An Open-Labeled, Non-Randomized Phase I Study of Alvocidib (Flavopiridol) Administered With Irinotecan (CPT-11) and Cisplatin in Patients With Advanced Solid Tumors
I. Determine the maximum tolerated dose of flavopiridol (alvocidib), irinotecan (irinotecan
hydrochloride), and cisplatin in patients with advanced solid tumors.
II. Determine the clinical pharmacokinetics of this regimen in these patients. III.
Determine, preliminarily, the therapeutic activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study.
Patients are stratified according to the number of prior treatment regimens (0 or 1 vs more
than 1). Patients receive irinotecan hydrochloride intravenously (IV) over 30 minutes
followed immediately by cisplatin IV over 30 minutes followed 7 hours later by alvocidib IV
over 1-4.5 hours weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease
progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of cisplatin, alvocidib, and irinotecan
hydrochloride until the maximum tolerated dose (MTD) of each is determined. The MTD is
defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience
dose-limiting toxicity. Once the MTD is determined, 12 additional patients are treated at
the recommended phase II dose.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD alvocidib when administered in conjunction with irinotecan hydrochloride and cisplatin
Defined as the dose one level below the dose at which two or more of the patients in the initial cohort experience dose limiting toxicity (DLT) during the first treatment course. DLT is defined as the occurrence of Grade 4 hematologic toxicity, Grade 3 or 4 non-hematologic toxicity including diarrhea despite antidiarrheal prophylaxis, or any delay in treatment resulting in less than 2 treatments in 3 weeks.
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
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