Evaluation of Chemotherapy Prior to Surgery With or Without Zometa for Women With Locally Advanced Breast Cancer
NCT ID: NCT00242203
Last Updated: 2013-08-13
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
120 participants
INTERVENTIONAL
2002-10-31
2011-05-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
SINGLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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
Epirubicin
Docetaxel
Trastuzumab
ONLY for patients that are Her-2 overexpressing by 3+ by ICH for FSH
External beam radiation
Modified radical mastectomy or breast conserving surgery with axillary lymph node dissection
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
Epirubicin
Docetaxel
Trastuzumab
ONLY for patients that are Her-2 overexpressing by 3+ by ICH for FSH
External beam radiation
Modified radical mastectomy or breast conserving surgery with axillary lymph node dissection
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Zometa
Epirubicin
Docetaxel
Trastuzumab
ONLY for patients that are Her-2 overexpressing by 3+ by ICH for FSH
External beam radiation
Modified radical mastectomy or breast conserving surgery with axillary lymph node dissection
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
* 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
18 Years
FEMALE
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Novartis
INDUSTRY
Pfizer
INDUSTRY
Washington University School of Medicine
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Rebecca Aft, M.D., Ph.D.
Role: PRINCIPAL_INVESTIGATOR
Washington University School of Medicine
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Washington University School of Medicine
St Louis, Missouri, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med. 1993 Jun;94(6):646-50. doi: 10.1016/0002-9343(93)90218-e. No abstract available.
Cooper C. The crippling consequences of fractures and their impact on quality of life. Am J Med. 1997 Aug 18;103(2A):12S-17S; discussion 17S-19S. doi: 10.1016/s0002-9343(97)90022-x.
Schurch MA, Rizzoli R, Mermillod B, Vasey H, Michel JP, Bonjour JP. A prospective study on socioeconomic aspects of fracture of the proximal femur. J Bone Miner Res. 1996 Dec;11(12):1935-42. doi: 10.1002/jbmr.5650111215.
Pfeilschifter J, Diel IJ. Osteoporosis due to cancer treatment: pathogenesis and management. J Clin Oncol. 2000 Apr;18(7):1570-93. doi: 10.1200/JCO.2000.18.7.1570.
Cann CE, Martin MC, Genant HK, Jaffe RB. Decreased spinal mineral content in amenorrheic women. JAMA. 1984 Feb 3;251(5):626-9.
Shapiro CL, Manola J, Leboff M. Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss in women with early-stage breast cancer. J Clin Oncol. 2001 Jul 15;19(14):3306-11. doi: 10.1200/JCO.2001.19.14.3306.
Young DM, Fioravanti JL, Olson HM, Prieur DJ. Chemical and morphologic alterations of rabbit bone induced by adriamycin. Calcif Tissue Res. 1975 Jul 4;18(1):47-63. doi: 10.1007/BF02546226.
Glackin CA, Murray EJ, Murray SS. Doxorubicin inhibits differentiation and enhances expression of the helix-loop-helix genes Id and mTwi in mouse osteoblastic cells. Biochem Int. 1992 Oct;28(1):67-75.
Reid IR. Glucocorticoid osteoporosis--mechanisms and management. Eur J Endocrinol. 1997 Sep;137(3):209-17. doi: 10.1530/eje.0.1370209.
Van Staa T, Abenhaim L, Cooper C: Use of cyclic etidronate and prevention of fractures. Bone 20:103s (abstract), 1997
Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet. 1996 Dec 7;348(9041):1535-41. doi: 10.1016/s0140-6736(96)07088-2.
McClung MR, Geusens P, Miller PD, Zippel H, Bensen WG, Roux C, Adami S, Fogelman I, Diamond T, Eastell R, Meunier PJ, Reginster JY; Hip Intervention Program Study Group. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med. 2001 Feb 1;344(5):333-40. doi: 10.1056/NEJM200102013440503.
Reid IR, Brown JP, Burckhardt P, Horowitz Z, Richardson P, Trechsel U, Widmer A, Devogelaer JP, Kaufman JM, Jaeger P, Body JJ, Brandi ML, Broell J, Di Micco R, Genazzani AR, Felsenberg D, Happ J, Hooper MJ, Ittner J, Leb G, Mallmin H, Murray T, Ortolani S, Rubinacci A, Saaf M, Samsioe G, Verbruggen L, Meunier PJ. Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med. 2002 Feb 28;346(9):653-61. doi: 10.1056/NEJMoa011807.
Saarto T, Blomqvist C, Valimaki M, Makela 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. doi: 10.1200/JCO.1997.15.4.1341.
