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

Study Overview
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Brief Summary
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To compare treatment with SU011248 plus paclitaxel versus bevacizumab plus paclitaxel to determine which treatment works better against breast cancer

Detailed Description
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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.

Official Title
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A Phase 3 Study Of SU011248 In Combination With Paclitaxel Versus Bevacizumab With Paclitaxel In The First-Line Advanced Disease Setting In Patients Having Breast Cancer

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Drug: Sunitinib
* Drug: paclitaxel
* Drug: bevacizumab
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of advanced breast cancer. Measurable disease as per RECIST (Response Evaluation Criterion) in Solid Tumors or bone-only disease. ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1. Exclusion Criteria: No prior treatment with cytotoxics in the advanced disease setting. HER2/neu positive disease unless trastuzumab was previously received or is contraindicated. Treatment with a taxane in the adjuvant setting unless disease free interval >12 months after end of treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: Sunitinib<br>* Sunitinib 25 mg daily by oral capsules with titration up to 37.5 mg,<br>* Other names: SU011248, Sutent;Drug: paclitaxel<br>* Paclitaxel 90 mg/m2 IV, 3 weekly doses every 28 days until progression or unacceptable toxicity.<br>|
| Active Comparator: B<br> | Drug: bevacizumab<br>* Bevacizumab 10 mg/kg IV every 2 weeks.<br>* Other names: Avastin;Drug: paclitaxel<br>* Paclitaxel 90 mg/m2 IV, 3 weekly doses every 28 days until progression or unacceptable toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | 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 | From date of randomization through Day 1 and every 8 weeks thereafter up to 18 months or death | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Objective Response | 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. | From date of randomization through Day 1 and every 8 weeks thereafter up to 18 months | 
| Duration of Response (DR) | 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. | From date of randomization through Day 1 and every 8 weeks thereafter up to 18 months or death due to any cause | 
| Overall Survival (OS) | 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. | From date of randomization up to 5 years. Survival follow-up changed to 28-days after treatment discontinuation when study was discontinued. | 
| Percentage of Participants Surviving at 1 and 2 Years | Percentage of those surviving at the end of one year or end of 2 years from the first dose of study treatment. | Year 1, Year 2 | 
| European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) | 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. | Day 1 of Cycles 1 through 7 and then odd-numbered cycles thereafter until 18 months | 
| EORTC QLQ Breast Cancer Module (BR23) | 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. | Day 1 of Cycles 1 through 7 and then odd-numbered cycles thereafter until 18 months | 
| Euro Quality of Life-5 Dimension (EQ-5D) | 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. | Day 1 of Cycles 1 through 7 and then odd-numbered cycles thereafter until 18 months | 
| EQ - Visual Analog Scale (EQ-VAS) | 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. | Day 1 of Cycles 1 through 7 and then odd-numbered cycles thereafter until 18 months | 
| Biomarkers | 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. | Day 1 of Cycles 1 through 3 and 5, Day 8 of Cycle 1, and Day 15 of Cycle 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, advanced, sunitinib, bevacizumab, paclitaxel, Phase 3