Neoadjuvant Ifosfamide, Doxorubicin, Gemcitabine, and Cisplatin in Treating Patients Who Are Undergoing Radical Cystectomy for Locally Advanced Carcinoma (Cancer) of the Urothelium

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as ifosfamide, doxorubicin, gemcitabine, and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug, and giving them before surgery, may shrink the tumor so that it can be removed. PURPOSE: This phase II trial is studying how well neoadjuvant combination chemotherapy works in treating patients undergoing radical cystectomy for locally advanced carcinoma of the urothelium.

Detailed Description
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OBJECTIVES: Primary Determine the response rate and 4-year disease-free survival of patients with locally advanced carcinoma of the urothelium undergoing radical cystectomy treated with neoadjuvant chemotherapy comprising ifosfamide, doxorubicin, and gemcitabine followed by cisplatin, gemcitabine, and ifosfamide. Secondary Compare perioperative morbidity and mortality of patients treated with this regimen vs historical standards. OUTLINE: Patients receive neoadjuvant chemotherapy comprising ifosfamide IV over 3 hours on days 1-4, doxorubicin IV on day 3, gemcitabine IV over 30 minutes on days 2 and 4, and filgrastim (G-CSF) subcutaneously on days 7-12 or until blood counts recover. Treatment repeats every 3 weeks for a total of 3 courses. Patients then receive cisplatin IV, gemcitabine IV over 90 minutes, and ifosfamide IV over 30 minutes on day 1. Treatment repeats every 2 weeks for a total of 4-6 courses. Four to six weeks after the completion of all neoadjuvant chemotherapy, patients undergo cystectomy. Patients are followed at 9, 12, 15, 18, 24, and 30 months and then annually thereafter. PROJECTED ACCRUAL: A total of 31-49 patients will be accrued for this study within 16-25 months.

Official Title
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Phase II Trial of Neoadjuvant, Multi-Agent Chemotherapy For Locally Advanced Urothelial Cancer

Conditions
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Bladder Cancer, Transitional Cell Cancer of the Renal Pelvis and Ureter, Urethral Cancer

Intervention / Treatment
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* Biological: filgrastim
* Drug: cisplatin
* Drug: doxorubicin hydrochloride
* Drug: gemcitabine hydrochloride
* Drug: ifosfamide
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed carcinoma of the urothelium, meeting 1 of the following criteria for locally advanced disease: Clinical stage T3b disease, defined by presence of a mass on examination under anesthesia Clinical stage T4a disease, defined by direct invasion of prostatic stroma, vagina, or rectum Lymphovascular invasion on transurethral resection specimen Upper tract disease or micropapillary histology allowed No evidence of disease outside the pelvis PATIENT CHARACTERISTICS: Age Any age Performance status 0-2 Life expectancy Not specified Hematopoietic Bone marrow function adequate Hepatic Liver function adequate Renal Creatinine clearance ≥ 45 mL/min Cardiovascular Ejection fraction ≥ 50% Other Not pregnant No other malignancy likely to be life-threatening within the next 4 years PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery See Disease Characteristics
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

| Intervention/Treatment |
| --- |
|Biological: filgrastim|nan|
|Drug: cisplatin|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: gemcitabine hydrochloride|nan|
|Drug: ifosfamide|nan|
|Procedure: conventional surgery|nan|
|Procedure: neoadjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  | 6 weeks following treatment | 
| Disease-free survival at 4 years |  | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of perioperative treatment morbidity and mortality with historical standards |  | Minimally reviewed following 6 weeks post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III bladder cancer, regional transitional cell cancer of the renal pelvis and ureter, anterior urethral cancer, posterior urethral cancer, urethral cancer associated with invasive bladder cancer