Pazopanib and Vinflunine in Urothelial Cancer of the Bladder

Inclusion Criteria: * Written informed consent * Age ≥ 18 years * Histologically confirmed Transitional Cell Carcinoma of the Urothelium (TCCU) with lymphatic (N-stage 2-3) and/or distant metastases (M-stage 1) not amenable to definitive regional/local therapy * Progression of tumor disease after platinum containing systemic chemotherapy for advanced or metastatic disease * Eastern Cooperative Oncology Group (ECOG) performance status of 1 * estimated minimal life expectancy of 3 months at screening * At least one measurable tumor lesion according to RECIST 1.1 criteria * Adequate organ system function at screening * Adequate contraception Exclusion Criteria: * More than 1 prior chemotherapy, biologic therapy or hormonal therapy within 14 days prior to the first dose of study medication * Prior malignancy within 5 years prior to inclusion (exception: successfully treated basal cell carcinoma or in situ carcinoma) * History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis * Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding within 28 days prior to beginning study treatment, e.g * 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 intraabdominal abscess * Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product, e.g. * Malabsorption syndrome * Major resection of the stomach or small bowel * Active infection requiring antibiotics within 14 days before registration * Corrected QT interval (QTc) \> 480 msecs using Bazett's formula at screening * Screening-electrocardiogram (ECG) with any significant modifi¬cations suggesting a high risk of occurrence of an acute clinical event (such as signs of angina pectoris, high risk arrhythmia etc.) * History of one or more of the following cardiac / cardiovascular conditions within the past 6 months before registration: * Cardiac angioplasty or stenting * Myocardial infarction * Unstable angina * Coronary artery bypass graft surgery * Symptomatic peripheral vascular disease * NYHA Class II, III or IV congestive heart failure * Uncontrolled cardiac arrhythmia * Poorly controlled hypertension, defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90 mmHg * History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months before registration * Peripheral neuropathy grade ≥ 2 (NCI CTC v3.0) * Unstable diabetes mellitus * Uncontrolled hypercalcaemia \> 2.9 mmol/L * Prior major surgery or trauma within 28 days prior to registration and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major) * Evidence of active bleeding e.g. GI bleeding or bleeding diathesis at screening. * Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels * Hemoptysis with bleeding of \> 2.5 mL within 8 weeks before registration * Any serious and/or unstable pre-existing medical, psychiatric/psychological, familial, sociological, geographical or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures * prior to the first dose of study drug and for the duration of the study * Radiation, surgery or tumor embolization or any investigational treatment within 14 days prior to the first dose of study medication * Any ongoing toxicity from prior anti-cancer therapy that is \> Grade 1 and/or progressing in severity, except nausea, vomiting, alopecia * ASA 4 * Pre-treatment with Pazopanib or Vinflunine * Pregnancy or lactation