A Single Arm, Multicenter, Open-label Phase II Trial of Cabazitaxel as Second Line Treatment of Patients With Locally Advanced or Metastatic Urothelial Carcinoma
For those patients with advanced bladder cancer who have progressed on a platinum based
regimen, no widely accepted standard second line therapy currently exists. Taxanes including
paclitaxel and docetaxel have exhibited limited clinical activity in this disease and are
sometimes given off study. Cabazitaxel is a novel semi-synthetic taxane with a low affinity
for the multidrug resistance 1 protein. In cell lines cabazitaxel is as potent as docetaxel,
but in tumor cells that are resistant to taxanes, cabazitaxel overcome taxanes resistance.
In recent clinical data, this drug was shown to have potent activity in patients with
metastatic prostate cancer resistant to docetaxel. Based on this phase III data, cabazitaxel
was recently approved in the US, Europe and in Israel for these patients. The main toxicity
of this taxane is neutropenia and diarrhea, thus primary prevention with GCSF may reduce the
main toxicity of this agent.
In this phase II multicenter study, the investigators aim to evaluate the efficacy and
tolerability of this novel taxane -cabazitaxel as single agent second-line chemotherapy for
metastatic urothelial carcinoma after failure of prior platinum-based chemotherapy.
The patients are planned to receive cabazitaxel at a starting dose of 25 mg/m(2)
intravenously over 1 h, following premedication as accepted with cabazitaxel. Treatment
cycles are every 3 weeks. All patients will receive primary GCSF support.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The primary end point is objective response rate (ORR): CR+ PR, assessed according to response evaluation criteria in solid tumors (RECIST 1.1) guidelines.
May-2014 (up to 2 years)
Avivit - Pe'er, Dr.
Israel: Ministry of Health