A Phase I Study Of Weekly Taxotere (Docetaxel) And Gleevec (STI571, Imatinib Mesylate, CGP 57148B) In Locally Advanced Or Metastatic Breast Cancer
- Determine the safety profile, maximum tolerated dose, and recommended phase II dose of
docetaxel when administered with imatinib mesylate in patients with locally advanced or
metastatic breast cancer.
- Determine the pharmacokinetic profile of this regimen in these patients.
- Determine the potential effects of this regimen on CYP3A4 activity and docetaxel
metabolism in these patients.
- Correlate docetaxel and imatinib mesylate exposure (utilizing total and unbound
docetaxel and imatinib mesylate plasma concentrations) with drug response (e.g.,
pharmacodynamic effects, drug toxicity, and response) in these patients.
- Determine response rate, duration of response, and time to treatment failure in
patients treated with this regimen.
- Correlate proteomic profile changes in serum with tumor burden and response in patients
treated with this regimen.
- Correlate pharmacokinetic parameters, tissue expression of specific receptor tyrosine
kinases (e.g., c-Kit, platelet-derived growth factor receptor [PDGFR], and
phosphorylated PDGFR) in paraffin blocks, and pharmacodynamic assays with antitumor
activity of this regimen in these patients.
OUTLINE: This is an open-label, dose-escalation study of docetaxel.
Patients receive docetaxel IV over 1 hour on days 1, 8, and 15 and oral imatinib mesylate
(STI571) on days 8-28 of course 1 and days 1-28 of all subsequent courses. Courses repeat
every 28 days in the absence of disease progression or unacceptable toxicity*. Patients with
stable or responding disease after at least 2 courses of therapy may discontinue docetaxel
and continue therapy with single-agent STI571 until disease progression.
NOTE: *Patients experiencing excessive docetaxel-related toxicity who have completed at
least 2 full courses may continue on single-agent STI571 in the absence of disease
progression or excessive STI571-related toxicity.
Cohorts of 3-6 patients receive escalating doses of docetaxel 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. An additional cohort of 6-12 patients
receives treatment at the MTD.
Patients are followed at 30 days.
PROJECTED ACCRUAL: Approximately of 18-30 patients will be accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
2.1.1 To determine the safety profile, maximum tolerated dose, and recommended dose for subsequent phase II studies of a combination regimen of daily STI571 with weekly docetaxel on days 1, 8, and 15 in a 28-day cycle.
Antonio C. Wolff, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Federal Government
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|