A Study Of SU011248 Plus Paclitaxel Versus Bevacizumab Plus Paclitaxel In Patients With Advanced Breast Cancer

• Progression-Free Survival (PFS) [ Time Frame: From date of randomization through Day 1 and every 8 weeks thereafter up to 18 months or death ] [ Designated as safety issue: No ]
  Time from date of randomization to the date of the first documentation of objective tumor progression or death due to any cause, whichever occurred first. PFS = (first event date minus randomization date +1) divided by 30.4
  
  

• Number of Participants With Objective Response [ Time Frame: From date of randomization through Day 1 and every 8 weeks thereafter up to 18 months ] [ Designated as safety issue: No ]
  Objective response = participants with confirmed complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST). A CR was defined as the disappearance of all target lesions. A PR was defined as a > = 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
  
  
• Duration of Response (DR) [ Time Frame: From date of randomization through Day 1 and every 8 weeks thereafter up to 18 months or death due to any cause ] [ Designated as safety issue: No ]
  DR=time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to first documentation of objective disease progression or death due to any cause, whichever was first. DR was calculated as [the date response ended (ie, date of progressive disease or death) minus first CR or PR date that was subsequently confirmed +1)] divided by 30.4.
  
  
• Overall Survival (OS) [ Time Frame: From date of randomization up to 5 years. Survival follow-up changed to 28-days after treatment discontinuation when study was discontinued. ] [ Designated as safety issue: No ]
  OS was defined as the time from date of randomization to death due to any cause. OS (in months) was calculated as (date of death minus randomization date +1) divided by 30.4.
  
  
• Percentage of Participants Surviving at 1 and 2 Years [ Time Frame: Year 1, Year 2 ] [ Designated as safety issue: No ]
  Percentage of those surviving at the end of one year or end of 2 years from the first dose of study treatment.
  
  
• European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) [ Time Frame: Day 1 of Cycles 1 through 7 and then odd-numbered cycles thereafter until 18 months ] [ Designated as safety issue: No ]
  EORTC QLQ-C30: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
  
  
• EORTC QLQ Breast Cancer Module (BR23) [ Time Frame: Day 1 of Cycles 1 through 7 and then odd-numbered cycles thereafter until 18 months ] [ Designated as safety issue: No ]
  BR23: measured disease related symptoms of dry mouth, eye pain, hair loss, hot flushes, attractiveness, future health, sexual activity, arm/shoulder pain, breast pain, swollen breast, and skin problems on the breast. Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.
  
  
• Euro Quality of Life-5 Dimension (EQ-5D) [ Time Frame: Day 1 of Cycles 1 through 7 and then odd-numbered cycles thereafter until 18 months ] [ Designated as safety issue: No ]
  EQ-5D: health status in 5 dimensions (mobility, self-care, pain/discomfort, anxiety/depression, usual activities). Three-level scale (1=no problem, 2=some problem, and 3=extreme problem). A single score between 1 and 3 is generated for each domain. For each subject, the outcome rating on the 5 domains could be mapped to a single index through an algorithm. The index ranges between 0 and 1, with the higher score indicating a better health state perceived by the subject.
  
  
• EQ - Visual Analog Scale (EQ-VAS) [ Time Frame: Day 1 of Cycles 1 through 7 and then odd-numbered cycles thereafter until 18 months ] [ Designated as safety issue: No ]
  EQ-VAS score on the self-rated "thermometer," indicating the patient's own assessment of their health status from 0 (worst) to 100 (best) imaginable health state.
  
  
• Biomarkers [ Time Frame: Day 1 of Cycles 1 through 3 and 5, Day 8 of Cycle 1, and Day 15 of Cycle 1 ] [ Designated as safety issue: No ]
  Concentrations of plasma proteins (eg, soluble Vascular Endothelial Growth Factor Receptor 2 [VEGFR2] and VEGFR3, VEGF-A, placental growth factor [PlGF], soluble KIT, and possibly soluble PDGFRβ and PDGF) that may be associated with angiogenesis and tumor proliferation.
  
  

On May 27, 2009, the independent Data Monitoring Committee (DMC) reviewed the progress of Study A6181094. The DMC determined Study A6181094 had met pre-specified futility criteria and was unlikely to meet its primary endpoint to demonstrate a statistically significant improvement in progression-free survival (PFS) in patients treated with sunitinib plus paclitaxel versus bevacizumab plus paclitaxel. Pfizer notified clinical trial investigators involved in the study and regulatory agencies of these findings. Enrollment in this study has been stopped.