BCIRG 007

Study: BCIRG 007 (WO16437)

Title	A multicenter phase III randomized trial comparing docetaxel (Taxotere) and trastuzumab (Herceptin) with docetaxel (Taxotere), platinum salt (cisplatin or carboplatin) and trastuzumab (Herceptin) as first line chemotherapy for patients with advanced breast cancer containing the HER2neu alteration
Study Chairs	John Crown, MD, Vicente Valero, MD, Dennis Slamon, MD PhD
Sponsor	F. Hoffman - La Roche Ltd.
Status     Results and Communication                                           Rationale	Enrollment completed on March 2004.   Main efficacy (TTP) and safety results presented at ASCO 2006, and additional information at ESMO 2006 (poster). 1st Overall Survival analysis presented at ASCO 2007, and sub-study results on ECD serum levels and at ECCO-14 (Proffered Papers Breast cancer - advanced disease session presented by Dr Pienkowksi on September 25 2007) . Multicenter Phase III Randomized Trial Comparing Docetaxel and Trastuzumab With Docetaxel, Carboplatin, and Trastuzumab As First-Line Chemotherapy for Patients With HER2-Gene-Amplified Metastatic Breast Cancer (BCIRG 007 Study): Two Highly Active Therapeutic Regimens Vicente Valero, John Forbes, Mark D. Pegram, Tadeusz Pienkowski, Wolfgang Eiermann, Gunter von Minckwitz, Henri Roche, Miguel Martin, John Crown, John R. Mackey, Pierre Fumoleau, Janusz Rolski, Zrinka Mrsic-Krmpotic, Agnieszka Jagiello-Gruszfeld, Alessandro Riva, Marc Buyse, Henry Taupin, Guido Sauter, Michael F. Press, and Dennis J. Slamon (J Clin Oncol 29:149-156, 2011) Preclinical studies from the laboratory of Dr. Dennis Slamon indicate that Taxotere and platinum salts are the most highly synergistic chemotherapies when combined with Herceptin. BCIRG 006 studies this finding in the adjuvant setting while this study does the same in the metastatic setting. The design tests specifically the impact of addition of the platinum salt. 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		TH: docetaxel (100mg/m2) x 8 + Herceptin weekly during chemotherapy then every 21 days until PD  TCH: (T, 75mg/m2 + C*) x 8 + Herceptin weekly during chemotherapy then every 21 days until PD
	*Carboplatin AUC 6
Posters & Slides		BCIRG 007 design slide.ppt download design slide
Major eligibility criteria	Histologically proven breast cancer Metastatic breast cancer. Patients must have either measurable or nonmeasurable lesions according to the RECIST criteria. Tumor must be POSITIVE for HER2neu overexpression by FISH Age 18 - 75 years, KPS > 60% Prior hormonal and adjuvant and/or neadjuvant chemotherapy allowed; if taxane or Herceptin: at least 6 months prior to study registration, if taxane + Herceptin: at least 12 months prior to study registration, if anthracycline: cumulative dose must be as follows: doxorubicin < 360 mg/m2 or epirubicin < 720 mg/m2 or mitoxantrone < 72 mg/mē and treatment stopped at least 4 weeks prior to study registration No prior chemotherapy or Herceptin for advanced disease Normal bone marrow, liver, renal and cardiac function No brain or leptomeningial Informed consent
Endpoints	Primary: Time to disease progression Secondary: - To compare response rate, duration of response, overall survival -To evaluate and compare clinical benefit, defined as CR, PR, or stable disease > 24 weeks. -To compare toxicity between the 2 arms. -To evaluate pathologic and molecular markers for predicting efficacy. -To compare peripheral levels of shed HER2neu extracellular domain (ECD) with FISH determination in predicting outcome to treatment with Herceptin
Number of Patients	250 patients ( 125 per treatment arm ) The following assumptions are made: - the median TTP of HER2neu FISH positive metastatic patients receiving TH will be around 7 months - there will be a 50% improvement in median TTP for patients receiving TCH - the error rate for a false positive outcome (a) is set to 5%, using two- sided significance tests - 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	Australia, Canada, France, Germany, Hungary, Ireland, Spain, Poland, United Kingdom, and USA

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