Methotrexate, Vinblastine, Doxorubicin and Cisplatin (MVAC) Followed by Gemcitabine Plus Cisplatin (GEM+CDDP) in Locally Advanced or Metastatic Bladder Cancer

Study Overview
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Brief Summary
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This phase II trial will study the effectiveness and toxicity of sequential high dose MVAC followed by gemcitabine and cisplatin, as first line treatment in patients with locally advanced or metastatic bladder cancer.

Detailed Description
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High dose MVAC and Cisplatin/Gemcitabine combination regimens have shown comparable efficacy in the first line treatment of advanced or metastatic bladder cancer, whereas the latter regimen has better tolerability. The efficacy and tolerability of the sequential administration of these two regimens is not known.

Official Title
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Sequential High Dose MVAC (Methotrexate, Vinblastine, Doxorubicin and Cisplatin), Followed by Gemcitabine Plus Cisplatin in Treating Patients With Locally Advanced or Metastatic Bladder Cancer

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: Methotrexate
* Drug: Vinblastine
* Drug: Doxorubicin
* Drug: Cisplatin
* Drug: Cisplatin
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed transitional cell carcinoma of the urinary bladder. Metastatic or locally advanced disease. No prior chemotherapy. Performance status (World Health Organization) 0-2. Measurable or evaluable disease. Measurable disease is defined as at least 1 unidimensional measurable lesion ≥20 mm by conventional techniques or 1 bidimensionally measurable lesion ≥ 20 X 10 mm. Lesions that are smaller or uni- or bidimensionally unmeasurable are considered as evaluable disease. Adequate liver (bilirubin ≤ 1.5 Upper Normal Limit, serum glutamate-pyruvate aminotransferase/serum glutamic pyruvic transaminase ≤ 2 Upper Normal Limit, ALP ≤ 2.5 Upper Normal Limit), renal (creatinine ≤ 1.5 Upper Normal Limit) and bone marrow (absolute neutrophil count ≥ 1,500/mm3, platelet count ≥ 100,000/mm3) function. Life expectancy > 3 months. Patients must be able to understand the nature of this study and give written informed consent. Exclusion Criteria: History of serious cardiac disease (unstable angina, severe congestive heart failure, myocardial infarction within the previous 6 months, ventricular arrhythmias). Second primary malignancy, except for non-melanoma skin cancer and in situ cervical cancer. Active infection. Uncontrolled inflammation. Pregnant or lactating women. Psychiatric illness or social situation that would preclude study compliance.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>MVAC -> GEM+CDDP | Drug: Methotrexate<br>* Methotrexate intravenous (IV) 30 mgr/m2 on day 1 every 2 weeks for 6 courses<br>Drug: Vinblastine<br>* Vinblastine IV 3 mgr/m2 on day 1 every 2 weeks for 6 courses<br>Drug: Doxorubicin<br>* Doxorubicin IV 30 mgr/m2 on day 2 every 2 weeks for 6 courses<br>Drug: Cisplatin<br>* Cisplatin IV 70 mgr/m2 on day 2 every 2 weeks for 6 courses<br>* Other names: CDDP;Drug: Cisplatin<br>* Cisplatin IV 70 mgr/m2 on day 1 every 3 weeks for 4 courses<br>* Other names: CDDP;Drug: Gemcitabine<br>* Gemcitabine 1000 mgr/m2 on days 1 and 8 every 3 weeks for 4 courses<br>* Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate |  | Objective responses confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) (on 3rd and 6th cycle) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to tumor progression |  | 1-year | 
| Overall survival |  | 1-year | 
| Toxicity profile |  | Toxicity assessment on each chemotherapy cycle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bladder Cancer