OBJECTIVES:

• Determine the response rate in patients with previously treated, locally advanced or metastatic transitional cell carcinoma of the urothelium treated with trastuzumab (Herceptin).
• Determine the safety of this drug in this patient population.
• Determine overall and progression-free survival of this patient population treated with this drug.

OUTLINE: Patients receive a loading dose of trastuzumab (Herceptin) IV over 90 minutes on day 1 of week 1. For all subsequent doses, patients receive trastuzumab IV over 30 minutes weekly. Treatment may continue for more than 1 year in the absence of unacceptable toxicity or disease progression.

Patients are followed every 3 months for 1 year and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 13-40 patients will be accrued for this study within 13-18 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed transitional cell carcinoma (TCC) of the urothelium, including the bladder, urethra, ureter, or renal pelvis

  • No pure adenocarcinomas, pure squamous cell carcinomas, small cell carcinoma, or only small foci of TCC (less than 10% of tumor specimen)
  • Locally advanced (T4b) TCC of the bladder OR
  • Metastatic (N2 or N3 or M1) TCC of the urothelium
  • HER2 expression (3+) as determined by immunohistochemistry or gene amplification by fluorescent in situ hybridization
• Must not be a candidate for potentially curative surgery or radiotherapy

• Measurable disease

  • At least 1 unidimensionally measurable lesion of at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

  • The following lesions are considered nonmeasurable:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Lymphangitis cutis/pulmonis
    • Abdominal masses not confirmed and followed by imaging techniques
    • Cystic lesions
    • Primary bladder masses

• Relapsed from or failed to achieve a complete or partial response after 1 prior systemic chemotherapy regimen for TCC, including cisplatin, carboplatin, paclitaxel, docetaxel, or gemcitabine

  • Prior adjuvant or neoadjuvant chemotherapy is considered 1 prior chemotherapy regimen
  • Prior single-agent chemotherapy as a radiosensitizer is not considered a prior systemic chemotherapy regimen
• No known brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• CTC 0-2

Life expectancy:

• More than 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 75,000/mm^3

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST no greater than 2 times ULN

Renal:

• Creatinine clearance at least 30 mL/min

Cardiovascular:

• Ejection fraction at least 50% (or lower limit of normal) by echocardiogram or MUGA
• No history of ongoing congestive heart failure
• No active cardiac ischemia

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• HIV negative
• No known autoimmune disease

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior trastuzumab (Herceptin)

Chemotherapy:

• See Disease Characteristics
• At least 30 days since prior chemotherapy
• Prior doxorubicin allowed provided cumulative dose is no greater than 300 mg/m^2
• Prior epirubicin allowed provided cumulative dose is no greater than 600 mg/m^2
• No concurrent chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy except:

  • Steroids given for adrenal failure
  • Hormones administered for nondisease-related conditions (e.g., insulin for diabetes)
  • Intermittent dexamethasone as an antiemetic or for sensitivity reactions to study drug

Radiotherapy:

• See Disease Characteristics
• Prior radiotherapy allowed provided treated area is not only site of measurable disease
• At least 14 days since prior radiotherapy
• No concurrent palliative radiotherapy

Surgery:

• See Disease Characteristics
• At least 14 days since prior surgery