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Target-specific Therapy With Pazopanib as Add-on to Vinflunine in Patients With Advanced or Metastatic Urothelial Carcinoma of the Bladder After Failure of Platinum-based Treatment
Urothelial carcinoma of the bladder mostly is chemically induced and represents the second prevalent urooncological disease. About 20% of newly diagnosed urothelial carcinoma cases of the bladder are already advanced or metastasized. Before 2008 2009 no second line therapy after failure of primary systemic therapy of advanced / metastatic disease was established outside of clinical trials. The actual standard for this situation was a supportive, symptomatic therapy. Vinflunine has demonstrated improved survival from 4.3 to 6.9 months (p=0.04), with an adequate disease control, good symptom control and with acceptable toxicity. Based on these results, this compound became standard se¬cond line treatment for refractory metastatic bladder cancer disease after failure of platinum-containing therapy. As the prognosis still remains poor, new treatment opportunities have to be explored. The target-specific therapy with Pazopanib suggests a positive influence of both inductive and perioperative treatment of solid tumors. Pazopanib has been approved by the FDA and the EMA for the treatment of advance renal cell carcinoma. Results for advanced urothelial carcinoma are missing so far as well as data on tolerability of the combination of both vinflunine and pazopanib. As the pharmacodynamic properties as well as the safety profile of both drugs are different, assumption is justified that there might occur additive efficacy effects without addition of adverse outcomes. Aim of the study thus is 1. To define the maximum tolerated dose (MTD) of Pazopanib in combination with Vinflunine in a phase-I-setting and 2. To further assess efficacy and safety of the combination at the MTD level in phase II. During the pase-I-part of the study different doses of pazopanib will be added to the standard vinflunine scheme in groups of 6 patients maximum. Dose escalation will only be performed in the next patient group if not more than one out of six patients shows dose-limiting toxicity. Each patient will be treated with the drug combination for a duration of two vinflunine cycles, that is six weeks. During the phase-II study new patients will be treated with the drug combination at maximum-tolerated dose until disease progression (assessed by RECIST 1.1 procedures).
Details
| Lead sponsor | Prof. Dr. Thomas Otto |
|---|---|
| Phase | Phase 1/Phase 2 |
| Status | COMPLETED |
| Enrolment | 5 |
| Start date | 2011-03 |
| Completion | 2012-08 |
Conditions
- Advanced Urothelial Cancer of Bladder After Failure of Platinum-containing Therapy.
Interventions
- Pazopanib as add-on to vinflunine
Primary outcomes
- Phase I: Definition of the Maximum Tolerated Dose (MTD) of Pazopanib in combination with Vinflunine. — 6 weeks (two cycles of vinflunine)
MTD ist defined as the dose level with dose-limiting toxicity occurring in maximum one out of six patients. - Phase II: Progression-free survival rate — 3 months
Progression-free survival will be assessed by means of RECIST 1.1. methodology
Countries
Germany