An Open-Label, Non-Randomized Phase I Study of the Protein Kinase C Inhibitor Flavopiridol Administered in Combination With Paclitaxel in Patients With Advanced Solid Tumors
OBJECTIVES: I. Determine the maximum tolerated dose of flavopiridol when administered in
combination with paclitaxel and cisplatin in patients with refractory adult solid tumors.
II. Investigate the clinical pharmacokinetics of intravenous flavopiridol when administered
in combination with paclitaxel in these patients. III. Obtain preliminary data on the
therapeutic activity of flavopiridol when administered in combination with paclitaxel in
these patients. IV. Evaluate surrogate markers of activity such as inhibition of PKC or CDK1
in these patients.
OUTLINE: This is an open label, dose escalation study. Patients receive paclitaxel IV over 3
hours on day 1. On day 2, patients receive cisplatin IV over 20 minutes followed by a 24
hour infusion of flavopiridol. Courses are repeated every 21 days in the absence of disease
progression or unacceptable toxicity. Sequential dose escalation of flavopiridol is followed
by sequential dose escalation of cisplatin. Dose escalation in cohorts of 3-6 patients each
continues until the maximum tolerated dose (MTD) is determined. The MTD is defined as the
dose preceding that at which 2 of 6 patients experience dose limiting toxicity. Patients are
followed every 6 weeks.
PROJECTED ACCRUAL: Approximately 46-73 patients will be accrued for this study within 6 more
Primary Purpose: Treatment
Gary K. Schwartz, MD
Memorial Sloan-Kettering Cancer Center
United States: Federal Government
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