Presurgical Therapy With Lapatinib to Explore Molecular Determinants of Response to EGFR/erbB2 Targeted Therapy

Study Overview
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Brief Summary
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The purpose of this study is to see what kinds of breast tumors will respond to lapatinib. Lapatinib is an experimental medicine which may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Lapatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically-confirmed by either core or fine needle biopsy primary invasive carcinoma of the breast; AJCC T2-T3 disease (>2.0 cm without chest wall or skin invasion) by at least one imaging modality (either mammogram, ultrasound, or MRI) - entry criteria is based on radiologic staging and not final pathologic staging; ECOG performance status 0-1 (Karnofsky ≥ 70% Any lymph node status, hormone receptor status, and level of erbB2 expression No prior chemotherapy, hormonal therapy or radiation therapy to the affected breast for current or previous malignancy; Cardiac ejection fraction >50% or within the institutional range of normal; Patients must have normal organ and marrow function defined as: Leukocyte count >3000/uL; Absolute neutrophil count (ANC) ≥ 1,500/mm3, platelets > 100,000/mm3, and hemoglobin ≥ 8 gm/dl; Serum creatinine ≤ 1.5 times ULN, or 24-hour creatinine clearance ≥ 75 cc/min; Serum bilirubin ≤ 1.5 times ULN; SGOT ≤ 2.5 times ULN; alkaline phosphatase ≤ 2.5 ULN times ULN. The effects of lapatinib 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 must inform her treating physician immediately. Ability to understand and the willingness to sign written informed consent document. Exclusion Criteria: AJCC T1, T4, or stage 4 disease; Patients may not have undergone incisional or excisional biopsy of their tumor; Patients may not be receiving any other investigational agents; Absolute contraindication to MRI imaging (cardiac pacemaker or any non-removable metallic foreign object in the body); On chronic therapy with any known inducer or inhibitor of CYP3A4 Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Pregnant or lactating women are excluded from this study because lapatinib is a tyrosine kinase inhibitor with the potential for teratogenic or abortifacient effects.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Lapatinib|Patients will take 14 days of Lapatinib prior to definitive surgery.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in downstream effector levels in biologic responders to lapatinib as determined by degree of change in proliferation and apoptosis compared to biologic non-responders. |  | Study completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To describe the biologic response rate, defined by induction of apoptosis, to Lapatinib in a pre-surgical, treatment-naïve breast cancer population. |  | Study completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Tyrosine kinase inhibitors, Lapatinib, Biologic response modifiers, Magnetic resonance imaging, Treatment-naive, operable