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Phase III Randomized Study of Doxorubicin Plus Cyclophosphamide Followed By Paclitaxel With or Without Trastuzumab (Herceptin®) in Women With HER-2-Overexpressing Node-Positive or High-Risk Node-Negative Breast Cancer
Alternate Title Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer
Objectives Primary
Secondary
Tertiary
Entry Criteria Disease Characteristics:
Prior/Concurrent Therapy: Biologic therapy:
Chemotherapy:
Endocrine therapy:
Radiotherapy:
Surgery:
Other:
Patient Characteristics: Age:
Sex:
Menopausal status:
Performance status:
Life expectancy:
Hematopoietic:
Hepatic:
Renal:
Cardiovascular:
Other:
Expected Enrollment A total of 3,700 patients (at least 1,150 for arms I and II and at least 1,000 for arm III) will be accrued for this study within approximately 5.75 years. Outline This is a randomized, multicenter study. Patients are stratified according to nodal status (0 vs 1-3 positive nodes by axillary nodal dissection vs 4-9 positive nodes by axillary nodal dissection vs at least 10 positive nodes by axillary nodal dissection vs positive sentinel node with no or negative axillary nodal dissection vs negative sentinel node with no axillary nodal dissection vs node negative by axillary nodal dissection) and receptor status (estrogen receptor [ER] or progesterone receptor [PR] positive vs other). Patients are randomized to 1 of 3 treatment arms.
Within 5 weeks after completion of paclitaxel, patients may undergo radiotherapy. All postmenopausal ER- or PR-positive patients receive oral tamoxifen or an aromatase inhibitor once daily for 5 years beginning no later than 5 weeks after the last dose of paclitaxel. Patients may also receive an aromatase inhibitor once daily for 5 years after 5 years of daily tamoxifen. Patients who receive tamoxifen once daily for less than 4.5 years may receive an aromatase inhibitor daily until they have received a total of 5 years of adjuvant hormonal therapy. Patients are followed every 3 months for 1 year, every 6 months for 4 years, and then annually for 15 years or until disease progression. Published ResultsHalyard MY, Pisansky TM, Dueck AC, et al.: Radiotherapy and Adjuvant Trastuzumab in Operable Breast Cancer: Tolerability and Adverse Event Data From the NCCTG Phase III Trial N9831. J Clin Oncol : , 2009.[PUBMED Abstract] Moreno-Aspitia A, Dueck AC, Lingle WL, et al.: Serum HER2 (sHER2) levels in early-stage HER2 neu (+) breast cancer (HER2+BC): results from the NCCTG adjuvant Intergroup trial N9831. [Abstract] J Clin Oncol 26 (Suppl 15): A-529, 2008. Perez EA, Reinholz MM, Dueck AC, et al.: c-MYC amplification and correlation with patient outcome in early stage HER2+ breast cancer from the NCCTG adjuvant intergroup trial N9831. [Abstract] 31st Annual San Antonio Breast Cancer Symposium, December 10-14, 2008, San Antonio, Texas. A-56, 2008. Perez EA, Suman VJ, Davidson NE, et al.: Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial. J Clin Oncol 26 (8): 1231-8, 2008.[PUBMED Abstract] Kutteh LA, Hobday T, Jaffe A, et al.: A correlative study of cardiac biomarkers and left ventricular ejection fraction (LVEF) from N9831, a phase III randomized trial of chemotherapy and trastuzumab as adjuvant therapy for HER2-positive breast cancer. [Abstract] J Clin Oncol 25 (Suppl 18): A-579, 2007. Reinholz MM, Jenkins RB, Hillman D, et al.: The clinical significance of polysomy 17 in the HER2+ N9831 intergroup adjuvant trastuzumab trial. [Abstract] Breast Cancer Res Treat 106 (1): A-36, S11, 2007. Halyard MY, Pisansky TM, Solin LJ, et al.: Adjuvant radiotherapy (RT) and trastuzumab in stage I-IIA breast cancer: toxicity data from North Central Cancer Treatment Group phase III trial N9831. [Abstract] J Clin Oncol 24 (Suppl 18): A-523, 2006. Perez EA, Suman VJ, Davidson NE, et al.: HER2 testing by local, central, and reference laboratories in specimens from the North Central Cancer Treatment Group N9831 intergroup adjuvant trial. J Clin Oncol 24 (19): 3032-8, 2006.