Docetaxel and Imatinib Mesylate in Treating Patients With Locally Advanced or Metastatic Breast Cancer

Breast Cancer Clinical Trial

Official title: A Phase I Study Of Weekly Taxotere (Docetaxel) And Gleevec (STI571, Imatinib Mesylate, CGP 57148B) In Locally Advanced Or Metastatic Breast Cancer

Status Completed

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy such as docetaxel work in different ways to stop tumor cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Giving docetaxel with imatinib mesylate may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of docetaxel when given together with imatinib mesylate in treating patients with locally advanced or metastatic breast cancer.

Clinical Trial Description

OBJECTIVES:

Primary

• 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.

Secondary

• 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. ;

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

• NCT number: NCT00080665
• Study type: Interventional
• Source: Sidney Kimmel Comprehensive Cancer Center
• Status: Completed
• Phase: Phase 1
• Start date: December 2003
• Completion date: January 2011