Due to limited experience with cabazitaxel in TCCU, the study will be started as a randomised phase II study. The aim of the phase II study is to evaluate if the response rates (CR + PR) are sufficiently high to further study the treatment regimens in a phase III setting.
Once it is confirmed that the subjects fulfil the eligibility criteria and have signed the informed consent, they will be randomised to receive treatment based on cabazitaxel or vinflunine according to the following study schema: (Randomize 1:1) * Cabazitaxel 25 mg/m2 q3w * Vinflunine 250-320 mg/m2 q3w Random assignment of treatment will be stratified by the presence of 0 versus 1 of the following unfavourable prognostic risk factors proposed recently by Bellmunt et al. (1): * Eastern Cooperative Oncology Group (ECOG) PS 1. * Anaemia with Hb \<10 g/dL. * Presence of liver metastases. All patients enrolled in the study will receive a cycle of treatment with the study medication (cabazitaxel or vinflunine) every 21 days until disease progression or intolerable/unacceptable toxicity. Tumour evaluations will be scheduled every 6 weeks until progression
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
372
Cabazitaxel, to be given intravenously once every 21 days, starting at a dose of 25 mg/m2 as a 1-hour intravenous infusion.
Vinflunine, to be given intravenously once every 21 days, as a 20 minute intravenous infusion, starting at a dose of: * 320 mg/m2 in patients aged ≤75 years with PS 0 and no prior pelvic radiation, and of * 280 mg/m2 in patients aged \>75 - ≤80 years or with PS 1 or prior pelvic radiation, * 250 mg/m2 in patients aged \>80 years.
NKI-AvL
Amsterdam, Amsterdam, Netherlands
RECRUITINGPhase II main objective: to assess the efficacy of cabazitaxel compared to vinflunine in terms of improved objective response rate (ORR) of subjects with metastatic or locally advanced previously treated TCCU.
Efficacy of cabazitaxel compared to vinflunine on terms of improved objective response rate (ORR)
Time frame: From date of randomization to disease progression or until 18 months from enrolment.
Phase III main objective: To assess the efficacy of cabazitaxel compared to vinflunine in terms of improved overall survival (OS) of subjects with metastatic or locally advanced, previously treated TCCU.
Time frame: From date of randomization to death from any cause or until 18 months from enrolment.
Phase II secondary objective: to assess the efficacy of cabazitaxel compared to vinflunine in terms of improved progression-free survival (PFS) and overall survival (OS).
Time frame: From randomisation to either documented disease progression or death from any cause or until 18 months from enrolment (whichever occurs earlier)
Phase II secondary objective: safety profile and tolerability of cabazitaxel. It will be determined from the number of Adverse Events reported.
Time frame: From the date the informed consent is signed up to 30 days after the last dose.
Phase III secondary objective: to assess the efficacy of cabazitaxel compared to vinflunine in terms of improved objetive response rate (ORR) and progression free survival (PFS).
Time frame: From randomisation to either documented disease progression or death from any cause or until 18 months from enrolment (whichever occurs earlier)
Phase III secondary objective: safety profile and tolerability of cabazitaxel. It will be determined from the number of Adverse Events reported.
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Vumc Amsterdam
Amsterdam, Amsterdam, Netherlands
NOT_YET_RECRUITINGSt. Antoniusziekenhuis
Nieuwegein, Nieuwegein, Netherlands
RECRUITINGErasmus MC Rotterdam
Rotterdam, Netherlands
RECRUITINGComplejo Hospitalario Universitario A Coruña
A Coruña, A Coruña, Spain
RECRUITINGCentro Oncologico de Galica
A Coruña, A Coruña, Spain
RECRUITINGHospital Clínico Universitario de Santiago
Santiago de Compostela, A Coruña, Spain
RECRUITINGHospital General Universitario de Elche
Elche, Alicante, Spain
RECRUITINGHospital del Mar
Barcelona, Barcelona, Spain
RECRUITINGHospital Vall d´Hebron
Barcelona, Barcelona, Spain
RECRUITING...and 10 more locations
Time frame: From the date the informed consent is signed up to 30 days after the last dose.