Phase II Pazopanib in Combination With Weekly Paclitaxel in Refractory Urothelial Cancer

Inclusion Criteria

• Histologically confirmed transitional cell carcinoma (TCC) of the urothelium (bladder, renal pelvis, ureter, or urethra). Mixed histology is allowed as long as the predominant histology is TCC
• First recurrence after treatment with a maximum of two chemotherapeutic regimens.
• Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up.

Procedures conducted as part of the subject's routine clinical management (eg, blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol.

• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Measurable disease criteria by RECIST criteria
• Adequate organ system function as defined below
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
• Hemoglobin ≥ 9 g/dL
• Platelets ≥ 100 X 10^9/L
• Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.2 x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 x ULN
• aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT)≤ 2.5 x ULN
• Serum creatinine ≤ 1.8 mg/dL
• Urine Protein to Creatinine Ratio (UPC) 480 milliseconds. On antiarrhythmics or medications known to prolong QT interval
• 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 by-pass 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 ≥ 140 mmHg or diastolic blood pressure (DBP) of ≥ 90mm Hg].
• History of cerebrovascular accident, hemoptysis, cerebral hemorrhage, clinically significant GI bleed, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
• Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture
• Evidence of active bleeding or bleeding diathesis.
• Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to procedures.
• Patients on strong CYP3A4 inhibitors
• Uncorrected abnormal electrolytes: K, Mg and Ca
• Prior treatment with taxane chemotherapy
• Treatment with any of the following anti-cancer therapies:
• radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR
• chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib