A Phase II Trial of Trastuzumab (Herceptin; NSC #688097, IND #6667) in Patients With Previously Treated Advanced Urothelial Tract Transitional Cell Carcinoma

Study start date: July 1, 2002

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