A Study of Sunitinib in Combination With Bevacizumab and Paclitaxel in Previously Untreated Patients With Metastatic Breast Cancer (SABRE-B)
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: bevacizumab; sunitinib; paclitaxel
Intervention description: Intravenous repeating dose; Oral repeating dose; Intravenous repeating dose
Intervention MeSH terms: Paclitaxel; Bevacizumab; Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Avastin; MBC; Breast Cancer; Sutent

Summary:

      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.
    

Eligibility criteria:

        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