An Open-Labeled, Non-Randomized Phase I Study Of Flavopiridol Administered With Irinotecan (CPT-11) In Patients With Advanced Solid Tumors
- Determine the maximum tolerated dose of flavopiridol when combined with irinotecan in
patients with advanced solid tumors.
- Determine the clinical pharmacokinetics of this regimen, as well as the plasma levels
of the active metabolite SN-38 and metabolic product SN-38 glucuronide in these
- Determine, in a preliminary manner, the therapeutic activity of this regimen in these
- Determine the role of p21 relative to treatment response and apoptosis in these
patients treated with this regimen.
OUTLINE: This is a dose-escalation, open-label, non-randomized study of flavopiridol.
Patients receive irinotecan IV over 30 minutes followed 7 hours later by flavopiridol IV
over 1 hour on days 1, 8, 15, and 22. Treatment continues every 6 weeks for a minimum of 2
courses in the absence of disease progression or unacceptable toxicity. During the first
week of the second course, patients receive flavopiridol alone on day 1 and irinotecan alone
on day 2.
Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 or more
of 6 patients in the initial cohort experience dose limiting toxicity during the first
course of treatment. An additional 10 patients are treated at the MTD.
PROJECTED ACCRUAL: A total of 44-50 patients will be accrued for this study within 1 year.
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment
Gary K. Schwartz, MD
Memorial Sloan-Kettering Cancer Center
United States: Federal Government
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|