Combination Chemotherapy in Treating Patients With Metastatic or Locally Advanced Bladder Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy in treating patients with metastatic or locally advanced bladder cancer.

Detailed Description
-----------------
OBJECTIVES: Determine the safety and toxicity of doxorubicin, gemcitabine, and filgrastim (G-CSF) followed by ifosfamide, paclitaxel, cisplatin, and G-CSF in patients with metastatic or locally advanced transitional cell carcinoma of the urothelium. Determine the efficacy of this regimen in this patient population. OUTLINE: This is a dose-escalation study of gemcitabine. Patients receive doxorubicin IV over 30 minutes and gemcitabine IV on day 1 and filgrastim (G-CSF) subcutaneously (SC) on days 3-11. Treatment repeats every 2 weeks for 5 courses. After completion of the fifth course, patients receive paclitaxel IV over 3 hours and cisplatin IV over 1 hour on day 1, ifosfamide IV over 1 hour on days 1-3, and G-CSF SC daily on days 6-17. Treatment repeats every 3-4 weeks for 4 courses. Cohorts of 3-6 patients receive escalating doses of gemcitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 3 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at the MTD. PROJECTED ACCRUAL: A maximum of 20 patients will be accrued for phase I and a maximum of 10 patients will be accrued for phase II within 2-3 years.

Official Title
-----------------
Phase I/II Trial of Sequential Doxorubicin/Gemcitabine (AG) and Ifosfamide, Paclitaxel, and Cisplatin (ITP) Chemotherapy (AG-ITP) in Patients With Metastatic or Locally Advanced Transitional Cell Carcinoma of the Urothelium

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

Intervention / Treatment
-----------------
* Biological: filgrastim
* Drug: cisplatin
* Drug: doxorubicin hydrochloride
* Drug: gemcitabine hydrochloride
* Drug: ifosfamide
* Drug: paclitaxel


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed transitional cell carcinoma of the urothelium Measurable disease, defined as unresectable or metastatic urothelial tract tumors OR Evaluable disease, defined as T3b or T4a bladder tumors PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70-100% Life expectancy: Not specified Hematopoietic: Granulocyte count greater than 1,500/mm^3 Platelet count greater than 150,000/mm^3 Hepatic: Bilirubin less than 1.5 times normal SGOT less than 2 times normal Renal: Creatinine less than 1.5 mg/dL OR Creatinine clearance greater than 60 mL/min Cardiovascular: No New York Heart Association class III or IV heart disease No serious cardiac arrhythmias, including first, second, or third degree heart block LVEF at least 50% Other: No uncontrolled infection No other active malignancy except curatively treated nonmelanomatous skin cancer or carcinoma in situ of the cervix Fertile patients must use effective barrier contraception before, during, and for 6 months after study and are encouraged to continue for 2 years or longer after study PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior systemic chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 3 weeks since prior radiotherapy Surgery: See Disease Characteristics

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: filgrastim|nan|
|Drug: cisplatin|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: gemcitabine hydrochloride|nan|
|Drug: ifosfamide|nan|
|Drug: paclitaxel|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage III bladder cancer, recurrent bladder cancer, stage IV bladder cancer, transitional cell carcinoma of the bladder, metastatic transitional cell cancer of the renal pelvis and ureter, regional transitional cell cancer of the renal pelvis and ureter, recurrent transitional cell cancer of the renal pelvis and ureter