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

Phase 2

Completed

• Conditions: Breast Neoplasms
• Interventions: 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

• Registration Number: NCT00242203
• Lead Sponsor: Washington University School of Medicine

Brief Summary

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2002-10
• Study First Submitted: 2005-10-17
• Study First Submitted QC: 2005-10-17
• Study First Posted: 2005-10-19
• Primary Completion: 2007-08
• Study Completion: 2011-05
• Status Verified: 2013-08
• Last Update Submitted: 2013-08-09
• Last Update Posted: 2013-08-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 120

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Zometa	Zometa	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
Zometa	External beam radiation	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
Zometa	Modified radical mastectomy or breast conserving surgery with axillary lymph node dissection	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
No Zometa	External beam radiation	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
No Zometa	Modified radical mastectomy or breast conserving surgery with axillary lymph node dissection	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
Zometa	Trastuzumab	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
Zometa	Epirubicin	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
Zometa	Docetaxel	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
No Zometa	Trastuzumab	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
No Zometa	Docetaxel	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
No Zometa	Epirubicin	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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 St. Louis, Missouri, United States