In this phase II multicenter study, the investigators aim to evaluate the efficacy and tolerability of a novel taxane-cabazitaxel as single agent second-line chemotherapy for 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
19
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.
Rambam MC
Haifa, Israel
Rabin Medical Center
Petah Tikva, Israel
Response rate
The primary end point is objective response rate (ORR): CR+ PR, assessed according to response evaluation criteria in solid tumors (RECIST 1.1) guidelines.
Time frame: up to 2 years
Clinical benefit
Secondary endpoints include clinical benefit with the following parameters: PR+CR+SD.
Time frame: up to 2 years
Duration of response
Assessment of duration of response to treatment with Cabazitaxel.
Time frame: up to 2 years
Disease control rate
Assessment of stable disease ≥ 16 weeks, PR or CR.
Time frame: up to 2 years
PFS
To determine the progression free survival (PFS) of study population defined as a 20% increase in the largest diameter of the largest lesion by CT scan.
Time frame: up to 2 years
Overall Survival
To determine the percentage of patients alive at data cutoff from trial entry. Overall survival will be measured from date of randomization to date of death due to any cause.
Time frame: up to 2 years
Safety and tolerability of treatment
Number of participants with adverse events as a measure of safety and tolerability, assessment of dose modifications according to patient's toxicity levels.
Time frame: up to 2 years
Surrogate markers to cabazitaxel
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Assessment of surrogate markers to cabazitaxel response.
Time frame: up to 3 years