A Study of Sunitinib in Combination With Bevacizumab and Paclitaxel in Previously Untreated Patients With Metastatic Breast Cancer (SABRE-B)

Study Overview
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Brief Summary
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This is a multicenter, Phase II, randomized, controlled, open label trial designed to provide a preliminary assessment of the safety and efficacy of sunitinib when combined with bevacizumab and paclitaxel in patients who have not previously received chemotherapy for locally recurrent or metastatic breast cancer.

Official Title
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A Multicenter, Phase II, Randomized, Controlled Trial Evaluating the Efficacy and Safety of Sunitinib in Combination With Bevacizumab and Paclitaxel in Previously Untreated Patients With Metastatic Breast Cancer

Conditions
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Metastatic Breast Cancer

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent Form Histologically or cytologically confirmed adenocarcinoma of the breast with measurable or non-measurable locally recurrent or metastatic disease Age ≥ 18 years Adequate left ventricular function at study entry, defined as an Left Ventricular Ejection Fraction (LVEF) > 50% by either Multi Gated Acquisition(MUGA) scan or Electrocardiogram (ECHO) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Ability and willingness to comply with study and follow-up procedures Exclusion Criteria: Unknown HER2 status or known HER2-positive status Prior chemotherapy for locally recurrent or metastatic disease Prior hormonal therapy within 2 weeks prior to Day 1 Prior adjuvant or neoadjuvant taxane chemotherapy within 12 months prior to Day 1 Prior adjuvant or neoadjuvant non-taxane chemotherapy within 6 months prior to Day 1 For patients who have received recent radiotherapy, ongoing Grade ≥ 3 acute toxicity Patients with brain metastasis on full dose anticoagulation therapy Life expectancy of < 12 weeks Current, recent (within 4 weeks of Day 1), or planned participation in an experimental drug study Inadequate organ function within 28 days prior to Day 1 Untreated abnormal thyroid function tests Uncontrolled serious medical or psychiatric illness Active infection requiring IV antibiotics at enrollment or randomization History of other malignancies within 5 years prior to Day 1 except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix Inadequately controlled hypertension Prior history of hypertensive crisis or hypertensive encephalopathy New York Heart Association (NYHA) Class II or greater CHF History of myocardial infarction or unstable angina within 12 months prior to Day 1 History of stroke or transient ischemic attack within 12 months prior to Day 1 Known central nervous system (CNS) disease except for treated brain metastasis Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within 6 months prior to Day 1 History of hemoptysis within 1 month prior to Day 1 Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1 History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1 Serious, non-healing wound, active ulcer, or untreated bone fracture Proteinuria at screening, as demonstrated by a urine protein/creatinine ratio of ≥ 1.0 at screening Known hypersensitivity to any component of bevacizumab or sunitinib Pregnancy (positive pregnancy test) or lactation

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: 1<br> | Drug: bevacizumab<br>* Intravenous repeating dose<br>Drug: sunitinib<br>* Oral repeating dose<br>Drug: paclitaxel<br>* Intravenous repeating dose<br>|
| Placebo Comparator: 2<br> | Drug: bevacizumab<br>* Intravenous repeating dose<br>Drug: paclitaxel<br>* Intravenous repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Response | The best overall response is the best response, per the Response Evaluation Criteria In Solid Tumors (RECIST) criteria, recorded from randomization until disease progression/recurrence (includes both confirmed and unconfirmed responses). Although the original primary outcome was progression-free survival, there was insufficient data available to report on that outcome. | From randomization until disease progression/recurrence (by patient) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serious Adverse Events (SAEs) | All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0. An SAE is defined as an adverse event that results in death, is life threatening, requires hospitalization, results in significant disability, results in birth defect, or is considered a significant medical event by the investigator | 30 days following the last administration of study treatment | 
| Grade ≥ 3 Adverse Events (AEs) | All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0. Grading: 1=Mild AE; 2=Moderate AE; 3=Severe AE; 4=Life-threatening or disabling AE; 5=Death related to AE | 30 days following the last administration of study treatment | 
| Adverse Events Leading to Death | All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0 | 30 days following the last administration of study treatment | 
| Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction | All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0 | 30 days following the last administration of study treatment | 
| Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption | All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0 | 30 days following the last administration of study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Avastin, MBC, Breast Cancer, Sutent