Phase I Study of Flavopiridol in Combination With 5-Fluorouracil, Leucovorin and Irinotecan in Patients With Advanced Malignancies
I. Determine the maximum tolerated dose of flavopiridol, fluorouracil, and leucovorin
calcium with or without irinotecan in patients with advanced malignancy.
II. Assess the toxic effects of these regimens in these patients. III. Determine the
clinical response in patients treated with these regimens.
OUTLINE: This a dose-escalation study of flavopiridol (FLAVO), fluorouracil (5-FU), and
irinotecan. Patients are assigned to 1 of 2 groups. Groups I and II are conducted
Group I: Patients receive FLAVO IV over 24 hours on day 1 and leucovorin calcium (CF) IV and
5-FU IV over 1.5 hours daily on days 2-5. Courses repeat every 3 weeks in the absence of
disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating
doses of FLAVO and 5-FU until the maximum tolerated doses (MTD) are determined. The MTD is
defined as the dose preceding that at which at least 2 of 6 patients experience
Group II: Once the MTDs for FLAVO and 5-FU are determined, patients receive FLAVO, CF, and
5-FU as in group I plus irinotecan IV over 1.5 hours on day 1. Courses repeat as in group I.
Cohorts of 3-6 patients receive escalating doses of irinotecan until the MTD is determined.
The MTD is defined as in group I.
Patients are followed at 3 months.
PROJECTED ACCRUAL: A maximum of 57-90 patients will be accrued for this study within 18
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number and severity of toxicity incidents of alvocidib, 5-fluorouracil, leucovorin calcium with and without irinotecan hydrochloride, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Up to 5 years
United States: Food and Drug Administration
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