Phase I Study With Sorafenib in Addition to Vinflunine in Metastatic Transitional Cell Carcinoma of the Urothelial Tract

Exclusion Criteria

• •non-transitional cell carcinoma of the urothelial tract (e.g. pure adenocarcinoma or squamous cell carcinoma);
• •prior treatment with vinflunine;
• •diagnosed brain metastases or leptomeningeal involvement. Brain CT-scans or MRI are not required unless there is clinical suspicion of central nervous system involvement.
• •peripheral neuropathy G3 (NCI CTCAE v4.0);
• •history of serious or concurrent illness or uncontrolled medical disorder; any medical condition that might be aggravated by treatment or which could not be controlled: active infection requiring antibiotics within 2 weeks before the study inclusion, unstable diabetes mellitus, uncontrolled hypercalcaemia \>2.9 mmol/L (or \>G2 NCI CTCAE v4.0), concurrent congestive heart failure NYHA (class III-IV) or any type of angina pectoris and/or a diagnosis of myocardial infarction during the previous 6 months and/or poorly controlled hypertension will be excluded, QTc \>450 ms at baseline, additional risk factors for Torsade de Pointes (heart failure and hypokalemia (≥G1, i.e. P-K \<LLN-2.5 mM) or family history of long QT-syndrome), cardiac arrhythmias requiring anti-arrhythmics (excluding beta-blockers or digoxin for chronic atrial fibrillation);
• •patients having received more than one previous systemic chemotherapy for advanced or metastatic disease;
• •patients who have received any other investigational or anti-cancer therapy 14 days before the inclusion;
• •other malignancies, except adequately treated basal carcinoma of the skin or in-situ cervix carcinoma or incidental prostate cancer (T1a, Gleason score ≤6, PSA \<0.5 ng/ml), or any other tumour with a disease free survival of ≥5 years;
• •pregnant or lactating women;
• •men or women of childbearing potential not employing adequate contraception;
• •any psychological, familial, sociological, or geographical condition which does not permit protocol compliance and medical follow-up.
• •poorly controlled hypertension. At baseline, blood pressure \>150/90 is defined as poorly controlled.
• •renal dysfunction: creatinine clearance \<40 ml/min measured by either iohexol clearance or Cr-EDTA technique.
• •ECOG / WHO Performance Status ≥2
• •presence of hand-foot skin reaction or rash \>G1 at enrolment;
• •known or suspected allergy to the investigational agent or any agents given in association with this trial;
• •current medical treatment with any compound that prolongs QTc