This phase II trial is studying how well giving trastuzumab together with ixabepilone and carboplatin works in treating patients with HER2/neu-positive metastatic breast cancer. 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 ixabepilone and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining trastuzumab with ixabepilone and carboplatin may kill more tumor cells.
PRIMARY OBJECTIVES: I. To determine the response rate (as determined by RECIST criteria) to combination therapy with Ixabepilone (BMS-247550), trastuzumab, and carboplatin in patients with metastatic breast cancer known to overexpress HER2. SECONDARY OBJECTIVES: I. To determine time to disease progression (TTP) and time to treatment failure (TTF) after treatment with Ixabepilone (BMS-247550), trastuzumab and carboplatin in patients with metastatic breast cancer known to overexpress HER2. II. To determine the toxicity of combination therapy with Ixabepilone (BMS-247550), trastuzumab and carboplatin in patients with metastatic breast cancer known to overexpress HER2. III. To evaluate overall survival (OS) of combination therapy with Ixabepilone (BMS-247550), trastuzumab, and carboplatin in patients with metastatic breast cancer known to overexpress HER2. IV. To correlate levels of phospho-STAT3 with levels of HER2, Survivin and EGFR expression as measured in tissue by immunohistochemistry. OUTLINE: This is a multicenter study. Induction therapy: Patients receive trastuzumab (Herceptin®) IV over 30 minutes\* on days 1, 8, 15, and 22 and ixabepilone IV over 1 hour and carboplatin IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity. NOTE: \*Trastuzumab is given over 90 minutes on day 1 of course 1 (induction therapy) only. Maintenance therapy: Patients receive trastuzumab IV over 90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 3 years from study entry. PROJECTED ACCRUAL: A total of 10-60 patients will be accrued for this study within 1-6 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
61
Eastern Cooperative Oncology Group
Boston, Massachusetts, United States
Objective Response for HER2+ Patients (Best Objective Response a Patient Has Ever Experienced on Study)
To assess objective response, it is necessary to estimate the overall tumor burden at baseline to which subsequent measurements will be compared. The same method of assessment and the same technique should be used to characterize each lesion at baseline and during follow-up. The best overall response based on RECIST is the best response recorded from registration until disease progression/recurrence, taking as reference for progressive disease the smallest measurements recorded since registration. The best response was determined based on the tumor responses in target and nontarget lesions, with or without new lesions. To be assigned a status of complete or partial response, changes in tumor measurements must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met. To be assigned a status of stable disease, measurements must have met the stable disease criteria at least once after study entry at a minimum interval of 8 weeks.
Time frame: Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years
Objective Response for All Treated Patients (the Best Response a Patient Has Ever Experienced on Study)
To assess objective response, it is necessary to estimate the overall tumor burden at baseline to which subsequent measurements will be compared. The same method of assessment and the same technique should be used to characterize each lesion at baseline and during follow-up. The best overall response based on RECIST is the best response recorded from registration until disease progression/recurrence, taking as reference for progressive disease the smallest measurements recorded since registration. The best response was determined based on the tumor responses in target and nontarget lesions, with or without new lesions. To be assigned a status of complete or partial response, changes in tumor measurements must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met. To be assigned a status of stable disease, measurements must have met the stable disease criteria at least once after study entry at a minimum interval of 8 weeks.
Time frame: Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years
Time to Disease Progression for HER2+ Patients
This interval will be measured from the date of entry on the study to the appearance of new metastatic lesions or objective tumor progression based on RECIST. Patients progression-free at last follow-up were censored.
Time frame: Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years
Time to Disease Progression for All Treated Patients
This interval will be measured from the date of entry on the study to the appearance of new metastatic lesions or objective tumor progression based on RECIST. Patients progression-free at last follow-up were censored.
Time frame: Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years
Time to Treatment Failure for HER2+ Patients
Time from study entry to the date at which a patient was removed from treatment due to progression, toxicity, refusal or death. If a patient was considered to be a major treatment violation or was taken off study as a non-protocol failure, the patient would be censored on the date he/she was removed from treatment.
Time frame: Assessed every cycle until treatment discontinuation
Time to Treatment Failure for All Treated Patients
Time from study entry to the date at which a patient was removed from treatment due to progression, toxicity, refusal or death. If a patient was considered to be a major treatment violation or was taken off study as a non-protocol failure, the patient would be censored on the date he/she was removed from treatment.
Time frame: Assessed every cycle until treatment discontinuation
Kaplan-Meier Estimate of Overall Survival at 3 Years for HER2+ Patients
Survival estimate from the Kaplan-Meier curve of the proportion of patients alive at 3 years.
Time frame: Assessed every 3 months for 2 years, then every 6 months for 3 years
Kaplan-Meier Estimate of Overall Survival at 3 Years for All Treated Patients
Survival estimate from the Kaplan-Meier curve of the proportion of patients alive at 3 years.
Time frame: Assessed every 3 months for 2 years, then every 6 months for 3 years
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