[PUBMED Abstract] Miller DV, Jenkins RB, Lingle WL, et al.: Focal HER2/neu amplified clones partially account for discordance between immunohistochemistry and fluorescence in-situ hybridization results: data from NCCTG N9831 intergroup adjuvant trial. [Abstract] J Clin Oncol 22 (Suppl 14): A-568, 19s, 2004. Perez EA, Suman VJ, Davidson NE, et al.: HER2 testing by local, central, and reference laboratories in the NCCTG N9831 intergroup adjuvant trial. [Abstract] J Clin Oncol 22 (Suppl 14): A-567, 19s, 2004. Perez EA, Suman VJ, Davidson NE, et al.: Effect of doxorubicin plus cyclophosphamide on left ventricular ejection fraction in patients with breast cancer in the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial. J Clin Oncol 22 (18): 3700-4, 2004.[PUBMED Abstract] Perez EA, Suman VJ, Davidson NE, et al.: Effect of doxorubicin plus cyclophosphamide (AC) on left ventricular ejection fraction (LVEF) in the NCCTG N9831 intergroup adjuvant trial. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-75, 19, 2003. Roche PC, Suman VJ, Jenkins RB, et al.: Concordance between local and central laboratory HER2 testing in the breast intergroup trial N9831. J Natl Cancer Inst 94 (11): 855-7, 2002.[PUBMED Abstract] Related PublicationsJahanzeb M: Adjuvant trastuzumab therapy for HER2-positive breast cancer. Clin Breast Cancer 8 (4): 324-33, 2008.[PUBMED Abstract] Partridge AH, Wolff AC, Marcom PK, et al.: The impact of sharing results of a randomized breast cancer clinical trial with study participants. Breast Cancer Res Treat : , 2008.[PUBMED Abstract] Reinholz MM, Dueck AC, Lingle WL, et al.: The concordance between NCCTG's and NSABP's C-myc FISH assays. [Abstract] J Clin Oncol 26 (Suppl 15): A-22110, 2008. Garrison LP Jr, Lubeck D, Lalla D, et al.: Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2-positive breast cancer. Cancer 110 (3): 489-98, 2007.[PUBMED Abstract] Kurian AW, Thompson RN, Gaw AF, et al.: A cost-effectiveness analysis of adjuvant trastuzumab regimens in early HER2/neu-positive breast cancer. J Clin Oncol 25 (6): 634-41, 2007.[PUBMED Abstract] Liberato NL, Marchetti M, Barosi G: Cost effectiveness of adjuvant trastuzumab in human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 25 (6): 625-33, 2007.[PUBMED Abstract] Perez E, Romond E, Suman V, et al.: Updated results of the combined analysis of NCCTG N9831 and NSABP B-31 adjuvant chemotherapy with/without trastuzumab in patiens with HER2-positive breast cancer. [Abstract] J Clin Oncol 25 (Suppl 18): 512, 6s, 2007. Telli ML, Hunt SA, Carlson RW, et al.: Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility. J Clin Oncol 25 (23): 3525-33, 2007.[PUBMED Abstract] Baselga J, Perez EA, Pienkowski T, et al.: Adjuvant trastuzumab: a milestone in the treatment of HER-2-positive early breast cancer. Oncologist 11 (Suppl 1): 4-12, 2006.[PUBMED Abstract] Garrison LP, Perez EA, Dueck A, et al.: Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2+ breast cancer. [Abstract] J Clin Oncol 24 (Suppl 18): A-6023, 306s, 2006. Gupta AK, Mekan SF, Eckman MH: Trastuzumab for all? A decision analysis examining tradeoffs between efficacy and cardiac toxicity of adjuvant therapy in HER2 positive breast cancer. [Abstract] J Clin Oncol 24 (Suppl 18): A-6022, 306s, 2006. Romond EH, Perez EA, Bryant J, et al.: Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353 (16): 1673-84, 2005.[PUBMED Abstract] Perez EA, Rodeheffer R: Clinical cardiac tolerability of trastuzumab. J Clin Oncol 22 (2): 322-9, 2004.[PUBMED Abstract] Trial Lead Organizations North Central Cancer Treatment Group
Eastern Cooperative Oncology Group
Cancer and Leukemia Group B
Southwest Oncology Group
NCIC-Clinical Trials Group
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. |
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