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

Metastatic Urothelial Cancer Clinical Trial

— VEFORA  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02240017
• Other study ID #: 13 URO 02
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: January 21, 2015
• Est. completion date: July 15, 2019

Study information

• Verified date: August 2019
• Source: Institut Claudius Regaud
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: July 15, 2019
• Est. primary completion date: April 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Urothelial Cancer
• Metastatic Urothelial Cancer
• Renal Insufficiency

Intervention

Drug:
• Carboplatin
Carboplatin AUC (area under curve) 4,5 at day 1 of each cycle until 6 cycles.
• Fractionated Cisplatin
Cisplatin 35mg/m² at day 1 and day 8 of each cycle until 6 cycles.
• Gemcitabine
Gemcitabine 1000mg/m² at day 1 and day 8 of each cycle until 6 cycles.

Locations

Country	Name	City	State
France	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

Sponsors (1)

Lead Sponsor	Collaborator
Institut Claudius Regaud

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	5 years.
Primary	Phase III: Overall survival (in months).	Overall survival is defined as the time from randomization until death or last follow up news (censured data).	9 years.
Primary	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.	5 years.
Secondary	Phase II and III: Objective response.	Objective response (ie complete or partial response) will be evaluated according to RECIST v1.1 criteria.	Phase II: 5 years ; Phase III: 9 years.
Secondary	Phase II and III: Tolerance according to NCI toxicity scale (version 4.0).		Phase II: 5 years ; Phase III: 9 years.
Secondary	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).	Phase II: 5 years ; Phase III: 9 years.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	Phase II and III: Progression free survival.	Progression free survival will be evaluated according to RECIST v1.1 criteria.	Phase II: 5 years ; phase III: 9 years.
Secondary	Phase II and III: Overall survival.	Overall survival is defined as the time from randomization until death from all causes combined.	Phase II: 5 years ; Phase III: 9 years.
Secondary	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.	Phase II: 5 years ; Phase III: 9 years.