Doxorubicin and Cyclophosphamide Followed by Paclitaxel, Trastuzumab, and Lapatinib in Treating Patients With HER2/Neu-Overexpressed Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to study a new treatment for HER-2/neu (+) breast cancer.

Official Title
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Phase II Study of Dose-Dense Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Paclitaxel With Trastuzumab and Lapatinib in HER2/NEU-Overexpressed/Amplified Breast Cancer: Feasibility

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: trastuzumab
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: lapatinib ditosylate
* Drug: paclitaxel
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the breast Bilateral synchronous breast tumors allowed Any nodal status or tumor size allowed No stage IV disease HER2/neu-positive disease 3+ by IHC OR FISH-amplified Hormone receptor status not specified PATIENT CHARACTERISTICS: Male or female Menopausal status not specified ECOG performance status 0-1 Absolute neutrophil count ≥ 1,000/mm³ Platelet count ≥ 100,000/mm³ Bilirubin ≤ 1.1 mg/dL SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and after completion of study therapy LVEF ≥ 50% by MUGA scan No peripheral neuropathy > grade 1 No active second malignancy within the past 5 years except for adequately treated nonmelanoma skin cancer or in situ carcinoma of the cervix No known allergy or hypersensitivity to doxorubicin hydrochloride, cyclophosphamide, paclitaxel, or other drugs formulated in Cremophor EL No psychiatric illness or concurrent medical conditions that would preclude study treatment No other conditions, including any of the following: Unstable angina Congestive heart failure Myocardial infarction within the past 12 months High-risk uncontrolled arrhythmias (e.g., ventricular tachycardia, high-grade AV block, or supraventricular arrhythmias that are not adequately controlled) No QT prolongation (> 500 ms) No active unresolved infections No sensitivity to E. coli derived proteins PRIOR CONCURRENT THERAPY: Prior hormonal therapy for chemoprevention allowed No prior trastuzumab (Herceptin®) No prior anthracyclines No concurrent hormonal therapy, including hormonal contraception (e.g., birth control pills or ovarian hormonal or replacement therapy) No other concurrent chemotherapy, radiotherapy, immunotherapy, or biotherapy for breast cancer No concurrent drugs that may prolong the QT

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AC, PACLITAXEL , TRASTUZUMAB & LAPATINIB<br>The regimen consists of AC (doxorubicin 60 mg/m2, cyclophosphamide 600 mg/m2) q 14 days x 4 with pegfilgrastim, followed by weekly paclitaxel (80 mg/m2) x 12 + trastuzumab (H) + lapatinib (L). Pegfilgrastim 6mg is given subcutaneously (SQ) on day # 2 of each AC. Filgrastim may be used in lieu of pegfilgrastim at the physician's discretion. Trastuzumab will be administered weekly starting with paclitaxel treatment # 1. Near the completion of all chemotherapy, patients may receive trastuzumab on a q 3-weekly schedule, starting as early as with paclitaxel cycle # 12. The total duration of trastuzumab from beginning to end is 52 weeks. Lapatinib will be given orally at 1000 mg daily, starting with trastuzumab for a total duration of 52 weeks. Hormonal therapy such as tamoxifen or an aromatase inhibitor will be given to patients with hormone receptor positive disease at the physician's discretion. Radiation therapy to the breast or chest is recommended to patients as appropriate. | Biological: trastuzumab<br> <br> Drug: cyclophosphamide<br> <br> Drug: doxorubicin hydrochloride<br> <br> Drug: lapatinib ditosylate<br> <br> Drug: paclitaxel<br> <br> Other: laboratory biomarker analysis<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Completed All Planned Therapy | The number of patients who completed all planned therapy (dose-dense adjuvant/ neoadjuvant chemotherapy regimen) in HER-2/neu-overexpressed/ amplified breast cancer patients. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Were Evaluated for Toxicity | Please see adverse event section in the results. Toxicities were assessed by the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent breast cancer, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, male breast cancer