Bevacizumab and Abraxane as Second-line Therapy in Triple Negative Metastatic Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the addition of bevacizumab to Abraxane as second-line therapy in Her-2 negative, hormone receptor negative metastatic breast cancer.

Official Title
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A Phase II Trial of Bevacizumab and ABI-007 (Abraxane) as Second-line Therapy in Her-2 Negative, Hormone Receptor Negative Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Bevacizumab, Abraxane


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female, aged 18 years or older and able to give informed consent. Histologically- or cytologically-proven adenocarcinoma of the breast at time of first diagnosis ECOG performance status 0 or 1 Life expectancy > 12 weeks Stage IV disease and have at least one lesion measurable by standard RECIST criteria Disease progression after at least one prior chemotherapy regimen for metastatic disease or within 12 months of adjuvant chemotherapy initiation. All chemotherapy must be stopped > 2 weeks before enrollment. Primary or metastatic tumor must be negative for estrogen and progesterone receptor expression. Testing must be done in a CLIA-approved laboratory. Primary or metastatic tumor must have 0 or 1+ staining for HER2/neu identified immunohistochemically (IHC), by an approved method using one of the standard monoclonal or polyclonal antibodies (HercepTest, cb-11, PAb1, or TAB250), or if FISH status is known, it must be negative. Testing must be done in a CLIA-approved laboratory. Left ventricular ejection fraction must be >= institutional lower limit of normal as determined by MUGA or echocardiogram Patient must be able to comply with treatment and follow-up procedures: Adequate bone marrow, liver and renal function; Absolute neutrophil count >= 1500/mm3; Hemoglobin >= 10 g/dl; Platelet count >= 100,000/mm3; Creatinine <= 2.0; PTT and either INR or PT < 1.5x normal; Total bilirubin <= 1.5 X upper limit of normal; AST, ALT, and alkaline phosphatase <= 2 X upper limit of normal (or <= 5X upper limit of normal if known liver metastases) If female is of childbearing potential, pregnancy test must be negative and patient must be willing to use effective contraception while on treatment and for at least 3 months after the last dose of study medication Exclusion Criteria: Prior treatment with VEGF targeted therapy Prior taxane therapy for metastatic disease or for adjuvant therapy within the previous 12 months History of prior cancer, excluding carcinoma in situ of the cervix and non-melanoma skin cancers Known CNS disease Inadequately controlled hypertension (defined as systolic blood pressure>150 and/or diastolic blood pressure>100 mmHg on antihypertensive medications) Any prior history of hypertensive crisis or hypertensive encephalopathy New York Heart Association (NYHA) Grade II or greater congestive heart failure History of myocardial infarction or unstable angina within 6 months prior to study enrollment History of stroke or transient ischemic attack within 6 months prior to study enrollment Significant vascular disease (e.g., aortic aneurysm, aortic dissection) Symptomatic peripheral vascular disease Evidence of bleeding diathesis or coagulopathy Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment 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 study enrollment History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment Serious, non-healing wound, ulcer or bone fracture Proteinuria at screening as demonstrated by either: Urine protein:creatinine (UPC) ratio >1.0 at screening OR Urine dipstick for proteinuria >2+ (patients discovered to have >2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate <1g of protein in 24 hours to be eligible) Patients with active infection Women who are pregnant or lactating Radiation therapy within 3 weeks of study entry Patients with hypersensitivity to ABI-007, Chinese hamster ovary cell products, or other recombinant human antibodies Baseline neuropathy > grade 2 Participation in an investigational study of an antineoplastic agent within 4 weeks of first infusion of this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bevacizumab and ABI-007 (Abraxane)<br>Bevacizumab and ABI-007 (Abraxane) | Drug: Bevacizumab, Abraxane<br>* Bevacizumab, 10 mg/m2 IV days 1 and 15; ABI-007, 100 mg/m2 IV days 1, 8, 15 of each 28 day cycle. Continue treatment until disease progression, patient withdrawal or unacceptable toxicities.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine progression-free survival among women receiving bevacizumab + ABI-007 given as second-line combination therapy for hormone receptive negative, Her-2 negative metastatic breast cancer. |  | Study Completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the overall response rate to bevacizumab + ABI-007 in this study population. |  | Study completion | 
| To determine the toxicity of bevacizumab + ABI-007 in this study population. |  | Study completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Metastatic breast cancer, Second-Line Therapy, Triple Negative, Her-2 negative, Hormone receptor negative, Abraxane, Bevacizumab