Inclusion Criteria:

1. Patients ≥ 18 years of age with histologically confirmed, metastatic breast cancer
resistant to anthracyclines and taxanes

2. Anthracycline resistance is defined as tumor progression during treatment or within 3
months of last dose in the metastatic setting, or recurrence within 6 months in the
neoadjuvant or adjuvant setting

3. Taxane resistance is defined as recurrence within 4 months of the last dose in the
metastatic setting or within 12 months in the adjuvant setting

4. Having progressed on anti-HER2 or hormonal therapy if they have HER2 positive or
hormone-receptor positive breast cancer

5. Eastern Cooperative Oncology Group (ECOG) performance status score < 2 and a life
expectancy >3 months.

6. Participants must have at least one target lesion as defined by RECIST 1.1 that
allows for evaluation of tumor response

7. Absolute neutrophil count > 1500 mm3, platelet count ≥ 100×109 L, hemoglobin ≥ 8.5
g/dL

8. Serum creatinine ≤1.5 times the upper limit of the normal range, total bilirubin ≤ 2
mg/dL, AST/ALT ≤ 5 times the upper limit of normal range

9. No remaining grade 2 or higher toxicity from prior cancer therapies unless judged to
be clinically insignificant by the Principal Investigator

10. At least three (3) weeks from prior chemotherapy

11. At least four (4) weeks from prior major surgery

12. Willingness to participate in collection of pharmacokinetic samples during cycle 1 of
the study

13. Willingness to provide permission to access archived tumor samples and blood samples

14. Women of child-bearing potential (i.e., women who are pre-menopausal or not
surgically sterile) must be willing to use an acceptable contraceptive method
(abstinence, oral contraceptive or double barrier method) for the duration of the
study and for 30 days following the last dose of study drug, and must have a negative
urine or serum pregnancy test within 2 weeks prior to beginning treatment on this
trial.

Exclusion Criteria:

1. Inadequate renal function with a calculated creatinine clearance less than 51 mL/min.

2. History of ventricular fibrillation, sinus node or AV nodal disease, Wolff Parkinson
White Syndrome, hemodynamically significant or life threatening cardiac arrhythmia.

3. Uncontrolled cardiac disease, congestive heart failure, angina or hypertension.

4. Myocardial infarction or unstable angina within 2 months of treatment.

5. Known human immunodeficiency virus (HIV) infection or chronic active Hepatitis B or C
(patients are NOT required to be tested for the presence of such viruses prior to
therapy on this protocol).

6. Active clinically serious infection > CTCAE (version 4.03) Grade 2.

7. Thrombotic or embolic events such as a cerebrovascular accident including transient
ischemic attacks within the past 6 months.

8. Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of
study drug.

9. Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of
study drug.

10. Serious non-healing wound, ulcer, or bone fracture.

11. Major surgery, open biopsy or significant traumatic injury within 4 weeks of first
study drug.

12. Inability to complete informed consent process and adhere to the protocol treatment
plan and follow-up requirements.

13. Concurrent severe illness such as active infection, or psychiatric illness/social
situations that would limit safety and compliance with study requirements.

14. Currently on anti-coagulation therapy with Coumadin, and cannot be switched other
forms of anti-coagulation.

15. Patients have symptomatic untreated brain metastasis or leptomeningeal metastases or
treated but still symptomatic requiring the use of steroid.

16. Patients receiving any other investigational agents. Pregnant or Lactating females