BCIRG 006

BCIRG 006 (GMA TAX302) 

Multicenter phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (ACT) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (ACTH) and with docetaxel, carboplatin and trastuzumab (TCH) in the adjuvant treatment of node positive and high risk node negative patients with operable breast cancer containing the HER2neu alteration

Status	CIRG Press Release on FDA approval for the TCH arm used in its BCIRG 006 study dated May 29 2008 "Role of anthracycline -based therapy in the adjuvant treatment of breast cancer: efficacy analyses determined by molecular subtypes of the disease" SABCS 2007, D. Slamon, MD, PhD Slamon D, Mackey J, Robert N, Crown J, Martin M, Eiermann W, Pienkowski T, Bee V, Taupin H, Villalobos, Lindsay MA, Riva A, Hurvitz S, Glaspy J, Pauletti G, Sauter G, Press M, CIRG Edmonton Alberta Canada  [abs. 13] BCIRG 006: Quality of life of patients treated with docetaxel and trastuzumab-based regimens in node positive and high risk node negative HER2 positive early breast cancer" Poster by Dr. Au from the Cross Cancer Institute in Edmonton Alberta (Canada)  [Abs. 3064] Heather-Jane Au, N Robert, W Eiermann, T Pienkowski, J Crown, M Martin, M Pawlicki, A Chan, V Bee and D Slamon. Breast Cancer International Research Group (BCIRG), Edmonton, AB, Canada. 2nd analysis presented at SABCS 2006
Study Chairs	Dennis Slamon, MD, John Crown, MD, Tadeusz Pienkowski, MD
Sponsor	Sanofi-Aventis Oncology
Rationale	This study is based on the hypothesis that the high level of increased survival seen in the metastatic setting with Herceptin combined with chemotherapy will translate into increased disease free and overall survival in the adjuvant treatment of patients with tumors overexpressing the HER2neu proto-oncogene. It explores, in the clinical setting, the use of the two chemotherapies (Taxotere and platinum salts) that have shown the greatest level of synergy with Herceptin when combined; based on the laboratory findings of Dennis Slamon at UCLA. In addition, the TCH arm has the advantage of not containing an anthracyline component as the combination of Herceptin and anthracyclines has been shown to increase the cardiac toxicity of both agents. Another important feature of this trial is the use of the FISH test to determine HER2neu status. The feasibility of the TCH arm has been confirmed in two phase II studies, BCIRG 101 and 102.
Design		AC  T AC (60/600 mg/mē) q21days x 4 cycles docetaxel (100mg/mē) q21days x 4 cycles AC  TH AC (60/600mg/mē)q21days x 4 cycles docetaxel (100mg/mē) q21days x 4 cycles + trastuzumab qwkly during chemotherapy then 21days until 1 yr TCH docetaxel (75mg/mē) + carboplatin (AUC 6), + trastuzumab qwkly during chemotherapy then 21days until 1 yr
	*Carboplatin AUC 6
Posters & Slides		BCIRG 006 design slide.pdf  download design slide
Major eligibility criteria	Histologically proven breast cancer Definitive surgical treatment is mastectomy or BCT (must include axillary LN dissection) within 60 days of registration Stage T 1-3, N0 or N1, M0 One, of at least 6 resected nodes, positive for tumor; or zero among a minimum of 6 resected lymph nodes or negative sentinel node biopsy AND at least one of the following risk factors: Tumor size > 2 cm, estrogen receptor and progesterone receptor status is negative, histologic and/or nuclear grade 2-3, or age < 35 years Tumor must be POSITIVE for HER2neu overexpression by FISH Age 18 - 70 years, KPS > 80% Normal bone marrow, liver, renal and cardiac function No prior systemic therapy or RT for breast cancer Informed consent
Endpoints	Primary: Disease Free Survival Secondary: Overall Survival, toxicity and quality of life, cardiac toxicity, and to evaluate pathologic and molecular markers for predicting efficacy.
Number of Patients	A total of 3,200 patients The following assumptions are made: the proportions of patients who have no axillary lymph nodes involved (N0), 1 to 3 axillary lymph nodes involved (N1-3) and 4 or more axillary lymph nodes involved trial (N4+) will be, respectively, 20%, 50% and 30% the DFS at 5 years of patients receiving ACT in these strata are, respectively, equal to about 67%, 57% and 42% the overall DFS of all patients receiving ACT will be equal to about 55% (20% x 67% + 50% x 57% + 30% x 42%) it is of clinical interest to detect a 7% improvement in 5-year DFS (i.e. an increase from 55% to 62%) the overall error rate for a false positive outcome (a) is set to 5%, using two-sided significance tests. Since the three pairwise treatment comparisons will be of interest in the final analysis, the error rate for each comparison is set at a conservative level of 0.017 the error rate for a false negative outcome (b) is set to 20% i.e the power of the trial is set to 80% for the difference of clinical interest
Participating countries	Argentina, Austria, Australia / NZ, Belgium, Bosnia, Brazil, Bulgaria,, Canada, Colombia, Croatia, Czech Republic, Egypt, Estonia, France, Germany, Greece, Hong Kong, Hungary, India, Ireland, Israel, Italy, Lebanon, Mexico, Poland, Portugal, Romania, Russia, Saudi Arabia, Slovakia, Slovenia, South Africa, South Korea, Singapore, Spain , Sweden, Switzerland, Taiwan, United Kingdom, Uruguay, USA, Venezuela

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