-Randomized Phase I Study of Alvocidib (Flavopiridol) Administered With Irinotecan (CPT-11) and Fluorouracil/Leucovorin in Patients With Advanced Solid Tumors
I. Determine the maximum tolerated dose of flavopiridol (alvocidib) when administered with
irinotecan hydrochloride, fluorouracil, and leucovorin calcium in patients with locally
advanced or metastatic solid tumors.
II. Determine the clinical pharmacokinetics of fluorouracil when administered in this
regimen in these patients.
III. Determine, preliminarily, the therapeutic activity of this regimen in these
patients.Correlate the role of p21 and Drg1 with apoptosis and treatment response in
patients receiving this regimen.
OUTLINE: This is a dose-escalation study of alvocidib and fluorouracil (5-FU).
Patients receive irinotecan hydrochloride IV over 90 minutes followed 5 hours later by
leucovorin calcium IV over 2 hours and alvocidib IV over 1 hour immediately followed by 5-FU
IV continuously over 48 hours beginning on day 1 of weeks 1, 3, and 5. Courses repeat every
6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6
patients receive escalating doses of alvocidib and 5-FU 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. Ten additional patients are treated at the MTD.
PROJECTED ACCRUAL: A total of 27-77 patients will be accrued for this study within 11-38
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of biweekly flavopiridol when given in conjunction with irinotecan hydrochloride, fluorouracil, and leucovorin
Gary K. Schwartz
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
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