Advanced urothelial carcinoma of the bladder MedDRA version: 12.1 Level: LLT Classification code 10046714 Term: Urothelial carcinoma bladder
Conditions
Sponsors
Städtische Kliniken Neuss, Lukaskrankenhaus GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent 2. Age = 18 years 3. 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 4. Progression of tumor disease after platinum containing systemic chemotherapy for advanced or metastatic disease 5. Eastern Cooperative Oncology Group (ECOG) performance status of 1 6. estimated minimal life expectancy of 3 months at screening 7. At least one measurable tumor lesion according to RECIST 1.1 criteria 8. Adequate organ system function at screening 9. Adequate contraception Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. More than 1 prior chemotherapy, biologic therapy or hormonal therapy within 14 days prior to the first dose of study medication 2. Prior malignancy within 5 years prior to inclusion (exception: successfully treated basal cell carcinoma or in situ carcinoma) 3. History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis 4. 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 5. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product, e.g. • Malabsorption syndrome • Major resection of the stomach or small bowel 6. Active infection requiring antibiotics within 14 days before registration 7. Corrected QT interval (QTc) > 480 msecs using Bazett’s formula at screening 8. 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.) 9. 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 10. Poorly controlled hypertension, defined as systolic blood pressure (SBP) of =140 mmHg or diastolic blood pressure (DBP) of = 90 mmHg 11. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months before registration 12. Peripheral neuropathy grade = 2 (NCI CTC v3.0) 13. Unstable diabetes mellitus 14. Uncontrolled hypercalcaemia > 2.9 mmol/L 15. 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) 16. Evidence of active bleeding e.g. GI bleeding or bleeding diathesis at screening. 17. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels 18. Hemoptysis with bleeding of > 2.5 mL within 8 weeks before registration 19. 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 20. Inability or unwillingness to discontinue use of prohibited medications prior to the first dose of study drug and for the duration of the study 21. Radiation, surgery or tumor embolization or any investigational treatment within 14 days prior to the first dose of study medication 22. Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or progressing in severity, except nausea, vomiting, alopecia 23. ASA 4 24. Pre-treatment with Pazopanib or Vinflunine 25. Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: Determination of maximum-tolerated dose (MTD) of pazopanib as add-on to vinflunine standard therapy Phase II: Evaluation of efficacy (in terms of progression-free survival of drug combination at MTD level;Secondary Objective: Phase I: To obtain first data on the efficacy of the com¬bination and to further characterize tolerability. Phase II: Futher assessment of safety, overall survival;Primary end point(s): Phase I: Proportion of patients with dose-limiting toxicity (DLT) Phase II: Progression-free survival at three months | — |
Countries
Germany
Outcome results
None listed