First-Line Treatment of Advanced Bladder Cancer Randomized vs. Gemcitabine ± Vinflunine in Patients Ineligible to Receive Cisplatin-Based Therapy

Study Overview
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Brief Summary
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The purpose of this study is to test an investigational drug, vinflunine (BMS-710485), in combination with gemcitabine in patients with Transitional Cell Carcinoma who cannot be treated with cisplatin. This study will help to determine whether vinflunine in combination with gemcitabine will extend the time period until further growth of the tumor more than gemcitabine alone.

Official Title
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A Multicenter, Randomized Double-Blind Phase II/III Study in the First-Line Treatment of Advanced Transitional Cell Carcinoma (TCC) of the Urothelium Comparing Vinflunine/Gemcitabine to Placebo/Gemcitabine in Patients Who Are Ineligible to Receive Cisplatin-Based Therapy

Conditions
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Bladder Cancer, Transitional Cell Carcinoma, Metastasis

Intervention / Treatment
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* Drug: Vinflunine
* Drug: Gemcitabine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of transitional cell carcinoma of the urothelium that is locally advanced or metastatic Ineligible for cisplatin-based therapy because of at least one of the following two medical conditions: Calculated creatinine clearance ≤60 mL/min: OR New York Heart Association Classification Stage III-IV Congestive Heart Failure Measurable disease documented by imaging with at least one uni-dimensional lesion Adequate performance status (ECOG 0, 1, or 2) Men and women ≥18 years of age Exclusion Criteria: Patients in whom radiation or surgery is indicated Current neuropathy ≥ CTCAE grade 3 Prior radiation to ≥ 30% of bone marrow Inadequate renal function: serum creatinine clearance ≤ 20 mL/min Prior allergy to any vinca alkaloid

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vinflunine and gemcitabine<br>solution for injection, IV, vinflunine: 280/320 mg/m2 + gemcitabine: 1000 mg/m2, every 3 wks, variable duration | Drug: Vinflunine<br>* solution for injection, IV, vinflunine: 280/320 mg/m2 + gemcitabine: 1000 mg/m2, every 3 wks, variable duration<br>Drug: Gemcitabine<br>* solution for injection, IV, placebo + gemcitabine, 1000 mg/m2, every 3 wks, variable duration<br>|
| Placebo Comparator: placebo and gemcitabine<br>solution for injection, IV, placebo + gemcitabine, 1000 mg/m2, every 3 wks, variable duration | Drug: Gemcitabine<br>* solution for injection, IV, placebo + gemcitabine, 1000 mg/m2, every 3 wks, variable duration<br>Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Progression-free Survival (PFS) as Defined by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria in Participants With Advanced Transitional Cell Carcinoma (TCC) of the Urothelium | PFS survival is defined as the time between randomization and the date of progression or death, whichever occurs first, before or after treatment discontinuation. For those still on study and those who remain alive and have not progressed after treatment discontinuation, PFS will be censored on the date of the last tumor assessment. | Until tumor progression, unacceptable toxicity, withdrawal of patient consent, or discontinuation by investigator decision | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response Rate in Participants With A Best Response of Complete (CR) or Partial (PR) as Defined by RECIST criteria | Tumor response rate is defined as the number of participants in that arm whose best response is PR or CR, divided by the total number of randomized participants in the arm. | Until tumor progression, unacceptable toxicity, withdrawal of patient consent, or discontinuation by investigator decision | 
| Overall Survival of Participants With TCC of the Urothelium | Survival duration is defined as the time (in months) from randomization until death. For those participants who have not died, survival duration will be censored at the last date the participant was known to be alive. | Until tumor progression, unacceptable toxicity, withdrawal of patient consent, or discontinuation by investigator decision | 
| Disease Control Rate in Participants With Best Response of CR, PR, or Stable Disease (SD) | Disease control rate is defined as the number of participants in that arm whose best response is PR, CR, or SD, divided by the total number of randomized participants in the treatment arm. | Until tumor progression, unacceptable toxicity, withdrawal of patient consent, or discontinuation by investigator decision | 
| Duration of Response in Participants With Best Response of CR or PR | Duration of response is computed for participants with best response of CR or PR; the duration is measured from the time measurement criteria are met for CR or PR, whichever is recorded first, until the date of documented progressive disease or death. Participants who neither relapse nor die will be censored on the date of their last tumor assessment. | Until tumor progression, unacceptable toxicity, withdrawal of patient consent, or discontinuation by investigator decision | 
| Number of Participants With Outcome of Death, Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Discontinuation | An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in drug dependency or drug abuse, or is an important medical event. | Until tumor progression, unacceptable toxicity, withdrawal of patient consent, or discontinuation by investigator decision | 
| Number of Participants With Serum Chemistry Abnormalities by Worst Common Terminology Criteria (CTC) Grade |  | Following Day 1 to no longer than 30 days after last dose of study medication | 
| Number of Participants With Abnormal Laboratory Findings by Worst CTC Grade |  | Following Day 1 to no longer than 30 days after last dose of study medication | 
| Time to Response in Participants With Best Response of CR or PR | Time to response is defined as the number of months from the first dose of study therapy until measurement criteria are met for PR or CR, whichever is recorded first. | Until tumor progression, unacceptable toxicity, withdrawal of patient consent, or discontinuation by investigator decision | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced or metastatic transitional cell carcinoma of the urothelium