Pilot Neoadjuvant Trial in Breast Cancer With Combination of ABI-007 (Abraxane) and GW572016 (Lapatinib)
Overview
- Phase
- Early Phase 1
- Intervention
- lapatinib ditosylate
- Conditions
- Breast Cancer
- Sponsor
- Northwestern University
- Enrollment
- 30
- Locations
- 5
- Primary Endpoint
- Clinical Response Rate (cRR)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment arm
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.
Intervention: lapatinib ditosylate
Treatment arm
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.
Intervention: paclitaxel albumin-stabilized nanoparticle formulation
Outcomes
Primary Outcomes
Clinical Response Rate (cRR)
Time Frame: 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 Outcomes
- 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 ))
- Proliferation (Ki67) 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), 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 ))
- Pathologic Complete Response (pCR)(At baseline, then after 4 cycles of study treatment (1 cycle = 21 days ) and at surgery)
- 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 ))
- 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)