Pazopanib in Combination With Capecitabine in Patients With Metastatic Breast Cancer

Inclusion Criteria

• Written informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures.
• Complete baseline documentation must be submitted via the web-based data collection system MedCODES to the GBG Forschungs GmbH.
• Diagnosis of advanced or metastatic HER2-negative breast cancer. HER2-negative is defined as HercepTest IHC 0-2+ or FISH negative (ratio 18 years.
• Karnofsky Performance Status index => 60%.
• Laboratory requirements: Absolute neutrophil count (ANC) => 1.5 x 109/L, Platelets => 100 x 109/L, Hemoglobin => 9 g/dL (=> 5.6 mmol/L), Prothrombin time (PT) or international normalised ratio (INR) = 50 mL/min), Urine Protein to Creatinine Ratio (UPC) 1, then 24-hour urine protein must be 1 and/or that is progressing in severity, except alopecia.
• Surgery or tumor embolisation within 28 days prior to the first dose of pazopanib. At least 4 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiated field or there must be pathological proof of progressive disease.
• Concurrent immuno-biological or hormonal therapy for cancer.
• History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug.
• Life expectancy less than 3 months.
• History of thyroid autoimmune disease or thyroid disorders with thyroid values out of standard range
• Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: Active peptic ulcer disease, Known intraluminal metastatic lesion/s with risk of bleeding, Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation, History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
• Severe liver dysfunction
• Grade 3 or 4 diarrhea.
• Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: Malabsorption syndrome, Major resection of the stomach or small bowel.
• Presence of uncontrolled infection.
• History of any one or more of the following cardiovascular conditions within the past 6 months: Cardiac angioplasty or stenting, Myocardial infarction, Unstable angina, Coronary artery bypass graft surgery, Symptomatic peripheral vascular disease, Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA), Poorly controlled hypertension (defined as systolic blood pressure [SBP] of ≥ 160 mmHg or diastolic blood pressure [DBP] of ≥ 90 mmHg).

Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry.

BP must be re-assessed on two occasions that are separated by a minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP/DBP values from each BP assessment must be < 160/95 mmHg in order for a subject to be eligible for the study (see Section 9.6.1 for details on BP control and re-assessment prior to study enrollment).

• History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible.
• Evidence of active bleeding or bleeding diathesis including, but not limited to: Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major), Known endobronchial lesions and/or lesions i