This is a phase II/III, multicenter, randomized study which includes 420 patients on six years + 3 years follow up. 92 patients will be included during the phase II ; additional 328 patients will be included. Patients with an advanced or metastatic urothelial cancer with impaired renal function will be randomized in one of the two following chemotherapy arm: * Fractionated Cisplatin + Gemcitabine. * Carboplatin + Gemcitabine. The main objective of the part II study will be to evaluate the efficacy and the safety of a chemotherapy with a doublet platinum salt compound/Gemcitabine with fractionated Cisplatin or Carboplatin in this population. The main objective of the part III study will be to compare the efficacy in terms of overall survival of a chemotherapy with a doublet platinum salt/Gemcitabine with fractionated Cisplatin or Carboplatin in this population.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
46
Carboplatin AUC (area under curve) 4,5 at day 1 of each cycle until 6 cycles.
Cisplatin 35mg/m² at day 1 and day 8 of each cycle until 6 cycles.
Gemcitabine 1000mg/m² at day 1 and day 8 of each cycle until 6 cycles.
INSTITUT DE CANCEROLOGIE DE L'OUEST - Site Paul Papin
Angers, France
Chru Besancon - Hopital Jean Minjoz
Besançon, France
Institut Bergonie
Bordeaux, France
Centre Francois Baclesse
Caen, France
Centre Georges Francois Leclerc
Dijon, France
CH VERSAILLES - Hôpital André Mignot
Le Chesnay, France
CHU LIMOGES - Hôpital Dupuytren
Limoges, France
Centre Leon Berard
Lyon, France
Institut Paoli Calmettes
Marseille, France
Ch Mont de Marsan
Mont-de-Marsan, France
...and 8 more locations
Phase II: Efficacy - Rate of non progression at the end of treatment (C6D21).
Progression is defined according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria V1.1.
Time frame: 5 years.
Phase III: Overall survival (in months).
Overall survival is defined as the time from randomization until death or last follow up news (censured data).
Time frame: 9 years.
Phase II: Tolerance - Percentage of patients for whom at least one of the 3 defined tolerance criteria (see description) is observed.
Defined tolerance criteria : * Postponement of chemotherapy \> or = 2 weeks. * Alteration of renal function. * Need to decrease twice Gemcitabine dose on day 1 for : NCI CTC (National Cancer Institut Common Toxicity Criteria) grade III or IV non-hematologic toxicity, hematologic toxicity.
Time frame: 5 years.
Phase II and III: Objective response.
Objective response (ie complete or partial response) will be evaluated according to RECIST v1.1 criteria.
Time frame: Phase II: 5 years ; Phase III: 9 years.
Phase II and III: Tolerance according to NCI toxicity scale (version 4.0).
Time frame: Phase II: 5 years ; Phase III: 9 years.
Phase II and III: Geriatric evaluation using questionnaires.
The geriatric assessment will be evaluate using the following questionnaires: G8 (oncodage) , ADL (activity of daily living), CIRSG (cumulating illness rating scale geriatric) , MMS (mini-mental score), IADL (instrumental activities of daily living), GDS (geriatric depression scale), MNA (mini-nutritional assessment).
Time frame: Phase II: 5 years ; Phase III: 9 years.
Phase II and III: Quality of life using the EORTC QLQ - C30 questionnaire (European Organization for research and treatment of Cancer - Quality of life questionnaire).
Time frame: Phase II: 5 years ; Phase III: 9 years.
Phase II and III: Pharmacokinetics - Platin concentrations
Time frame: At cycles 1 and 2 day 1 - 5 mn before the end of infusion, one hour after the end of infusion, 3 hours (arm A) or 4 hours (arm B) after the end of infusion.
Phase II and III: Pharmacogenetics, exploration of cytidine deaminase activity and study of its genetic polymorphisms.
Time frame: Prior to the initial dose on cycle 1 day 1.
Phase II and III: Progression free survival.
Progression free survival will be evaluated according to RECIST v1.1 criteria.
Time frame: Phase II: 5 years ; phase III: 9 years.
Phase II and III: Overall survival.
Overall survival is defined as the time from randomization until death from all causes combined.
Time frame: Phase II: 5 years ; Phase III: 9 years.
Phase II and III: Time to treatment failure.
Time to treatment failure is defined as the time from randomization to treatment discontinuation, whatever its cause.
Time frame: Phase II: 5 years ; Phase III: 9 years.
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