Trastuzumab in Treating Patients With Previously Treated, Locally Advanced, or Metastatic Cancer of the Urothelium

Inclusion Criteria:

• 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
  • 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
• Performance status - CTC 0-2
• More than 12 weeks
• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 75,000/mm^3
• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST no greater than 2 times ULN
• Creatinine clearance at least 30 mL/min
• 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
• 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
• No prior trastuzumab (Herceptin)
• At least 14 days since prior radiotherapy
• 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

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