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

Phase 2

Terminated

Conditions: Metastatic Breast Cancer

Interventions: Drug: bevacizumab
Drug: sunitinib
Drug: paclitaxel

Registration Number: NCT00434356

Lead Sponsor: Genentech, Inc.

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 46

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	bevacizumab	-
1	paclitaxel	-
2	bevacizumab	-
2	paclitaxel	-
1	sunitinib	-

Primary Outcome Measures

Name	Time	Method
Best Response	From randomization until disease progression/recurrence (by patient)	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.

Secondary Outcome Measures

Name	Time	Method
Serious Adverse Events (SAEs)	30 days following the last administration of study treatment	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
Grade ≥ 3 Adverse Events (AEs)	30 days following the last administration of study treatment	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
Adverse Events Leading to Death	30 days following the last administration of study treatment	All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0
Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction	30 days following the last administration of study treatment	All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0
Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption	30 days following the last administration of study treatment	All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0