Doxorubicin Hydrochloride, Cyclophosphamide, Docetaxel, and S-1 Before Surgery in Treating Women With Stage II or Stage III Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, docetaxel, and S-1, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II trial is studying giving doxorubicin hydrochloride together with cyclophosphamide, docetaxel, and S-1 before surgery in treating women with stage II or stage III breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine the rate of pathologic complete response in women with previously untreated stage II or III breast cancer treated with neoadjuvant doxorubicin hydrochloride and cyclophosphamide followed by docetaxel and S1. Secondary Determine the safety and tolerability of this regimen in these patients. Determine the rate of overall radiologic response in these patients. Determine the rate of breast-conserving procedures in these patients. Determine the disease-free survival of these patients. Investigate the relevant pharmacogenomics and biomarker(s) which will be useful to predict any responses to the anticancer treatments. OUTLINE: Patients receive neoadjuvant doxorubicin hydrochloride IV and cyclophosphamide IV on day 1. Treatment repeats every 3 weeks for up to 4 courses. Patients then receive docetaxel IV over 1 hour on day 1 and oral S-1 on days 1-14. Treatment repeats every 3 weeks for 4 courses. Two to four weeks later, patients undergo surgery to remove the tumor (either breast-conserving procedures or mastectomy). Patients may then undergo radiotherapy and receive endocrine therapy.

Official Title
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Neoadjuvant Doxorubicin and Cyclophosphamide Followed by Docetaxel and S-1 in Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: cyclophosphamide
* Drug: docetaxel
* Drug: doxorubicin hydrochloride
* Drug: tegafur-gimeracil-oteracil potassium
* Procedure: neoadjuvant therapy
* Procedure: therapeutic conventional surgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed invasive primary breast cancer Clinical (radiologic) stage II or III disease No T4d disease No inflammatory breast cancer ErbB2-negative disease OR patient cannot receive trastuzumab treatment ErbB2-positive disease defined as either immunohistochemistry 3+, or FISH- or CISH-positive; immunohistochemistry 2+ is to be determined according to FISH or CISH results PATIENT CHARACTERISTICS: Mobile ECOG performance status 0-1 Normal cardiac function (LVEF > 50%) Hemoglobin ≥ 10.0 g/dL Absolute neutrophil count ≥ 1,500/μL Platelet count ≥ 10 x 10^4/μL Creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 50 mL/min Total bilirubin ≤ 1.5 times ULN AST/ALT ≤ 2.5 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Able to swallow tablet whole with water No prior motor or sensory neurotoxicity CTCAE ≥ grade 2 No other serious disease or medical condition No uncontrolled or serious cardiovascular disease, including any of the following: Myocardial infarction within the past 6 months New York Heart Association class III or IV heart failure Uncontrolled angina pectoris Clinically significant pericardial disease Cardiac amyloidosis No history of symptomatic or therapy-requiring cardiac arrhythmia CTCAE grade 3 (e.g., multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, uncontrolled atrial fibrillation) No asymptomatic sustained ventricular tachycardia History of atrial fibrillation or cardiac arrhythmia controlled by medication allowed No uncontrolled infection, unstable peptic ulcer, uncontrolled diabetes, or any other contraindication to corticosteroid administration No history of infection or any other serious medical event which may cause any functional injury in the affected patient and consequently, interfere with continuing the study treatment No history of hypersensitivity to taxanes, fluorouracil, or S-1 No significant gastrointestinal malfunction that will affect S-1 absorption No history of other cancer within the past 5 years except properly treated carcinoma in situ of the uterine cervix or basal cell or squamous cell carcinoma of the skin No severe psychological or neurological disorder or dementia that would preclude understanding of the informed consent No psychological, social, family, or geographical condition, or difficult circumstance that would preclude follow-up or compliance with the protocol PRIOR CONCURRENT THERAPY: No prior systemic treatment for this cancer (e.g., radiotherapy, chemotherapy, hormone therapy, or biological therapy) No prior preoperative topical treatments (e.g., incomplete surgery or radiotherapy) for this cancer No concurrent drug(s) that may potentially cause changes in the pharmacological activity of S-1 formulation, including any of the following: Allopurinol Phenytoin

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cyclophosphamide|nan|
|Drug: docetaxel|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: tegafur-gimeracil-oteracil potassium|nan|
|Procedure: neoadjuvant therapy|nan|
|Procedure: therapeutic conventional surgery|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of pathologic complete response |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability |  |  | 
| Rate of overall radiologic response |  |  | 
| Rate of breast-conserving procedure |  |  | 
| Disease-free survival |  |  | 
| Relevant pharmacogenomics and biomarker(s) which may be useful to predict any responses to the anticancer treatments |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II breast cancer, stage III breast cancer