A Phase I Trial of Gemcitabine Followed by a Short Infusion of Flavopiridol in Patients With Solid Tumors
I. Determine the maximum tolerated dose of gemcitabine and flavopiridol in patients with
I. Determine the safety profile and toxic effects of this regimen in these patients.
II. Determine the pharmacokinetics of flavopiridol with and without gemcitabine in these
III. Determine, using pharmacodynamic assays, the activity of flavopiridol as a cdk
inhibitor in these patients.
IV. Determine, using pharmacodynamic assays, the markers of this regimen in these patients.
OUTLINE: This is a dose-escalation, multicenter study.
Some patients receive an initial dose of alvocidib IV over 1-7 hours on day 1 (course 0).
Beginning 1 week later and for all subsequent courses, all patients receive gemcitabine
hydrochloride IV over 60-150 minutes on days 1 and 15 and alvocidib IV over 1-7 hours on
days 2 and 16. Courses repeat every 28 days in the absence of disease progression or
Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride and 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, up to 10 additional patients receive treatment at that dose.
Patients are followed at 30 days after study completion.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose-limiting toxicity (DLT) graded by National Cancer Institute (NCI) Common Toxicity Criteria
Dana-Farber Cancer Institute
United States: Food and Drug Administration
|Memorial Sloan Kettering Cancer Center||New York, New York 10021|
|Massachusetts General Hospital Cancer Center||Boston, Massachusetts 02114|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|