ZD6474 (Zactima) and Metronomic Chemotherapy in Advanced Breast Cancer

• Patients must have histologically or cytologically confirmed Stage IV breast cancer
• Patients may have prior treatment with 0-4 prior chemotherapeutic regimens for metastatic disease.
• 18 years of age and older
• Life expectancy of greater than 3 months as assessed by patient's primary oncologist
• ECOG Performance Status of 0-2.
• LVEF > 45%, as assessed by echocardiogram or nuclear medicine gate study within 30 days prior to initiating protocol-based treatment
• Negative Serum pregnancy test
• No receipt of any investigational agents within 30 days prior to commencing study treatment

Exclusion Criteria:

• Abnormal laboratory results as outlined in the protocol
• Therapeutic anti-coagulation. The use of low dose warfarin, intermittent doses of TPA, or heparin flushes to prophylax against central venous catheter associated clots is acceptable.
• Brain metastases or spinal cord compression, unless treated at least 4 weeks before entry and stable without steroid treatment for one week. Leptomeningeal disease is not eligible.
• Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate
• Clinically significant cardiac event such as myocardial infarction; NYHA classification of heart disease greater than or equal to 2; or presence of cardiac disease that increases the risk of ventricular arrhythmia
• History of arrhythmia which is symptomatic or requires treatment or asymptomatic sustained ventricular tachycardia
• Previous history of QTc prolongation as a result from other medication that required discontinuation of that medication
• Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age
• Presence of left bundle branch block
• QTc with Bazett's correction that is unmeasurable or greater than 480msec on screening ECG.
• Any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes or induce CYP3A4 function
• Hypertension not controlled by medical therapy
• Currently active diarrhea that may affect the ability of the patient to absorb the Zactima or tolerate diarrhea
• Previous or current non-breast malignancies within the last 5 years, with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
• Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy
• Patients with large or rapidly accumulating pleural or abdominal effusions
• Women who are currently pregnant or breastfeeding