Gene Expression Profiling in Patients With Invasive Bladder Cancer Receiving Methotrexate, Vinblastine, Doxorubicin, and Cisplatin

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as methotrexate, vinblastine, doxorubicin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Evaluating blood or tissue samples from patients with cancer may help doctors learn more about changes that occur in DNA, identify biomarkers related to cancer, and predict how well patients will respond to combination chemotherapy. PURPOSE: This phase II trial is studying gene expression profiling to see how well it works in predicting response to treatment in patients with invasive bladder cancer receiving methotrexate, vinblastine, doxorubicin, and cisplatin.

Detailed Description
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OBJECTIVES: Primary Analyze the correlation between gene expression profile and the effect of chemotherapy and detect the significant cluster of genes useful to predict chemosensitivity. Confirm the reduction in original tumor size in patients with invasive bladder cancer treated with methotrexate, vinblastine, doxorubicin hydrochloride, and cisplatin. Secondary Determine the safety of this regimen in these patients. Determine the overall survival rate in patients treated with this regimen. Assess the reduction in size of metastatic lesions in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive methotrexate on days 1, 15, and 22, vinblastine on days 2, 15, and 22, doxorubicin hydrochloride and cisplatin on day 2. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Patient samples will be collected for gene expression profiling. After completion of study treatment, patients are followed for 3 years.

Official Title
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Phase II Clinical Trial Concerning Gene Expression Profiling to Predict the Chemosensitivity of Invasive Bladder Cancer

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: doxorubicin hydrochloride
* Drug: methotrexate
* Drug: vinblastine
* Genetic: gene expression profiling
* Procedure: neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of invasive bladder cancer Must be confirmed by chest and abdominal CT scan OR pelvic MRI scan and transurethral biopsy (with definitive muscle invasion > T2) within 4 weeks prior to registration PATIENT CHARACTERISTICS: ECOG performance status 0-1 WBC ≥ 3,000/mm^3 Neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Total bilirubin ≤ 1.5 mg/dL Serum creatinine ≤ 1.5 mg/dL AST and ALT ≤ 2.5 x upper limit of normal Not pregnant No liver cirrhosis No ischemic cardiovascular disease or arrhythmia for which treatment is necessary No cardiac infarction within the past 6 months No interstitial pneumonia, pulmonary fibrosis, or any other diseases by which oxygen inhalation therapy is needed No active cancerous lesion other than upper urinary tract tumor No high fever or any other infectious symptom No uncontrolled hypertension or diabetes mellitus PRIOR CONCURRENT THERAPY: No prior systemic chemotherapy

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cisplatin|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: methotrexate|nan|
|Drug: vinblastine|nan|
|Genetic: gene expression profiling|nan|
|Procedure: neoadjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of genes associated with sensitivity to the chemotherapy in tumor size reduction of original bladder tumor |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety |  |  | 
| Overall survival rate |  |  | 
| Size reduction of metastatic lesion |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent bladder cancer, stage II bladder cancer, stage III bladder cancer, stage IV bladder cancer