A Phase II Study of Erlotinib (Tarceva®) in Patients With Muscle-Invasive Bladder Cancer Undergoing Radical Cystectomy
- Determine the effect of neoadjuvant erlotinib hydrochloride on histopathological,
molecular, and genetic correlates in patients undergoing radical cystectomy for
muscle-invasive bladder cancer.
- Determine the pathological complete response rate in surgical specimens from patients
treated with this drug.
- Determine recurrence and progression rates after cystectomy (up to 2 years after
surgery) in patients treated with neoadjuvant and adjuvant erlotinib hydrochloride.
- Determine 2- and 5-year disease-free, disease-specific, and overall survival rates in
patients treated with this drug.
- Determine the safety of this drug in these patients.
OUTLINE: This is an open-label study.
Patients receive oral erlotinib hydrochloride once daily for 4 weeks. Patients then undergo
radical cystectomy with curative intent. Within 12 weeks after surgery, patients resume oral
erlotinib hydrochloride* once daily for up to 2 years in the absence of disease progression
or unacceptable toxicity.
NOTE: *Patients who are candidates for adjuvant chemotherapy (e.g., found to have pT3, N+
disease) do not receive erlotinib hydrochloride after surgery.
Tumor tissue is obtained at baseline (at the original or confirmatory transurethral
resection of the bladder tumor) and at the time of cystectomy for analysis of drug-specific
and tissue-based biomarkers by western blot, immunohistochemistry, and gene array
techniques. Histopathological, molecular, and genetic correlates are analyzed to better
understand the potential effects of EGFR inhibition in transitional cell carcinoma and to
determine the effect of neoadjuvant erlotinib on gene expression. Tumor tissue is also
evaluated by real-time polymerase chain reaction to confirm drug effects on expected targets
and on EGFR expression, activity, and affected signaling pathways in the disease state and
by microarray analysis to define expression phenotypes correlating with outcome, distinguish
responders from nonresponders, and determine effects of drug treatment on gene expression in
Patients are followed periodically for up to 5 years after surgery.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Pathological Complete Response Rate
Determine the pathological complete response rate (P0 rate)on histopathological, molecular, and genetic correlates before and after therapy to better understand the potential effects of EGFR inhibition in transitional cell carcinoma
Raj S. Pruthi, MD
UNC Lineberger Comprehensive Cancer Center
United States: Food and Drug Administration
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill||Chapel Hill, North Carolina 27599-7570|