Clinical trial NCT02240017: A Study Evaluating Chemotherapy With Fractionated Cisplatin/Gemcitabine Versus Carboplatin/Gemcitabine in the Treatment of Advanced or Metastatic Urothelial Cancer With Impaired Renal Function.
Official title: Randomized, Multicenter, Phase II/III Study, Evaluating Fractionated Cisplatin Chemotherapy/Gemcitabine Versus Carboplatin/Gemcitabine in the Treatment of Advanced or Metastatic Urothelial Cancer With Impaired Renal Function.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Advanced Urothelial Cancer
Metastatic Urothelial Cancer
Keywords: Urothelial cancer, renal function impaired.
Lead sponsor: Institut Claudius Regaud
Sponsor class: OTHER
First posted: 2014-09-15
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. . Age \< or = 18 years, patients aged 75 years or more will benefit from a geriatric assessment.
2. . Advanced or metastatic urothelial cancer confirmed histologically or cytologically.
3. . Patients liable to receive a first -line chemotherapy for advanced or metastatic urothelial carcinoma.
4. . Measurable disease according to RECIST criteria V1.1.
5. . Patients who received neoadjuvant or adjuvant chemotherapy based on platinum salt must have completed treatment at least 6 months before entering the study.
6. . Performance status \< or = 2.
7. . Life expectancy \> 3 months.
8. . Patients with creatinine clearance between 40 and 60 ml / min ( according to Cockcroft and Gault ).
9. . Patients having no contra-indication to overhydration.
10. . Satisfactory hematological tests: Neutrophils \> 1.5 G / l Platelets \> 150 G / l , hemoglobin ≥ 10 g / dl.
11. . 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).
12. . In case of prior radiotherapy, a minimum of 14 days must relapse between the end of radiotherapy and study entry.
13. . 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.
14. . Patient affiliated to a social security system in France.
15. . Patient signed informed consent before inclusion in the study and before any specific procedure for the study.

Exclusion Criteria:

1. . Any concomitant or previous malignancy within 5 years prior to the study ( with the exception of basal cell or squamous cell carcinoma in situ).
2. . Pregnant or lactating women.
3. . Patients with brain metastases or meningeal or symptoms suggestive of such secondary locations.
4. . 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 ).
5. . Other concomitant cancer (radiation therapy, radiopharmaceutical agent chemotherapy).
6. . Patients with uncontrolled infection.
7. . Patients with peripheral neuropathy grade\> 1, whatever the origin or patients with hearing loss.
8. . Patient with unstable disease (eg: unstable diabetes, poorly controlled hypertension , congestive heart failure or myocardial infarction within 3 months prior to study entry).
9. . Known hypersensitivity to study drugs.
10. . Treatment with any other investigational drug within 30 days before inclusion.
11. . Any psychological condition , familial, sociological or geographical not to comply with medical monitoring and / or procedures in the study protocol.
12. . Patient protected by law.

Primary outcomes:
measure: Phase II: Efficacy - Rate of non progression at the end of treatment (C6D21).
timeFrame: 5 years.
measure: Phase III: Overall survival (in months).
timeFrame: 9 years.
measure: Phase II: Tolerance - Percentage of patients for whom at least one of the 3 defined tolerance criteria (see description) is observed.
timeFrame: 5 years.
Secondary outcomes:
measure: Phase II and III: Objective response.
timeFrame: Phase II: 5 years ; Phase III: 9 years.
measure: Phase II and III: Tolerance according to NCI toxicity scale (version 4.0).
timeFrame: Phase II: 5 years ; Phase III: 9 years.
measure: Phase II and III: Geriatric evaluation using questionnaires.
timeFrame: Phase II: 5 years ; Phase III: 9 years.
measure: 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).
timeFrame: Phase II: 5 years ; Phase III: 9 years.
measure: Phase II and III: Pharmacokinetics - Platin concentrations
timeFrame: 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.
measure: Phase II and III: Pharmacogenetics, exploration of cytidine deaminase activity and study of its genetic polymorphisms.
timeFrame: Prior to the initial dose on cycle 1 day 1.
measure: Phase II and III: Progression free survival.
timeFrame: Phase II: 5 years ; phase III: 9 years.
measure: Phase II and III: Overall survival.
timeFrame: Phase II: 5 years ; Phase III: 9 years.
measure: Phase II and III: Time to treatment failure.
timeFrame: Phase II: 5 years ; Phase III: 9 years.
Other outcomes:
Locations:
city: Angers
country: France
facility: INSTITUT DE CANCEROLOGIE DE L'OUEST - Site Paul Papin
city: Besançon
country: France
facility: Chru Besancon - Hopital Jean Minjoz
city: Bordeaux
country: France
facility: Institut Bergonie
city: Caen
country: France
facility: Centre Francois Baclesse
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Le Chesnay
country: France
facility: CH VERSAILLES - Hôpital André Mignot
city: Limoges
country: France
facility: CHU LIMOGES - Hôpital Dupuytren
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Mont de Marsan
country: France
facility: Ch Mont de Marsan
city: Montpellier
country: France
facility: Institut Regional Du Cancer Montpellier
city: Paris
country: France
facility: Ap-Hp-Hopital Saint-Louis
city: Saint-Herblain
country: France
facility: INSTITUT DE CANCEROLOGIE DE L'OUEST - Site René Gauducheau
city: Saint-Priest en Jarez
country: France
facility: Institut de Cancerologie Lucien Neuwirth
city: Strasbourg
country: France
facility: CHU de STRASBOURG
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Tours
country: France
facility: Chru Tours
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Institut Claudius Regaud
name: Loic MOUREY, MD
role: STUDY_CHAIR
References: