Advanced Urothelial Cancer of Bladder After Failure of Platinum-containing Therapy. Clinical Trial
Official title:
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).
n/a
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment