Combination Chemotherapy in Treating Patients With Stage IV Locally Advanced or Metastatic Bladder 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: Phase II trial to study the effectiveness of combination chemotherapy in treating patients who have stage IV locally advanced or metastatic bladder cancer.

Detailed Description
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OBJECTIVES: Determine the response rate to the combination of docetaxel and methotrexate followed by gemcitabine and cisplatin in patients with stage IV locally advanced or metastatic, previously untreated, transitional cell carcinoma of the urothelium. Assess the toxicities of this sequential regimen in this patient population. Assess time to event efficacy measures including time to disease progression, duration of response, and overall survival in these patients treated with this sequential regimen. OUTLINE: Patients receive methotrexate IV on days 1 and 8 and docetaxel IV over 1 hour on day 8 every 3 weeks for 9 weeks. Patients then receive cisplatin IV over 2 hours on day 1 and gemcitabine IV over 100 minutes on days 1 and 8 every 3 weeks for 9 weeks. This 18 week sequential regimen constitutes 1 full course. Treatment continues in the absence of unacceptable toxicity or disease progression. Patients are followed until death or until 2 years after study entry, whichever comes first. PROJECTED ACCRUAL: A total of 18-46 patients will be accrued for this study within 9-24 months.

Official Title
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A Phase II Trial of Sequential Doublets Chemotherapy in Patients With Locally Advanced or Metastatic Bladder Cancer

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: docetaxel
* Drug: gemcitabine hydrochloride
* Drug: methotrexate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage IV locally advanced or metastatic transitional cell carcinoma of the urothelium that is not amenable to curative surgery or radiotherapy T4b or N2 or N3 or M1 No pure adenocarcinomas, pure squamous carcinomas, or small cell carcinoma Evaluable or bidimensionally measurable disease If only single lesion, must not be within portal of prior irradiation No active CNS metastases Adequately treated CNS metastases eligible provided stable for 8 weeks following therapy and no longer requires steroids or antiseizure medication No clinically significant pleural effusions or ascites unless drained prior to administration of methotrexate PATIENT CHARACTERISTICS: Age: 18 and over Performance status: CALGB 0-1 Life expectancy: At least 12 weeks Hematopoietic: Granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9.0 g/dL (transfusion allowed) Hepatic: Bilirubin less than 1.5 mg/dL SGOT less than 2.5 times upper limit of normal Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 50 mL/min Cardiovascular: No uncontrolled cardiac disease (e.g., congestive heart failure, arrhythmia, or angina) Pulmonary: No uncontrolled pulmonary disease (e.g., chronic obstructive pulmonary disease) Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study participation No concurrent active infection No known hypersensitivity to docetaxel, methotrexate, cisplatin, gemcitabine, filgrastim (G-CSF), oprevelkin, or any component of these products No serious concurrent medical disorder No medical or psychiatric conditions that would compromise consent or preclude completion of study No other malignancy within the past 3 years except: Carcinoma in situ of the cervix Adequately treated nonmelanoma skin cancer Stage I or II prostate cancer provided adequate local therapy (surgery or radiation) has been administered and PSA is less than 1.0 ng/mL No preexisting peripheral neuropathy grade 2 or greater PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior systemic chemotherapy for metastatic disease At least 6 months since prior neoadjuvant or adjuvant chemotherapy No other concurrent chemotherapy Endocrine therapy: No concurrent steroids Radiotherapy: See Disease Characteristics No concurrent radiotherapy Surgery: See Disease Characteristics At least 3 weeks since prior major surgery and recovered Other: No other concurrent investigational drugs

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Methotrexate will be given as a short infusion (introduced into a vein) for approximately 5 minutes on the first day (day 1). ). A week later (day 8), both methotrexate and docetaxel will be given the same way, but this will take about 1 hour. The first course of treatment consists of receiving treatment on day 1 and day 8 every 21 days for 9 weeks. X-rays or scans will then be performed to determine if your tumor is shrinking. You will then start treatment with gemcitabine and cisplatin. On the first day (day 1), you will receive both cisplatin and gemcitabine into your vein. A week later (day 8), you will receive only gemcitabine as an infusion into your vein over 100 minutes and no additional intravenous fluid will be required on that day. This second course of treatment consists of receiving treatment on day 1 and day 8 every 21 days for 9 weeks. | Drug: cisplatin<br> <br> Drug: docetaxel<br> <br> Drug: gemcitabine hydrochloride<br> <br> Drug: methotrexate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and toxic effects of giving docetaxel and methotrexate followed by gemcitabine and cisplatin |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV bladder cancer, transitional cell carcinoma of the bladder