CIRG TORI 010

Study: CIRG/TORI 010 (20050225) 

Title	Multicenter phase II randomized trial, Placebo Controlled AMG706 in Combination with Paclitaxel, or Open-Label Bevacizumab in Combination with Paclitaxel, as First Line Therapy in Women with HER2 Negative Locally Recurrent or Metastatic Breast Cancer
Study Chairs	Wolfgang Eiermann, MD, John Forbes, MD, John Mackey, MD; Miguel Martin, MD; Tadeusz Pienkowski, MD; Dennis Slamon, MD
Publication               Sponsor	Motesanib, or open-label bevacizumab, in combination with paclitaxel, as first-line treatment for HER2-negative locally recurrent or metastatic breast cancer: a phase 2, randomised, double-blind, placebo-controlled study Miguel Martin et al. on behalf of the TRIO 010 investigators [The Lancet Oncology, Early Online Publication, 22 March 2011] 2nd analysis SABCS 2009, by Dr John Mackey from the Cross cancer Institute [abs. 47] CIRG/TORI 010: First Analysis of a Randomized Phase II Trial of Motesanib Plus Weekly Paclitaxel (P) as First Line Therapy in HER2-Negative Metastatic Breast Cancer (MBC). Click here 1st analysis ECCO-ESMO 2009, by Dr Miguel Martin [abs.5001] Amgen, Inc.
Rationale	This study will be the first trial to: Scientifically: Confirm the value of antiangiogenic therapy in breast cancer suggested by E2100 Identify the activity of AMG 706 in breast cancer Practically for patients: This study may show Oral antiangiogenic therapy is safe and effective in advanced breast cancer That small molecule inhibitors may be at least as effective as antibodies.
Design		Paclitaxel 90 mg/mē IV over 1 hour for 3 wks  Blinded AMG 706 Placebo 5 tablets PO QD   Paclitaxel 90 mg/mē IV over 1 hour for 3 wks  Blinded AMG 706 125mg PO QD  Paclitaxel 90 mg/mē IV over 1 hour for 3 wks  Open-Label Bevacizumab 10mg/kg following paclitaxel treatment on wk 1 and wk 3 of each cycle (4 wks)
Major eligibility criteria	- Histologically proven recurrent or metastatic breast cancer - Measurable disease (RECIST) - Complete radiology and tumor measurements within 4 wks - Her2neu negative tumor - Female > 18yrs - ECOG PS: 0 or 1 - Adequate organ and hematological functions - Informed consent
Endpoints	Primary: Response Rate Secondary: Progression Free Survival, Duration of response, Clinical benefit rate, Overall survival, Incidence of adverse events and laboratory abnormalities. Exploratory:Quality of life evaluation, Cardiac Substudies,  Pharmacokinetics studies, biomarker substudies, on effects of genetic variation in drug metabolism genes, cancer genes, and target genes on responders in arm B.
Number of Patients	A total of 273 patients randomized in a 1:1:1 ratio 91 subjects per treatment arm : 80% power to detect a difference of 20% in RR between Arm A and B (2-sided chi-square test with significance level of 0.05, assuming RR=20% in arm A and RR=40% in arm B) 91 subjects are required to estimate the response rate in arm C. Stratification factors: Adjuvant or neoadjuvant chemotherapy (taxane containing regimens vs. other regimens vs. none) Number of metastatic sites (< 3 vs. > 3) Hormone receptor status (positive vs. negative)
Participating countries	AUSTRALIA/NZ, CANADA, FRANCE, GERMANY, HUNGARY, IRELAND, POLAND, SPAIN and USA

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