Abraxane and Lapatinib in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT00331630
- Lead Sponsor
- Northwestern University
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment arm paclitaxel albumin-stabilized nanoparticle formulation 30 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. Treatment arm lapatinib ditosylate 30 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.
- Primary Outcome Measures
Name Time Method Clinical Response Rate (cRR) At Baseline, then before each treatment cycle begins and after 4 cycles of study treatment (1 cycle = 21 days) cRR measured by RECIST for target lesions assessed by clinical exam+ mammogram+ ultrasound (US). cRR is defined as number of patients who's best response in any of the assessments (clinical exam/mammogram/US) is CR+PR. Response will be defined as one of the following in either clinical exam, mammogram or US: Complete Response (CR)-Disappearance of all target lesions. Partial Response (PR)\>=30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum.
Stable Disease-neither sufficient shrinkage to qualify for Partial disease nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD while on study.
Progressive Disease \<=20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
- Secondary Outcome Measures
Name Time Method Angiogenesis (vW, CD34) Markers as Measured at Baseline and After Completion of Study Treatment At baseline, then after 4 cycles of study treatment (1 cycle = 21 days ) Angiogenesis (vW, CD34) markers will be assessed by breast biopsy at baseline and after 4 cycles of study treatment (1 cycle = 21 days). Expressions were analyzed by light microscopy in invasive breast cancer regions.
Tumor cells were assigned a score:
0 = no staining
1. weak staining less than 1% of tumor cells
2. = medium staining in 1-10% of tumor cells/weak staining in less than 1% of tumor cells
3. = medium or strong staining in more than 10% of the tumor cells. Capillary density was assessed in breast sections stained for CD34 at a x200 magnification by counting the number of capillaries per field with five fields per slide and results expressed as the average number of capillaries per field.Proliferation (Ki67) Measured at Baseline and After Completion of Study Treatment At baseline, then after 4 cycles of study treatment (1 cycle = 21 days ) Correlation of proliferation (Ki67) will be assessed by breast biopsy at baseline and after 4 cycles of study treatment (1 cycle = 21 days). Ki67 scoring was performed based on degree of staining (0= no staining, 1=weak nuclear staining, 2=moderate nuclear staining, 3=strong nuclear staining). Ki67 scores were counted on a maximum of 10 randomly selected x40 high-power fields with an eyepiece grid of 10x10 squares containing representative sections of tumor and calculated as percentage of positively stained cells to total tumor cells (Percent Score method) Ki67 labeling Index (LI) as assessed by counting a maximum of 1,000 malignant cells at x400 magnification.
Epidermal Growth Factor Receptor (EGFR), and Matrix Metalloproteinases (MMPs), Measured at Baseline and After Completion of Study Treatment At baseline, then after 4 cycles of study treatment (1 cycle = 21 days ) Epidermal growth factor receptor (EGFR), HER2/neu, matrix metalloproteinases (MMPs), and transforming growth factor (TGF-β) will be assessed by breast biopsy at baseline and after 4 cycles of study treatment (1 cycle = 21 days) with expressions analyzed by light microscopy in invasive breast cancer regions.
MMP2 cytoplasmic staining intensity was assigned a score:
0=no reactivity,
1. =1-10% of tumor cells reactive,
2. =11-25% of tumor cells reactive,
3. = 26-50% of cells reactive,
4. = more than 50% of cells reactive
Greater than or equal to 2+ score was considered positive for expression.
EGFR membrane staining was assigned a score:
0 = no staining or faint staining in less than 10% of cells
1. = faint incomplete membrane staining in more than 10% of cells
2. = weak to moderate complete membrane staining of more than 10% of cells
3. = strong complete membrane staining in more than 10% of tumor cellsPathologic Complete Response (pCR) At baseline, then after 4 cycles of study treatment (1 cycle = 21 days ) and at surgery Pathologic Complete Response (pCR) will be assessed by breast biopsy at baseline and after 4 cycles of study treatment (1 cycle = 21 days) and at surgery. This will be defined as the number of patients that show a pCR after surgery. pCR is defined as the absence of histologic evidence of invasive tumor cells in the surgical breast specimen and axillary lymph nodes.
Apoptosis (Cleaved Caspase-3) Measured at Baseline and After Completion of Study Treatment At baseline, then after 4 cycles of study treatment (1 cycle = 21 days ) Apoptosis/cleaved caspase-3 (CC3) will be assessed by breast biopsy at baseline and after 4 cycles of study treatment (1 cycle = 21 days). Scoring was based on the degree of staining (0=more than 90% of tumor cells with no staining, 1= more than 90% of tumor cells have weak staining, 2= more than 90% of tumor cells have moderate staining, 3= more than 90% of tumor cells have strong staining). CC3 scores were counted on a maximum of 10 randomly selected x40 high-power fields with an eyepiece grid of 10x10 squares containing representative sections of tumor and calculated as percentage of positively stained cells to total tumor cells (Percent Score method) CC3 labeling Index (LI) as assessed by counting a maximum of 1,000 malignant cells at x400 magnification.
Side Effects From the Combination of Abraxane and Lapatinib At baseline, then before the start of each study treatment cycle (1 cycle = 21 days) begins Side effects from the combination of Abraxane and Lapatinib will be assessed using CTCAE 3.0. Side effects that were related to study treatment and grade 3 or higher were collected where:
Grade 1= Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life-threatening Grade 5 = Death
Trial Locations
- Locations (5)
Northwestern University, Northwestern Medical Faculty Foundation
🇺🇸Chicago, Illinois, United States
Hematology-Oncology Associates of Illinois
🇺🇸Chicago, Illinois, United States
Midwest Center for Hematology/Oncology
🇺🇸Joliet, Illinois, United States
Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields
🇺🇸Olympia Fields, Illinois, United States
Joe Arrington Cancer Research and Treatment Center
🇺🇸Lubbock, Texas, United States