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

Sponsor

Washington University School of Medicine (Other)

Overall Status

Completed

CT.gov ID

NCT00242203

Collaborator

Novartis (Industry), Pfizer (Industry)

120

Enrollment

Location

Arms

103

Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms	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	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2002

Actual Primary Completion Date :

Aug 1, 2007

Actual Study Completion Date :

May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Zometa Other Names: Zoledronic acid Drug: Epirubicin Other Names: Ellence Drug: Docetaxel Other Names: Taxotere Drug: Trastuzumab ONLY for patients that are Her-2 overexpressing by 3+ by ICH for FSH Other Names: Herceptin Radiation: External beam radiation Procedure: Modified radical mastectomy or breast conserving surgery with axillary lymph node dissection
Active Comparator: No Zometa 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 Other Names: Ellence Drug: Docetaxel Other Names: Taxotere Drug: Trastuzumab ONLY for patients that are Her-2 overexpressing by 3+ by ICH for FSH Other Names: Herceptin Radiation: External beam radiation Procedure: Modified radical mastectomy or breast conserving surgery with axillary lymph node dissection

Arm

Intervention/Treatment

Experimental: 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

Drug: Zometa

Other Names:

Zoledronic acid

Drug: Epirubicin

Other Names:

Ellence

Drug: Docetaxel

Other Names:

Taxotere

Drug: Trastuzumab

ONLY for patients that are Her-2 overexpressing by 3+ by ICH for FSH

Other Names:

Herceptin

Radiation: External beam radiation

Procedure: Modified radical mastectomy or breast conserving surgery with axillary lymph node dissection

Active Comparator: No Zometa

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

Other Names:

Ellence

Drug: Docetaxel

Other Names:

Taxotere

Drug: Trastuzumab

ONLY for patients that are Her-2 overexpressing by 3+ by ICH for FSH

Other Names:

Herceptin

Radiation: External beam radiation

Procedure: Modified radical mastectomy or breast conserving surgery with axillary lymph node dissection

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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