RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining gefitinib and trastuzumab with docetaxel may kill more tumor cells. PURPOSE: This phase I/II trial is studying the best dose of docetaxel when given together with gefitinib and trastuzumab in treating patients with metastatic breast cancer.
Name: trastuzumab
Description: Cycle 1 loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks for subsequent cycles.Type: BiologicalZD1839, Trastuzumab and Docetaxel
Name: docetaxel
Description: 75 mg/m2 every three weeks, or 60 mg/m2 every three weeks depending on study findingsType: DrugZD1839, Trastuzumab and Docetaxel
Name: gefitinib
Description: 250 mg daily or 250 mg daily on days 2 through 14 depending on study findingsType: DrugZD1839, Trastuzumab and Docetaxel
Description: Dose Limiting Toxicity (DLT) defined as any treatment-related grade 3 or greater except for hematological toxicities which must be grade 4. Interstitial Lung Disease (ILD) related to treatment should be considered as a DLT regardless of the grade.
Measure: Number of Participants With at Least One Dose Limiting Toxicity in Phase I Time: 4 weeks from start of treatment, up to 2 yearsDescription: The maximum tolerated dose (MTD): subjects received gefitinib 250 mg orally daily, trastuzumab 6 mg/kg intravenously every 3 weeks (after an initial dose of 8 mg/kg with cycle 1), and docetaxel 75 mg/m^2 intravenously every 3 weeks. This was to serve as the phase II dose if no dose-limiting toxicities (DLTs) occurred in the first three subjects. If one DLT occurred in the first three subjects, another three subjects where to be enrolled at this dose, whereas if two DLTs occurred in the first three subjects, the docetaxel dose was to be decreased to 60 mg/m^2. The study would then be continued only if no more than one patient had a DLT at this dose. Once the dose of docetaxel was established, all further subjects were to be treated at the phase II MTD dose.
Measure: Recommended Phase II Dose Time: 4 weeks from start of treatment, up to 2 yearsDescription: Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or the appearance of new lesions.
Measure: Progression-free Survival Time: Until disease progression, up to 5 years.Description: Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response Rate defined as percentage of patients achieving a Best Response of either CR or PR.
Measure: Objective Response Rate Time: After 3 cycles of treatment, up to 2 years.Description: Estimated using the product-limit method of Kaplan and Meier.
Measure: Overall Survival Time: Until death from any cause, up to 5 years.Single Group Assignment
There is one SNP
- Correlate expression and/or degree of phosphorylation of epidermal growth factor receptor, HER2/neu, c-fos, Akt, ERK½, P13K, p53, p21, and p27 with outcome in patients treated with this regimen. --- P13K ---