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Trial record 1 of 1 for:    vefora | France
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A Study Evaluating Chemotherapy With Fractionated Cisplatin/Gemcitabine Versus Carboplatin/Gemcitabine in the Treatment of Advanced or Metastatic Urothelial Cancer With Impaired Renal Function. (VEFORA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02240017
Recruitment Status : Completed
First Posted : September 15, 2014
Last Update Posted : August 9, 2019
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Advanced Urothelial Cancer Metastatic Urothelial Cancer Drug: Carboplatin Drug: Fractionated Cisplatin Drug: Gemcitabine Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
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 : January 21, 2015
Actual Primary Completion Date : April 10, 2018
Actual Study Completion Date : July 15, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Tests

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.




Primary Outcome Measures :
  1. Phase II: Efficacy - Rate of non progression at the end of treatment (C6D21). [ Time Frame: 5 years. ]
    Progression is defined according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria V1.1.

  2. Phase III: Overall survival (in months). [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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). [ Time Frame: Phase II: 5 years ; Phase III: 9 years. ]
  3. Phase II and III: Geriatric evaluation using questionnaires. [ Time Frame: 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). [ Time Frame: Phase II: 5 years ; Phase III: 9 years. ]
  5. Phase II and III: Pharmacokinetics - Platin concentrations [ Time Frame: 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. [ Time Frame: Prior to the initial dose on cycle 1 day 1. ]
  7. Phase II and III: Progression free survival. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02240017


Locations
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Sponsors and Collaborators
Institut Claudius Regaud
Investigators
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Study Chair: Loic MOUREY, MD Institut Claudius Regaud

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Responsible Party: Institut Claudius Regaud
ClinicalTrials.gov Identifier: NCT02240017    
Other Study ID Numbers: 13 URO 02
First Posted: September 15, 2014    Key Record Dates
Last Update Posted: August 9, 2019
Last Verified: August 2019
Keywords provided by Institut Claudius Regaud:
Urothelial cancer, renal function impaired.
Additional relevant MeSH terms:
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Renal Insufficiency
Kidney Diseases
Urologic Diseases
Gemcitabine
Cisplatin
Carboplatin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs