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