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

This study has been completed.
Sponsor:
Collaborators:
Novartis
Pfizer
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00242203
First received: October 17, 2005
Last updated: August 9, 2013
Last verified: August 2013
  Purpose

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 Intervention 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 Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
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

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Evaluate the impact of Zometa (zoledronic acid) on the clearance of bone marrow micrometastases [ Time Frame: Prior to therapy initiation, after completion of neoadjuvant chemotherapy, and 12-15 months from registration ] [ Designated as safety issue: No ]
  • Evaluate the protective effect of Zometa (zoledronic acid) on chemotherapy-induced loss of bone mineral density [ Time Frame: Prior to therapy initiation and 12-15 months from registration ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Impact of Zometa (zoledronic acid) on time and site of relapse [ Time Frame: 5 years from registration ] [ Designated as safety issue: No ]
  • Effect of treatment on quality of life in women undergoing treatment for LABC. [ Time Frame: Baseline and 12-15 months from registration ] [ Designated as safety issue: No ]

Enrollment: 120
Study Start Date: October 2002
Study Completion Date: May 2011
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Zoledronic acid
Drug: Epirubicin
Other Name: Ellence
Drug: Docetaxel
Other Name: Taxotere
Drug: Trastuzumab
ONLY for patients that are Her-2 overexpressing by 3+ by ICH for FSH
Other Name: 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 Name: Ellence
Drug: Docetaxel
Other Name: Taxotere
Drug: Trastuzumab
ONLY for patients that are Her-2 overexpressing by 3+ by ICH for FSH
Other Name: Herceptin
Radiation: External beam radiation Procedure: Modified radical mastectomy or breast conserving surgery with axillary lymph node dissection

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00242203

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Novartis
Pfizer
Investigators
Principal Investigator: Rebecca Aft, M.D., Ph.D. Washington University School of Medicine
  More Information

Additional Information:
Publications:
Van Staa T, Abenhaim L, Cooper C: Use of cyclic etidronate and prevention of fractures. Bone 20:103s (abstract), 1997
Reid I, Brown J, Burckhardt P, et al: Intravenous zoledronic acid in postmenopausal women with low bone density. New England Journal of Medicine 346:653-661, 2002
Yin J, Chirgwin J, Taylor S: Dominant negative blockade of the transforming growth factor beta type II receptor decreases breast cancer mediated osteolysis. Journal of Bone and Mineral Research 11:180, 1996

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00242203     History of Changes
Other Study ID Numbers: 02-0788 / 201104272
Study First Received: October 17, 2005
Last Updated: August 9, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
Breast Cancer
Neoadjuvant
Micrometastasis

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Docetaxel
Epirubicin
Trastuzumab
Zoledronic acid
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Bone Density Conservation Agents
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Tubulin Modulators

ClinicalTrials.gov processed this record on October 23, 2014