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.

Condition	Treatment or Intervention	Phase
transitional cell carcinoma of the bladder stage IV bladder cancer	Procedure: chemotherapy  Drug: cisplatin  Drug: docetaxel  Drug: gemcitabine  Drug: methotrexate	Phase II

Further Study Details: 

OBJECTIVES: I. 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. II. Assess the toxicities of this sequential regimen in this patient population. III. 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.

PROTOCOL 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.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--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

--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

--Patient Characteristics--

Age: 18 and over

Performance status: CALGB 0-1

Life expectancy: At least 12 weeks

Hematopoietic:

• Granulocyte count at least 1,500/mm3
• Platelet count at least 100,000/mm3
• 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
• 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

Illinois
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States
      Oncology/Hematology Associates of Central Illinois, P.C., Peoria,  Illinois,  61602,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States
Indiana
      Fort Wayne Medical Oncology and Hematology, Inc., Fort Wayne,  Indiana,  46885-5099,  United States

Study chairs or principal investigators

Walter M. Stadler,  Study Chair,  University of Chicago Cancer Research Center   

Study ID Numbers:  CDR0000067702; UCCRC-11203; NCI-G00-1733
Record last reviewed:  May 2003
Last Updated:  October 13, 2004
Record first received:  April 6, 2000
ClinicalTrials.gov Identifier:  NCT00005086
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08