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

• Tumor Response Rate in Participants With A Best Response of Complete (CR) or Partial (PR) as Defined by RECIST criteria [ Time Frame: Until tumor progression, unacceptable toxicity, withdrawal of patient consent, or discontinuation by investigator decision ] [ Designated as safety issue: No ]
  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.
• Overall Survival of Participants With TCC of the Urothelium [ Time Frame: Until tumor progression, unacceptable toxicity, withdrawal of patient consent, or discontinuation by investigator decision ] [ Designated as safety issue: No ]
  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.
• Disease Control Rate in Participants With Best Response of CR, PR, or Stable Disease (SD) [ Time Frame: Until tumor progression, unacceptable toxicity, withdrawal of patient consent, or discontinuation by investigator decision ] [ Designated as safety issue: No ]
  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.
• Duration of Response in Participants With Best Response of CR or PR [ Time Frame: Until tumor progression, unacceptable toxicity, withdrawal of patient consent, or discontinuation by investigator decision ] [ Designated as safety issue: No ]
  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.
• Number of Participants With Outcome of Death, Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Discontinuation [ Designated as safety issue: Yes ]
  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.
• Number of Participants With Serum Chemistry Abnormalities by Worst Common Terminology Criteria (CTC) Grade [ Time Frame: Following Day 1 to no longer than 30 days after last dose of study medication ] [ Designated as safety issue: Yes ]
• Number of Participants With Abnormal Laboratory Findings by Worst CTC Grade [ Time Frame: Following Day 1 to no longer than 30 days after last dose of study medication ] [ Designated as safety issue: Yes ]
• Time to Response in Participants With Best Response of CR or PR [ Time Frame: Until tumor progression, unacceptable toxicity, withdrawal of patient consent, or discontinuation by investigator decision ] [ Designated as safety issue: No ]
  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.

• To compare the response rate
• To compare Overall Survival
• To compare disease control rate
• To estimate the duration of response
• To estimate time to response
• To evaluate the safety profile

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.

• Bladder Cancer
• Transitional Cell Carcinoma
• Metastasis

• Drug: vinflunine and gemcitabine
  solution for injection, IV, vinflunine: 280/320 mg/m2 + gemcitabine: 1000 mg/m2, every 3 wks, variable duration
• Drug: placebo and gemcitabine
  solution for injection, IV, placebo + gemcitabine, 1000 mg/m2, every 3 wks, variable duration

• Experimental: 1
  Intervention: Drug: vinflunine and gemcitabine
• Placebo Comparator: 2
  Intervention: Drug: placebo and gemcitabine

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