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| Name | Class |
|---|---|
| Novartis | INDUSTRY |
| Pfizer | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Zometa | Experimental | 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
Surgery - modified radical mastectomy or breast conserving surgery with axillary lymph node dissection Adjuvant therapy
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 | Active Comparator | Neoadjuvant therapy
Surgery - modified radical mastectomy or breast conserving surgery with axillary lymph node dissection Adjuvant therapy
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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zometa | Drug |
|
| |
| Epirubicin |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rebecca Aft, M.D., Ph.D. | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 8506892 | Background | 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. | |
| 9302893 | Background | 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. |
| Label | URL |
|---|---|
| Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine | View source |
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| Drug |
|
|
| Docetaxel | Drug |
|
|
| Trastuzumab | Drug | ONLY for patients that are Her-2 overexpressing by 3+ by ICH for FSH |
|
|
| External beam radiation | Radiation |
|
| Modified radical mastectomy or breast conserving surgery with axillary lymph node dissection | Procedure |
|
| 8970896 | Background | 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. |
| 10735906 | Background | 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. |
| 6690836 | Background | Cann CE, Martin MC, Genant HK, Jaffe RB. Decreased spinal mineral content in amenorrheic women. JAMA. 1984 Feb 3;251(5):626-9. |
| 11454877 | Background | 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. |
| 1148891 | Background | 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. |
| 1280141 | Background | 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. |
| 9330580 | Background | Reid IR. Glucocorticoid osteoporosis--mechanisms and management. Eur J Endocrinol. 1997 Sep;137(3):209-17. doi: 10.1530/eje.0.1370209. |
| Background | Van Staa T, Abenhaim L, Cooper C: Use of cyclic etidronate and prevention of fractures. Bone 20:103s (abstract), 1997 |
| 8950879 | Background | 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. |
| 11172164 | Background | 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. |
| 11870242 | Background | 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. |
| 9193325 | Background | 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. |
| 9060533 | Background | 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. |
| 10780527 | Background | 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. |
| 8833902 | Background | 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. |
| 10499498 | Background | 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. |
| 3745206 | Background | 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. |
| 3494250 | Background | 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. |
| Background | 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 |
| 9691109 | Background | 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. |
| 7627963 | Background | 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. |
| 8140935 | Background | 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. |
| 9153295 | Background | 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. |
| 10898341 | Background | 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. |
| 2961355 | Background | 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. |
| 8968035 | Background | 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. |
| 8823335 | Background | 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. |
| 38979716 | Derived | 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. |
| 33591469 | Derived | 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. |
| 20362507 | Derived | 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. |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D061206 | Neoplasm Micrometastasis |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D009362 | Neoplasm Metastasis |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000077211 | Zoledronic Acid |
| D015251 | Epirubicin |
| D000077143 | Docetaxel |
| D000068878 | Trastuzumab |
| D015411 | Mastectomy, Modified Radical |
| D015412 | Mastectomy, Segmental |
| ID | Term |
|---|---|
| D004164 | Diphosphonates |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D004317 | Doxorubicin |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D015409 | Mastectomy, Radical |
| D008408 | Mastectomy |
| D013514 | Surgical Procedures, Operative |
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