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About
This phase II trial is studying how well giving trastuzumab together with ixabepilone works in treating women with HER2-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, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining trastuzumab with ixabepilone may kill more tumor cells.
Full description
PRIMARY OBJECTIVES:
I. Examine the response rate of HER2-positive metastatic breast cancer to combination therapy with trastuzumab and BMS-247550 in two cohorts of women: a. women who have received no prior chemotherapy or trastuzumab for their metastatic breast cancer; b. women who have received prior trastuzumab therapy (either for metastatic disease or prior adjuvant trastuzumab if < 1 year since completion of adjuvant trastuzumab therapy) and up to 2 prior chemotherapeutic regimens in the metastatic setting.
SECONDARY OBJECTIVES:
I. To characterize the safety and toxicity profile of trastuzumab in combination with BMS-247550.
II. To determine the time-to-disease-progression (TTP) and time-to-treatment-failure (TTF) for patients receiving trastuzumab in combination with BMS-247550 in each cohort.
III. Analyze various tissue biomarkers (e.g. HER2/phospho-HER2, EGFR/phospho-EGFR, IGRF-I, phospho-MAPK, phospho-P13K, bcl-2, bcl-xL, MDR-1, MRP and β-tubulin) and blood biomarkers (HER2-extracellular domain [ECD], circulating tumor cells) to correlate them with response to treatment.
OUTLINE: This is an open-label, multicenter study. Patients are stratified according to prior trastuzumab (Herceptin®) therapy (with or without chemotherapy) for metastatic breast cancer (yes vs no).
Patients receive trastuzumab IV over 30-90 minutes and ixabepilone IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
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Inclusion criteria
Patients must have histologically or cytologically confirmed invasive breast cancer, with stage IV disease
Tumors must be HER2 overexpressing; acceptable methods of measurement of HER2 expression include immunohistochemistry IHC) and fluorescence in situ hybridization (FISH); tumors tested by IHC must be 3+ positive for HER2 overexpression; tumors tested by FISH must be positive by the specific FISH assay for genetic amplification of HER2; tumors that are 3+ by IHC, but negative by FISH assay are ineligible; consideration should be given to performing a repeat biopsy, with reanalysis for HER2 overexpression, in patients who have received prior trastuzumab, as little data exist on the persistence of HER2 overexpression after prior treatment with trastuzumab; biopsy in this circumstance, however, is not required
Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan; the protocol will employ the RECIST criteria
Prior Therapy - Two cohorts of patients will be treated on this treatment regimen; the two cohorts are determined by prior therapy and are as follows:
Treatment Cohort 1:
Treatment Cohort 2:
Life expectancy of greater than 6 months
ECOG performance status =< 2 (Karnofsky >= 60%)
Patients must have adequate organ and marrow function as defined below; laboratory tests should be completed within 14 days prior to registration; left ventricular ejection fraction (LVEF) may be determined by either echocardiography or nuclear scintigraphy (i.e. MUGA scan or RVG), and should be obtained within 28 days prior to registration
Absolute neutrophil count >= 1,500/mm^3
Platelets >= 100,000/mm^3
Total bilirubin =< 1.5 X institutional upper limit of normal
ALT(SGPT) =< 5 X institutional upper limit of normal
LVEF >= 50%
Concurrent Therapy: patients may not receive concurrent hormonal therapy, chemotherapy, or radiation treatments while on study; patients requiring radiation therapy during protocol-based treatment will be taken off study; if patients develop intraparenchymal brain metastases while on treatment, but do not have evidence of other systemic progression, they will be allowed to resume treatment with the combination once their radiation has been completed; they will be allowed to continue trastuzumab therapy during radiation, at the treating physician's discretion; nevertheless, the date of discovery of the CNS disease will still be considered the date of disease progression; patients may receive concurrent bisphosphonate therapy (e.g. pamidronate) while on study; patients may not receive other experimental treatments while on study
The effects of BMS-247550 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Ability to understand and the willingness to sign a written informed consent document
Patient Registration and Data Submission: Patients will be registered by contacting and faxing the completed eligibility checklist and all pages of the consent form to the Quality Assurance Office of Clinical Trials (QACT) at the Dana-Farber Cancer Institute; please fax to 617-632-2295 or telephone at 617-632-3761; a research nurse, Kathryn Clarke, will be available at 617-632-3478 to answer any protocol-related questions; you many also contact the study coordinator, Keri Hannagan, at 617-632-5584
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39 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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