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

• Sponsor: Institut Claudius Regaud (Other)
• Overall Status: Completed
• CT.gov ID: NCT02240017
• Collaborator: (none)
• Enrollment: 46
• Locations: 18
• Arms: 2
• Actual Duration (Months): 53.7
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Urothelial Cancer; Metastatic Urothelial Cancer	Drug: Carboplatin; Drug: Fractionated Cisplatin; Drug: Gemcitabine	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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.
• Actual Study Start Date: Jan 21, 2015
• Actual Primary Completion Date: Apr 10, 2018
• Actual Study Completion Date: Jul 15, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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).

3. 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

1. 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.

2. Phase II and III: Tolerance according to NCI toxicity scale (version 4.0). [Phase II: 5 years ; Phase III: 9 years.]

3. 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).

4. 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.]

5. 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.]

6. 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.]

7. 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.

8. 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.

9. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	INSTITUT DE CANCEROLOGIE DE L'OUEST - Site Paul Papin	Angers		France	49933
2	Chru Besancon - Hopital Jean Minjoz	Besançon		France	25030
3	Institut Bergonie	Bordeaux		France	33076
4	Centre Francois Baclesse	Caen		France	14076
5	Centre Georges Francois Leclerc	Dijon		France	21079
6	CH VERSAILLES - Hôpital André Mignot	Le Chesnay		France	78157
7	CHU LIMOGES - Hôpital Dupuytren	Limoges		France	87042
8	Centre Leon Berard	Lyon		France	69373
9	Institut Paoli Calmettes	Marseille		France	13273
10	Ch Mont de Marsan	Mont de Marsan		France	40024
11	Institut Regional Du Cancer Montpellier	Montpellier		France	34298
12	Ap-Hp-Hopital Saint-Louis	Paris		France	75010
13	INSTITUT DE CANCEROLOGIE DE L'OUEST - Site René Gauducheau	Saint-Herblain		France	44805
14	Institut de Cancerologie Lucien Neuwirth	Saint-Priest en Jarez		France	42271
15	CHU de STRASBOURG	Strasbourg		France	67091
16	Institut Claudius Regaud	Toulouse		France	31052
17	Chru Tours	Tours		France	37044
18	Institut Gustave Roussy	Villejuif		France	94805

Sponsors and Collaborators

• Institut Claudius Regaud

Investigators

• Study Chair: Loic MOUREY, MD, Institut Claudius Regaud

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Institut Claudius Regaud
• ClinicalTrials.gov Identifier: NCT02240017
• Other Study ID Numbers: 13 URO 02
• First Posted: Sep 15, 2014
• Last Update Posted: Aug 9, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by Institut Claudius Regaud: Urothelial cancer, renal function impaired.
• Additional relevant MeSH terms: Renal Insufficiency; Gemcitabine; Carboplatin

Study Results

No Results Posted as of Aug 9, 2019