RATIONALE: Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with combination chemotherapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining trastuzumab with combination chemotherapy in treating patients who have locally recurrent or metastatic urinary tract cancer.

OBJECTIVES:

• Determine the toxicity of the combination of trastuzumab (Herceptin), paclitaxel, carboplatin, and gemcitabine in patients with HER2-overexpressing locally recurrent or metastatic urothelial carcinoma.
• Determine the complete and partial response rates in patients treated with this regimen.
• Determine the median and overall survival of patients treated with this regimen.

OUTLINE: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15; paclitaxel IV over 3 hours and carboplatin IV over 15 minutes on day 1; and gemcitabine IV over 30 minutes on days 1 and 8. Courses repeat every 3 weeks. Patients achieving a complete response (CR) receive 3 courses past CR. Patients achieving a partial response or stable disease continue on therapy until CR or disease progression or unacceptable toxicity.

Patients are followed for disease progression and survival. Patients with HER2-negative disease are not eligible for treatment but are followed every 6 months for response and survival.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 24 months.

• Bladder Cancer
• Transitional Cell Cancer of the Renal Pelvis and Ureter
• Urethral Cancer

• Biological: trastuzumab
• Drug: carboplatin
• Drug: gemcitabine hydrochloride
• Drug: paclitaxel

DISEASE CHARACTERISTICS:

• Histologically confirmed locally recurrent or metastatic urothelial carcinoma incurable by surgery or radiotherapy

  • Transitional cell OR squamous cell

• HER2 overexpression of the primary or metastatic site evidenced by 1 of the following:

  • 2+ or 3+ staining by immunohistochemistry
  • Positive FISH defined as greater than 2 with the Vysis system or greater than 4 with the Ventana system
  • Elevated serum HER2 greater than 16 ng/mL with the OSDI assay
• Biopsy-proven HER2 overexpression of metastatic site if primary site is histologically and serologically HER2 negative*

• Bidimensionally measurable or evaluable disease

  • Disease outside previously irradiated fields NOTE: *HER2-negative patients are not eligible for treatment but are followed for response and survival

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• SWOG 0-2

Life expectancy:

• More than 12 weeks

Hematopoietic:

• Granulocyte count greater than 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No significant cardiac disease
• Ejection fraction at least 50% by MUGA or 2D echocardiogram
• No evidence of symptomatic coronary artery disease
• No active ischemia on EKG
• No history of congestive heart failure

Other:

• No active bacterial infection
• No other prior malignancy except adequately treated basal or squamous cell skin cancer or carcinoma in situ
• HIV negative
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior systemic chemotherapy for metastatic disease
• At least 6 months since prior adjuvant chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered

Surgery:

• See Disease Characteristics