A Study Evaluating Chemotherapy With Fractionated Cisplatin/Gemcitabine Versus Carboplatin/Gemcitabine in the Treatment of Advanced or Metastatic Urothelial Cancer With Impaired Renal Function.
- Conditions
- Advanced Urothelial CancerMetastatic Urothelial Cancer
- Interventions
- Registration Number
- NCT02240017
- Lead Sponsor
- Institut Claudius Regaud
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 46
- . Age < or = 18 years, patients aged 75 years or more will benefit from a geriatric assessment.
- . Advanced or metastatic urothelial cancer confirmed histologically or cytologically.
- . Patients liable to receive a first -line chemotherapy for advanced or metastatic urothelial carcinoma.
- . Measurable disease according to RECIST criteria V1.1.
- . Patients who received neoadjuvant or adjuvant chemotherapy based on platinum salt must have completed treatment at least 6 months before entering the study.
- . Performance status < or = 2.
- . Life expectancy > 3 months.
- . Patients with creatinine clearance between 40 and 60 ml / min ( according to Cockcroft and Gault ).
- . Patients having no contra-indication to overhydration.
- . Satisfactory hematological tests: Neutrophils > 1.5 G / l Platelets > 150 G / l , hemoglobin ≥ 10 g / dl.
- . Satisfactory liver function tests: total bilirubin < 1.5 x ULN (upper limit of normal), AST (aspartate aminotransferase) and ALT (alanine aminotransferase)<or = 2.5 x ULN (or 5 x ULN if liver metastases).
- . In case of prior radiotherapy, a minimum of 14 days must relapse between the end of radiotherapy and study entry.
- . For women of childbearing age , use an effective contraceptive method to study entry and for the duration of the study and 6 months after the last dose of study treatment ; For sexually active fertile men having a partner of childbearing age using effective contraception for the duration of the study and 6 months after the last dose of study treatment.
- . Patient affiliated to a social security system in France.
- . Patient signed informed consent before inclusion in the study and before any specific procedure for the study.
- . Any concomitant or previous malignancy within 5 years prior to the study ( with the exception of basal cell or squamous cell carcinoma in situ).
- . Pregnant or lactating women.
- . Patients with brain metastases or meningeal or symptoms suggestive of such secondary locations.
- . Bisphosphonate or Denosumab treatment initiated within 28 days prior to randomization into the study or patient who have started such treatment during the study ( a bisphosphonate or denosumab treatment initiated within a period longer than 28 days before randomization may be continued without change during the study ).
- . Other concomitant cancer (radiation therapy, radiopharmaceutical agent chemotherapy).
- . Patients with uncontrolled infection.
- . Patients with peripheral neuropathy grade> 1, whatever the origin or patients with hearing loss.
- . Patient with unstable disease (eg: unstable diabetes, poorly controlled hypertension , congestive heart failure or myocardial infarction within 3 months prior to study entry).
- . Known hypersensitivity to study drugs.
- . Treatment with any other investigational drug within 30 days before inclusion.
- . Any psychological condition , familial, sociological or geographical not to comply with medical monitoring and / or procedures in the study protocol.
- . Patient protected by law.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Fractionated Cisplatin/Gemcitabine Gemcitabine - Fractionated Cisplatin/Gemcitabine Fractionated Cisplatin - Carboplatin/Gemcitabine Gemcitabine - Carboplatin/Gemcitabine Carboplatin -
- Primary Outcome Measures
Name Time Method Phase II: Efficacy - Rate of non progression at the end of treatment (C6D21). 5 years. Progression is defined according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria V1.1.
Phase III: Overall survival (in months). 9 years. Overall survival is defined as the time from randomization until death or last follow up news (censured data).
Phase II: Tolerance - Percentage of patients for whom at least one of the 3 defined tolerance criteria (see description) is observed. 5 years. 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.
- Secondary Outcome Measures
Name Time Method Phase II and III: Pharmacogenetics, exploration of cytidine deaminase activity and study of its genetic polymorphisms. Prior to the initial dose on cycle 1 day 1. Phase II and III: Overall survival. Phase II: 5 years ; Phase III: 9 years. Overall survival is defined as the time from randomization until death from all causes combined.
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). Phase II: 5 years ; Phase III: 9 years. Phase II and III: Tolerance according to NCI toxicity scale (version 4.0). Phase II: 5 years ; Phase III: 9 years. Phase II and III: Objective response. Phase II: 5 years ; Phase III: 9 years. Objective response (ie complete or partial response) will be evaluated according to RECIST v1.1 criteria.
Phase II and III: Geriatric evaluation using questionnaires. Phase II: 5 years ; Phase III: 9 years. 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).
Phase II and III: Pharmacokinetics - Platin concentrations 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: Progression free survival. Phase II: 5 years ; phase III: 9 years. Progression free survival will be evaluated according to RECIST v1.1 criteria.
Phase II and III: Time to treatment failure. Phase II: 5 years ; Phase III: 9 years. Time to treatment failure is defined as the time from randomization to treatment discontinuation, whatever its cause.
Trial Locations
- Locations (18)
Centre Francois Baclesse
🇫🇷Caen, France
INSTITUT DE CANCEROLOGIE DE L'OUEST - Site Paul Papin
🇫🇷Angers, France
Chru Besancon - Hopital Jean Minjoz
🇫🇷Besançon, France
Institut Bergonie
🇫🇷Bordeaux, France
Centre Georges Francois Leclerc
🇫🇷Dijon, France
Centre Leon Berard
🇫🇷Lyon, France
CH VERSAILLES - Hôpital André Mignot
🇫🇷Le Chesnay, France
CHU LIMOGES - Hôpital Dupuytren
🇫🇷Limoges, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Ch Mont de Marsan
🇫🇷Mont de Marsan, France
Institut Regional Du Cancer Montpellier
🇫🇷Montpellier, France
INSTITUT DE CANCEROLOGIE DE L'OUEST - Site René Gauducheau
🇫🇷Saint-Herblain, France
Ap-Hp-Hopital Saint-Louis
🇫🇷Paris, France
Institut de Cancerologie Lucien Neuwirth
🇫🇷Saint-Priest en Jarez, France
CHU de STRASBOURG
🇫🇷Strasbourg, France
Chru Tours
🇫🇷Tours, France
Institut Claudius Regaud
🇫🇷Toulouse, France
Institut Gustave Roussy
🇫🇷Villejuif, France