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

Sponsor:	Washington University School of Medicine
Collaborators:	Novartis Pfizer
Information provided by:	Washington University School of Medicine
ClinicalTrials.gov Identifier:	NCT00242203

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: Zoledronic acid Drug: Placebo	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:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Bone Density Breast Cancer Cancer

Drug Information available for: Epirubicin hydrochloride Epirubicin Docetaxel Zoledronic acid

U.S. FDA Resources

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

Primary Outcome Measures:

The principal study endpoints are presence/absence of bone marrow micrometastases and bone marrow density at the radius, lumbar spine, femoral neck, femoral head and calcaneus. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Secondary endpoints are time from diagnosis to relapse, site of relapse, and quality of life. [ Time Frame: Patients followed until death. ] [ Designated as safety issue: No ]

Enrollment:	120
Study Start Date:	October 2002
Estimated Study Completion Date:	September 2007
Estimated Primary Completion Date:	September 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Patients assigned to the Zometa group will receive 4 mg IV as a 15-minute infusion every 3 weeks for a total of 17 doses. Neoadjuvant chemotherapy: 4 cycles of Epirubicin/Taxotere; Perform Surgery; Adjuvant Chemotherapy: 2 cycles of Epirubicin/Taxotere (Patients who are HER-2 neu positive will receive Trastuzumab 6 mg/kg q 3 wks for 1 year post surgery); Radiation Therapy, +/- Hormones	Drug: Zoledronic acid Patients assigned to the Zometa group will receive 4 mg IV as a 15-minute infusion every 3 weeks for a total of 17 doses.Neoadjuvant chemotherapy: 4 cycles of Epirubicin/Taxotere; Perform Surgery; Adjuvant Chemotherapy: 2 cycles of Epirubicin/Taxotere (Patients who are HER-2 neu positive will receive Trastuzumab 6 mg/kg q 3 wks for 1 year post surgery); Radiation Therapy, +/- Hormones
Placebo Comparator: 2 Placebo; Neoadjuvant chemotherapy: 4 cycles of Epirubicin/Taxotere; Perform Surgery; Adjuvant Chemotherapy: 2 cycles of Epirubicin/Taxotere (Patients who are HER-2 neu positive will receive Trastuzumab 6 mg/kg q 3 wks for 1 year post surgery); Radiation Therapy, +/- Hormones	Drug: Placebo Placebo; Neoadjuvant chemotherapy: 4 cycles of Epirubicin/Taxotere; Perform Surgery; Adjuvant Chemotherapy: 2 cycles of Epirubicin/Taxotere (Patients who are HER-2 neu positive will receive Trastuzumab 6 mg/kg q 3 wks for 1 year post surgery); Radiation Therapy, +/- Hormones

Arms

Assigned Interventions

Experimental: 1

Patients assigned to the Zometa group will receive 4 mg IV as a 15-minute infusion every 3 weeks for a total of 17 doses. Neoadjuvant chemotherapy: 4 cycles of Epirubicin/Taxotere; Perform Surgery; Adjuvant Chemotherapy: 2 cycles of Epirubicin/Taxotere (Patients who are HER-2 neu positive will receive Trastuzumab 6 mg/kg q 3 wks for 1 year post surgery); Radiation Therapy, +/- Hormones

Drug: Zoledronic acid

Patients assigned to the Zometa group will receive 4 mg IV as a 15-minute infusion every 3 weeks for a total of 17 doses.Neoadjuvant chemotherapy: 4 cycles of Epirubicin/Taxotere; Perform Surgery; Adjuvant Chemotherapy: 2 cycles of Epirubicin/Taxotere (Patients who are HER-2 neu positive will receive Trastuzumab 6 mg/kg q 3 wks for 1 year post surgery); Radiation Therapy, +/- Hormones

Placebo Comparator: 2

Placebo; Neoadjuvant chemotherapy: 4 cycles of Epirubicin/Taxotere; Perform Surgery; Adjuvant Chemotherapy: 2 cycles of Epirubicin/Taxotere (Patients who are HER-2 neu positive will receive Trastuzumab 6 mg/kg q 3 wks for 1 year post surgery); Radiation Therapy, +/- Hormones

Drug: Placebo

Placebo; Neoadjuvant chemotherapy: 4 cycles of Epirubicin/Taxotere; Perform Surgery; Adjuvant Chemotherapy: 2 cycles of Epirubicin/Taxotere (Patients who are HER-2 neu positive will receive Trastuzumab 6 mg/kg q 3 wks for 1 year post surgery); Radiation Therapy, +/- Hormones

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

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

Publications:

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Saarto T, Blomqvist C, Välimäki M, Mäkelä P, Sarna S, Elomaa I. Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy causes rapid bone loss that is reduced by clodronate: a randomized study in premenopausal breast cancer patients. J Clin Oncol. 1997 Apr;15(4):1341-7.

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Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Aft R, Naughton M, Trinkaus K, Watson M, Ylagan L, Chavez-MacGregor M, Zhai J, Kuo S, Shannon W, Diemer K, Herrmann V, Dietz J, Ali A, Ellis M, Weiss P, Eberlein T, Ma C, Fracasso PM, Zoberi I, Taylor M, Gillanders W, Pluard T, Mortimer J, Weilbaecher K. Effect of zoledronic acid on disseminated tumour cells in women with locally advanced breast cancer: an open label, randomised, phase 2 trial. Lancet Oncol. 2010 May;11(5):421-8. Epub 2010 Mar 31.

Responsible Party:	Rebecca Aft, MD, PhD, Washington University School of Medicine
ClinicalTrials.gov Identifier:	NCT00242203 History of Changes
Other Study ID Numbers:	02-0788
Study First Received:	October 17, 2005
Last Updated:	November 15, 2010
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:

Breast Cancer
Neoadjuvant
Micrometastasis

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Epirubicin
Zoledronic acid

Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Bone Density Conservation Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 21, 2012