Combination Chemotherapy in Treating Patients With Transitional Cell Cancer of the Urothelium

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. It is not yet known which combination chemotherapy regimen is most effective for transitional cell cancer of the urothelium. PURPOSE: Randomized phase II/III trial to compare different combination chemotherapy regimens in treating patients who have transitional cell cancer of the urothelium.

Detailed Description
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OBJECTIVES: Compare the antitumor activity of gemcitabine and carboplatin vs methotrexate, carboplatin, and vinblastine in patients with transitional cell cancer of the urothelium who are ineligible for cisplatin-based chemotherapy. Compare the toxicity and acute and intermediate (1-2 years) side effects of these regimens in these patients. Compare the complete response rates, progression-free survival, and overall survival of patients treated with these regimens. Compare the symptoms and quality of life of patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms. Arm I: Patients receive methotrexate* IV and vinblastine IV on days 1, 15, and 22 and carboplatin IV over 1 hour on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and carboplatin IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. NOTE: * Methotrexate is omitted for patients with pleural effusion or ascites until complete resolution and for patients with a glomerular filtration rate less than 30 mL/min or creatinine greater than 2 mg/dL Patients in either arm who achieve a complete response (CR) receive 2 additional courses of chemotherapy beyond CR. Quality of life is assessed at baseline, after every 2 courses of chemotherapy, and within 6 weeks of completion of therapy. Patients are followed within 6 weeks, every 3 months for 1 year, and then every 6 months thereafter. PROJECTED ACCRUAL: A total of 156 patients (78 per treatment arm) will be accrued for the phase II portion of this study. A total of 225 patients will be accrued for the phase II + III portions of this study within 5 years.

Official Title
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Randomized Phase II/III Study Assessing Gemcitabine/Carboplatin And Methotrexate/Carboplatin/Vinblastine In Previously Untreated Patients With Advanced Urothelial Cancer Ineligible For Cisplatin Based Chemotherapy

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

Intervention / Treatment
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* Drug: carboplatin
* Drug: gemcitabine hydrochloride
* Drug: methotrexate
* Drug: vinblastine sulfate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed transitional cell cancer of the urothelium, including the renal pelvis, ureters, urinary bladder, and urethra, meeting 1 of the following criteria: Unresected positive lymph node Distant metastases (M1, stage IV) Unresectable primary bladder cancer (T3-4) Measurable disease Ineligible for cisplatin-based chemotherapy and presenting with the following: WHO performance status 2 AND/OR Glomerular filtration rate greater than 30 mL/min but less than 60 mL/min No brain metastases or other CNS lesions PATIENT CHARACTERISTICS: Age: 18 and over Performance status: See Disease Characteristics Life expectancy: Not specified Hematopoietic: WBC at least 4,000/mm^3 Platelet count at least 125,000/mm^3 Hepatic: Bilirubin no greater than 1.25 times normal AST/ALT no greater than 3 times normal (5 times normal if liver metastases are present) Renal: See Disease Characteristics Calcium normal Other: Not pregnant or nursing Fertile patients must use effective contraception during and for 6 months after study participation No psychological, familial, sociological, or geographical condition that would preclude study participation No other prior or concurrent malignancy except cured basal cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy: No prior systemic biologic therapy Chemotherapy: See Disease Characteristics No prior systemic cytotoxic therapy (including adjuvant and neoadjuvant chemotherapy) Endocrine therapy: Not specified Radiotherapy: At least 3 months since prior radiotherapy Prior radiotherapy to study lesions allowed if there is evidence of disease progression Surgery: Not specified

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
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: carboplatin|nan|
|Drug: gemcitabine hydrochloride|nan|
|Drug: methotrexate|nan|
|Drug: vinblastine sulfate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response as assessed by RECIST criteria |  |  | 
| Toxicity as assessed by CTC v2 |  |  | 

 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, anterior urethral cancer, posterior urethral cancer, urethral cancer associated with invasive bladder cancer, metastatic transitional cell cancer of the renal pelvis and ureter, regional transitional cell cancer of the renal pelvis and ureter