A Study Evaluating Chemotherapy With Fractionated Cisplatin/Gemcitabine Versus Carboplatin/Gemcitabine in the Treatment of Advanced or Metastatic Urothelial Cancer With Impaired Renal Function.

NCT ID: NCT02240017

Last Updated: 2019-08-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-21
• Study Completion Date: 2019-07-15

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.

Conditions

Advanced Urothelial Cancer; Metastatic Urothelial Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Carboplatin/Gemcitabine

Group Type: ACTIVE_COMPARATOR

Carboplatin

Intervention Type: DRUG

Carboplatin AUC (area under curve) 4,5 at day 1 of each cycle until 6 cycles.

Gemcitabine

Intervention Type: DRUG

Gemcitabine 1000mg/m² at day 1 and day 8 of each cycle until 6 cycles.

Fractionated Cisplatin/Gemcitabine

Group Type: EXPERIMENTAL

Fractionated Cisplatin

Intervention Type: DRUG

Cisplatin 35mg/m² at day 1 and day 8 of each cycle until 6 cycles.

Gemcitabine

Intervention Type: DRUG

Gemcitabine 1000mg/m² at day 1 and day 8 of each cycle until 6 cycles.

Interventions

Carboplatin

Carboplatin AUC (area under curve) 4,5 at day 1 of each cycle until 6 cycles.

Intervention Type: DRUG

Fractionated Cisplatin

Cisplatin 35mg/m² at day 1 and day 8 of each cycle until 6 cycles.

Intervention Type: DRUG

Gemcitabine

Gemcitabine 1000mg/m² at day 1 and day 8 of each cycle until 6 cycles.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut Claudius Regaud

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Loic MOUREY, MD

Role: STUDY_CHAIR

Institut Claudius Regaud

Locations

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

Institut Regional Du Cancer Montpellier

Montpellier, , France

Ap-Hp-Hopital Saint-Louis

Paris, , France

INSTITUT DE CANCEROLOGIE DE L'OUEST - Site René Gauducheau

Saint-Herblain, , France

Institut de Cancerologie Lucien Neuwirth

Saint-Priest-en-Jarez, , France

CHU de STRASBOURG

Strasbourg, , France

Institut Claudius Regaud

Toulouse, , France

Chru Tours

Tours, , France

Institut Gustave Roussy

Villejuif, , France

Countries

France

Other Identifiers

13 URO 02

Identifier Type: -

Identifier Source: org_study_id