RATIONALE: Drugs used in chemotherapy, such as Abraxane, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. Giving Abraxane together with lapatinib may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving Abraxane together with lapatinib works in treating patients with stage I, stage II, or stage III breast cancer.
Primary Outcome Measures:
- Clinical response rate as measured by clinical exam and imaging studies [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Pathologic complete response rate [ Designated as safety issue: No ]
- Correlation of proliferation (Ki67) with tumor response as measured at baseline and after completion of study treatment [ Designated as safety issue: No ]
- Correlation of apoptosis (cleaved caspase-3) with tumor response as measured at baseline and after completion of study treatment [ Designated as safety issue: No ]
- Correlation of angiogenesis (vW, CD34) markers with tumor response as measured at baseline and after completion of study treatment [ Designated as safety issue: No ]
- Correlation of other studies with tumor response, including epidermal growth factor receptor (EGFR), HER2/neu, matrix metalloproteinases (MMPs), and transforming growth factor (TGF-β) as measured at baseline and after completion of study treatment [ Designated as safety issue: No ]
- Toxicity as measured by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
| Estimated Enrollment: |
30 |
| Study Start Date: |
May 2006 |
| Estimated Primary Completion Date: |
May 2011 (Final data collection date for primary outcome measure) |
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Group 1: Experimental
The first 10 patients receive Abraxane IV over 30 minutes on day 1 and oral lapatinib once daily on days 1-21. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
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Drug: lapatinib ditosylate
Given orally
Drug: paclitaxel albumin-stabilized nanoparticle formulation
Given IV
|
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Group 2: Experimental
The next 20 patients receive Abraxane and lapatinib (at a higher dose) as in group 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
|
Drug: lapatinib ditosylate
Given orally
Drug: paclitaxel albumin-stabilized nanoparticle formulation
Given IV
|
OBJECTIVES:
Primary
- Determine the clinical response rate, as measured by clinical exam and imaging studies, in patients with stage I-III breast cancer treated with neoadjuvant Abraxane in combination with lapatinib.
Secondary
- Determine the pathologic complete response rate in patients treated with this regimen.
- Correlate proliferation (Ki67), apoptosis (cleaved caspase-3), and angiogenesis (vW, CD34) markers, measured before and after treatment, with tumor response in these patients.
- Conduct other correlative studies, including epidermal growth factor receptor (EGFR), HER2/neu, matrix metalloproteinases (MMPs), and transforming growth factor (TGF-β), before and after treatment with this regimen to assess tumor response in these patients.
- Determine the toxicity of this regimen in these patients.
OUTLINE: This is a pilot study. Patients are assigned to 1 of 2 treatment groups.
- Group 1: The first 10 patients receive Abraxane IV over 30 minutes on day 1 and oral lapatinib once daily on days 1-21. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
- Group 2: The next 20 patients receive Abraxane and lapatinib (at a higher dose) as in group 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection and tumor biopsies periodically for correlative biomarker studies.
PROJECTED ACCRUAL: A total of 30 patients will be accrued to this study.
Purpose
