Therapy With Docetaxel and ZD1839 for Patients Who Have Advanced Breast Cancer
The purpose of this study is to learn how breast cancer tumors respond to treatment combining the drugs docetaxel and ZD1839.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2, Multi-Center Trial of ZD1839 (IRESSA) in Combination With Docetaxel as First-Line Treatment in Patients With Advanced Breast Cancer|
- To estimate the clinical benefit rate of the combination of ZD 1839 and docetaxel; clinical benefit measured by clinical response, pathologic response, and stable disease (SD greater than or equal to 24 weeks) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To characterize the safety profile of the combination of ZD 1839 and docetaxel as measured by the frequency and severity of adverse events. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- To estimate the duration of clinical benefit. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To estimate the objective tumor response rate (using RECIST best overall response of CR + PR). [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To estimate the duration of tumor response. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To estimate progression-free survival. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To estimate time to treatment failure by measuring time to treatment failure (includes disease progression, second primary cancer, death from any cause, or discontinuation of protocol therapy in the absence of disease progression). [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||January 2003|
|Study Completion Date:||September 2006|
Drug: ZD1839 in combination with docetaxel
- Docetaxel (Taxotere)
- ZD1839, gefitinib (Iressa)
Patients with advanced breast cancer continue to have an extremely poor prognosis with an average life expectancy of approximately 2 years. Novel treatments designed to exploit biologic properties of the tumor are urgently required as a means to improve the outcome for the large numbers of patients who relapse after receiving optimal chemotherapy treatments.
Overexpresssion of EGFR and/or TGF-alpha is frequent in human breast cancer and has been correlated in many cases with poor prognostic features. Inhibition of the EGFR pathway has been proposed as a potential therapeutic modality in advanced breast cancer. The antiproliferative activity of ZD 1839 in combination with cytotoxic drugs, such as docetaxel was evaluated in breast cancer cell lines ZR-75-1 and MCF-10A ras that coexpress EGFR and TGF-alpha. Combination treatment demonstrated dose dependent supra-additive growth inhibition and markedly enhanced apoptotic cell death.
Although taxanes bind to the microtubular network in cells that is essential for mitotic and interphase cellular functions, the mechanism by which these agents induce cell death is not entirely clear. Docetaxel has also shown dose-dependent anti-angiogenic activity. Thus, the mechanism(s) of anti-tumor activity of docetaxel remain unclear and combinations of signal transduction pathway inhibition and/or anti-angiogenesis may provide potentiation of concurrent ZD 1839 and docetaxel therapy.
This phase 2 trial is designed to prospectively investigate the efficacy and safetey of combination therapy with ZD 1839 and docetaxel in patients with metastatic breast cancer.
|United States, Pennsylvania|
|NSABP Operations Center|
|Pittsburgh, Pennsylvania, United States, 15212|
|Principal Investigator:||Norman Wolmark, MD||NSABP Foundation, Inc.|