Combination Chemotherapy in Treating Patients With Advanced Bladder or Kidney Cancer

Study Overview
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Brief Summary
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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: This phase I trial is studying the side effects of giving gemcitabine, doxorubicin, and paclitaxel together with carboplatin in treating patients with advanced bladder or kidney cancer and impaired kidney function.

Detailed Description
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OBJECTIVES: Determine the safety and toxicity of dose-dense carboplatin plus paclitaxel on a weekly schedule given in sequence after gemcitabine and doxorubicin in patients with renal impairment and metastatic or locally advanced transitional cell carcinoma of the urothelium. Observe the outcome of this sequential systemic chemotherapy in these patients, or following surgical resection as adjuvant therapy in patients in whom poor renal function precludes the use of cisplatin-based chemotherapy. OUTLINE: This is a dose escalation study of carboplatin. Patients receive gemcitabine IV over 10 minutes and doxorubicin IV over 15 minutes for 5 doses on weeks 1, 3, 5, 7, and 9. Filgrastim (G-CSF) is given subcutaneously on days 3 through 10 of each 2-week course. On week 11, patients receive paclitaxel and carboplatin IV over 1 hour weekly for 12 weeks. Each cohort of 3 patients is entered on sequentially increasing doses of carboplatin. If any patient experiences dose limiting toxicity (DLT), then 6 patients are entered at that dose level. If 3 patients experience DLT at any dose level, the maximum tolerated dose has been surpassed and a total of 6 patients are treated at the previous level. Patients are evaluated at week 16 and at end of study. PROJECTED ACCRUAL: There will be 18-30 patients accrued into this study over 9-15 months.

Official Title
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Phase I Trial of Dose-Dense Gemcitabine, Doxorubicin, Then Paclitaxel Plus Carboplatin In Patients With Transitional Cell Carcinoma of the Urothelium and Impaired Renal Function

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

Intervention / Treatment
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* Biological: filgrastim
* Drug: carboplatin
* Drug: doxorubicin hydrochloride
* Drug: gemcitabine hydrochloride
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed advanced transitional cell urothelial cancer Clinical Stage IV: T any, N1-3, M0; T any, N any, M1; or cT4, Nx, M0 (bladder tumors) Pathological Stage III or IV bladder cancer: T any, N1-3, M0; T3b, N0, M0; T4, N0, M0; and T4, Nx, M0 Pathological Stage III or IV urothelial cancer of the renal pelvis or ureter: T any, N1-3, M0; T3, N0, M0; T4, N0, M0; and surgery has been performed within 10 weeks of initiation of therapy Impaired renal function (See Renal function tests) PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% OR ECOG 0-1 Life expectancy: Not specified Hematopoietic: Granulocyte count at least 1,500/mm^3 Platelet count at least 150,000/mm^3 Hepatic: Bilirubin less than 1.5 times normal Alkaline phosphatase less than 2 times normal SGOT less than 2 times normal Renal: Creatinine greater than 1.5 mg/dL but no greater than 2.5 mg/dL OR Creatinine clearance 30-59 mL/min Cardiovascular: Normal cardiac function by history, physical examination, and chest radiograph OR If prior cardiac disease, left ventricular ejection fraction must be at least 50% by radionuclide ventriculogram or echocardiogram No serious cardiac arrhythmias; including first, second, and third degree heart block No New York Heart Association class III or IV heart disease Other: No uncontrolled infection No other active cancer, except nonmelanomatous skin cancer and in situ carcinoma of the cervix curatively treated Not pregnant Effective barrier contraception required for all fertile patients during and for 6 months after therapy (encouraged to continue for 2 years or longer) PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior systemic chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to the bladder At least 4 weeks since any other prior radiotherapy Surgery: See Disease Characteristics

Ages Eligible for Study
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Minimum Age: 18 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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

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