A Phase II Study Of Abraxane and Nexavar in the First-Line Treatment of Locally Advanced or Metastatic Breast Cancer
1. Patients must have signed an IRB-approved informed consent.
2. Patients must have histologically confirmed locally advanced or metastatic breast
3. Patients must be HER2-negative.
4. Patients must have measurable disease, as defined by the RECIST criteria.
5. Patients may have received prior adjuvant chemotherapy for breast cancer, including
taxane-containing regimens, provided this treatment was completed at least 12 months
prior to enrollment.
6. Patients must be <18 years of age.
7. Patients must have an ECOG Performance Status of 0 or 1.
8. Patients' estimated life expectancy must be at least 12 weeks.
9. Patients must have adequate liver functions defined as: total bilirubin within normal
limits and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 X upper
limit of normal (ULN) (or < 5 X ULN for patients with liver involvement).
10. Patients must have alkaline phosphatase ≤ 2.5 X ULN. Alkaline phosphatase may be >
2.5 x ULN if bone metastasis is present in the absence of liver metastasis, and the
patient's bilirubin ≤ ULN.
11. Patients must have adequate renal function defined as: creatinine ≤ 1.5 mg/dL.
12. Patients must have adequate bone marrow function, including absolute neutrophil count
(ANC) >1500/µL, platelet count >100,000/µL, and hemoglobin >9 g/dL.
13. Patients must have a normal baseline left ventricular ejection fraction (LVEF).
14. Patients must be normotensive. Patients taking anti-hypertensive medication must have
blood pressure controlled and not greater than 140/90.
15. International Normalized Ratio (INR) < 1.5 or a prothrombin time (PT)/partial
thromboplastin time (PTT) within normal limits.
16. Patients must either be not of child bearing potential or have a negative serum
pregnancy test within 7 days prior to registration. Patients are considered not of
child bearing potential if they are surgically sterile (they have undergone a
hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or they are
postmenopausal for at least 12 months.
17. Patients of childbearing potential must agree to use effective contraceptive measures
during study treatment and for a reasonable time thereafter.
18. Patients must be willing and able to comply with scheduled visits, treatment plan and
laboratory testing, and be accessible for follow-up.
1. Patients who have received prior chemotherapy for the treatment of locally advanced
or metastatic breast cancer.
2. Patients who have received prior Abraxane or Nexavar.
3. Patients who have a history of hypersensitivity or a suspected allergy to taxanes,
any of the components in taxanes, Abraxane, or Nexavar.
4. Patients with serious intercurrent medical or psychiatric illness, including serious
5. Patients with untreated or active brain metastases. Patients with neurological
symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
6. Patients with a history of thrombosis.
7. Patients with thrombolic or embolic events such as a cerebrovascular accident
including transient ischemic attacks within the past 6 months.
8. Patients with symptomatic congestive heart failure or a baseline echocardiogram with
LVEF < ULN.
9. Patients with congestive heart failure > class II New York Heart Association (NYHA).
Patients must not have unstable angina (anginal symptoms at rest), or new onset
angina (began within the last 3 months), or myocardial infarction within the past 6
10. Patients with cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
11. Patients with a history of, or active, bowel perforation or inflammatory bowel
12. Patients with active peptic ulcer disease or symptoms to suggest possible ulcer
(discontinuation of chronic NSAID therapy advised, or if not possible, use of
proton-pump inhibitors recommended.)
13. Patients planning to receive any concurrent therapy to treat locally advanced or
metastatic breast cancer during the study treatment period.
14. Any patient who is pregnant or lactating.
15. Patients with proteinuria > +1 by baseline dipstick, or if +2, 24-hour urine total
protein > 250 mg.
16. Patients who have undergone major surgery, open biopsy, or significant traumatic
injury within 28 days, or minor surgery within 14 days. (The placement of a Mediport
or other vascular access device is permitted if performed at least 7 days prior to
17. Patients with > Grade 2 peripheral neuropathy (NCI-CTC v3.0) or any painful
18. Patients who have experienced any type of bone fracture within 12 months or who have
undergone joint replacement surgery within 6 months.
19. Patients with a serious non-healing wound.
20. Patients with known human immunodeficiency virus (HIV) infection or chronic Hepatitis
B or C.
21. Patients requiring anticoagulants (with the exception of low-dose Coumadin, ASA,
Plavix or Heparin for maintenance of vascular access patency).
22. Patients with evidence or history of bleeding diathesis or coagulopathy.
23. Patients experiencing any other hemorrhage/bleeding event > CTCAE Grade 3 within 4
weeks of first dose of study drug.
24. Patients with pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of
first dose of study drug.
25. Patients with any condition that impairs a patient's ability to swallow whole pills
or patients with any malabsorption problems.
26. Patients who use St. John's Wort or rifampin (rifampicin).