Evaluation of Chemotherapy Prior to Surgery With or Without Zometa for Women With Locally Advanced Breast Cancer

Study Overview
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Brief Summary
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This study is designed to evaluate the impact of Zometa on clearance of bone marrow micrometastases; the protective effect on chemotherapy-induced loss of bone mineral density; and quality of life in women undergoing treatment for locally advanced breast cancer.

Official Title
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Impact of Neoadjuvant Chemotherapy With or Without Zometa on Occult Micrometastases and Bone Density in Women With Locally Advanced Breast Cancer

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Drug: Zometa
* Drug: Epirubicin
* Drug: Docetaxel
* Drug: Trastuzumab
* Radiation: External beam radiation
* Procedure: Modified radical mastectomy or breast conserving surgery with axillary lymph node dissection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed primary invasive ductal or invasive lobular breast adenocarcinoma Tumor classified as clinically large T2 (2-5 cm), T3, T4 or any T with N1, N2 Prior malignancies: limited to curatively treated basal or squamous carcinoma of the skin or history of previous malignancies, treated and now > 5 years disease free >= 18 years of age Normal left ventricular function by echocardiogram or radioventriculogram Karnofsky Performance >= 70 Exclusion Criteria: No evidence of distant metastasis present by CT, Bone scan, or physical exam If the bone scan or CT scans demonstrate indeterminate lesions, the nature of these lesions may be further clarified by additional testing such as PET or MRI No current treatment with Zometa or other bisphosphonates No serious functional disorders of the liver or kidneys: Serum Creatinine <=2 ALT/AST/ALK Phos <= 1.5 x upper limit of institutional normal. Bili <= 1.5 x upper limit of institutional normal. Currently not pregnant

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: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zometa<br>Zometa 4 mg IV every 3 weeks for a total of 17 doses. The first treatment will be given at the time of the first chemotherapy treatment and will continue for approximately 1 year. Neoadjuvant therapy Epirubicin 75 mg/m2 IV every 21 days for 4 cycles prior to surgery Docetaxel 75 mg/m2 IV every 21 days for 4 cycles prior to surgery Surgery - modified radical mastectomy or breast conserving surgery with axillary lymph node dissection Adjuvant therapy Epirubicin 75 mg/m2 IV every 21 days for 2 cycles Docetaxel 75 mg/m2 IV every 21 days for 2 cycles All patients who are found to be Her-2 overexpressing by 3+ by ICH for FSH will receive trastuzumab 6 mg/kg IV every 3 weeks for 1 year post surgery Radiation therapy - 50-60 Gy in 1.8-2.0 Gy daily fractions to the breast or chest wall. Internal mammary nodes, supraclavicular fossa nodes and axillary nodal basins will receive 45-50 Gy over 5-6 weeks | Drug: Zometa<br> <br> * Other names: Zoledronic acid;Drug: Epirubicin<br> <br> * Other names: Ellence;Drug: Docetaxel<br> <br> * Other names: Taxotere;Drug: Trastuzumab<br>* ONLY for patients that are Her-2 overexpressing by 3+ by ICH for FSH<br>* Other names: Herceptin;Radiation: External beam radiation<br> <br> Procedure: Modified radical mastectomy or breast conserving surgery with axillary lymph node dissection<br> <br> |
| Active Comparator: No Zometa<br>Neoadjuvant therapy Epirubicin 75 mg/m2 IV every 21 days for 4 cycles prior to surgery Docetaxel 75 mg/m2 IV every 21 days for 4 cycles prior to surgery Surgery - modified radical mastectomy or breast conserving surgery with axillary lymph node dissection Adjuvant therapy Epirubicin 75 mg/m2 IV every 21 days for 2 cycles Docetaxel 75 mg/m2 IV every 21 days for 2 cycles All patients who are found to be Her-2 overexpressing by 3+ by ICH for FSH will receive trastuzumab 6 mg/kg IV every 3 weeks for 1 year post surgery Radiation therapy - 50-60 Gy in 1.8-2.0 Gy daily fractions to the breast or chest wall. Internal mammary nodes, supraclavicular fossa nodes and axillary nodal basins will receive 45-50 Gy over 5-6 weeks | Drug: Epirubicin<br> <br> * Other names: Ellence;Drug: Docetaxel<br> <br> * Other names: Taxotere;Drug: Trastuzumab<br>* ONLY for patients that are Her-2 overexpressing by 3+ by ICH for FSH<br>* Other names: Herceptin;Radiation: External beam radiation<br> <br> Procedure: Modified radical mastectomy or breast conserving surgery with axillary lymph node dissection<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the impact of Zometa (zoledronic acid) on the clearance of bone marrow micrometastases |  | Prior to therapy initiation, after completion of neoadjuvant chemotherapy, and 12-15 months from registration | 
| Evaluate the protective effect of Zometa (zoledronic acid) on chemotherapy-induced loss of bone mineral density |  | Prior to therapy initiation and 12-15 months from registration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of Zometa (zoledronic acid) on time and site of relapse |  | 5 years from registration | 
| Effect of treatment on quality of life in women undergoing treatment for LABC. |  | Baseline and 12-15 months from registration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Neoadjuvant, Micrometastasis