Delmas PD, Balena R, Confravreux E, Hardouin C, Hardy P, Bremond A. Bisphosphonate risedronate prevents bone loss in women with artificial menopause due to chemotherapy of breast cancer: a double-blind, placebo-controlled study. J Clin Oncol. 1997 Mar;15(3):955-62. doi: 10.1200/JCO.1997.15.3.955.
Senaratne SG, Pirianov G, Mansi JL, Arnett TR, Colston KW. Bisphosphonates induce apoptosis in human breast cancer cell lines. Br J Cancer. 2000 Apr;82(8):1459-68. doi: 10.1054/bjoc.1999.1131.
Guise TA, Yin JJ, Taylor SD, Kumagai Y, Dallas M, Boyce BF, Yoneda T, Mundy GR. Evidence for a causal role of parathyroid hormone-related protein in the pathogenesis of human breast cancer-mediated osteolysis. J Clin Invest. 1996 Oct 1;98(7):1544-9. doi: 10.1172/JCI118947.
Thomas RJ, Guise TA, Yin JJ, Elliott J, Horwood NJ, Martin TJ, Gillespie MT. Breast cancer cells interact with osteoblasts to support osteoclast formation. Endocrinology. 1999 Oct;140(10):4451-8. doi: 10.1210/endo.140.10.7037.
Hauschka PV, Mavrakos AE, Iafrati MD, Doleman SE, Klagsbrun M. Growth factors in bone matrix. Isolation of multiple types by affinity chromatography on heparin-Sepharose. J Biol Chem. 1986 Sep 25;261(27):12665-74.
Pfeilschifter J, Mundy GR. Modulation of type beta transforming growth factor activity in bone cultures by osteotropic hormones. Proc Natl Acad Sci U S A. 1987 Apr;84(7):2024-8. doi: 10.1073/pnas.84.7.2024.
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
Mundy GR, Yoneda T. Bisphosphonates as anticancer drugs. N Engl J Med. 1998 Aug 6;339(6):398-400. doi: 10.1056/NEJM199808063390609. No abstract available.
Sasaki A, Boyce BF, Story B, Wright KR, Chapman M, Boyce R, Mundy GR, Yoneda T. Bisphosphonate risedronate reduces metastatic human breast cancer burden in bone in nude mice. Cancer Res. 1995 Aug 15;55(16):3551-7.
Hall DG, Stoica G. Effect of the bisphosphonate risedronate on bone metastases in a rat mammary adenocarcinoma model system. J Bone Miner Res. 1994 Feb;9(2):221-30. doi: 10.1002/jbmr.5650090211.
Yoneda T, Sasaki A, Dunstan C, Williams PJ, Bauss F, De Clerck YA, Mundy GR. Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2. J Clin Invest. 1997 May 15;99(10):2509-17. doi: 10.1172/JCI119435.
Yoneda T, Michigami T, Yi B, Williams PJ, Niewolna M, Hiraga T. Actions of bisphosphonate on bone metastasis in animal models of breast carcinoma. Cancer. 2000 Jun 15;88(12 Suppl):2979-88. doi: 10.1002/1097-0142(20000615)88:12+3.0.co;2-u.
Elomaa I, Blomqvist C, Porkka L, Lamberg-Allardt C, Borgstrom GH. Treatment of skeletal disease in breast cancer: a controlled clodronate trial. Bone. 1987;8 Suppl 1:S53-6.
Kanis JA, Powles T, Paterson AH, McCloskey EV, Ashley S. Clodronate decreases the frequency of skeletal metastases in women with breast cancer. Bone. 1996 Dec;19(6):663-7. doi: 10.1016/s8756-3282(96)00285-2.
Conte PF, Latreille J, Mauriac L, Calabresi F, Santos R, Campos D, Bonneterre J, Francini G, Ford JM. Delay in progression of bone metastases in breast cancer patients treated with intravenous pamidronate: results from a multinational randomized controlled trial. The Aredia Multinational Cooperative Group. J Clin Oncol. 1996 Sep;14(9):2552-9. doi: 10.1200/JCO.1996.14.9.2552.
Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.
Jallouk AP, Paravastu S, Weilbaecher K, Aft RL. Long-term outcome of (neo)adjuvant zoledronic acid therapy in locally advanced breast cancer. Breast Cancer Res Treat. 2021 May;187(1):135-144. doi: 10.1007/s10549-021-06100-2. Epub 2021 Feb 16.
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. doi: 10.1016/S1470-2045(10)70054-1. Epub 2010 Mar 31.
Related Links
Access external resources that provide additional context or updates about the study.
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
02-0788 / 201104272
Identifier Type: -
Identifier Source: org_study_id