Erlotinib Before and After Surgery in Treating Patients With Muscle-Invasive Bladder Cancer

Phase 2

Completed

Conditions: Bladder Cancer

Interventions: Drug: Erlotinib
Procedure: Radical Cystectomy

Registration Number: NCT00380029

Lead Sponsor: UNC Lineberger Comprehensive Cancer Center

Brief Summary: RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving erlotinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving erlotinib after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well erlotinib works when given before and after surgery in treating patients with muscle-invasive bladder cancer.

Detailed Description: OBJECTIVES:

Primary

* Determine the effect of neoadjuvant erlotinib hydrochloride on histopathological, molecular, and genetic correlates in patients undergoing radical cystectomy for muscle-invasive bladder cancer.

Secondary

* 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 pathologic stage T3 (pT3), Node positive (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 the epidermal growth factor receptor (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 disease.

Patients are followed periodically for up to 5 years after surgery.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 27

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Erlotinib	Radical Cystectomy	erlotinib given before and after transurethral resection of a bladder tumor, TURBT
Erlotinib	Erlotinib	erlotinib given before and after transurethral resection of a bladder tumor, TURBT

Primary Outcome Measures

Name	Time	Method
EGFR Activation Signal (AKT2) Expression to Predict Sensitivity to Erlotinib	4 weeks before treatment and 4 weeks post treatment	Determine the effect of neoadjuvant erlotinib hydrochloride on histopathological, molecular, and genetic correlates in patients undergoing radical cystectomy for muscle-invasive bladder cancer. Gene expression of pre-treatment and post-treatment tumor samples were analyzed to define molecular determinants of response or resistance to epidermal growth factor receptor (EGFR) inhibition. Both in vitro and in vivo EGFR-associated signatures were evaluated on pre-treatment bladder tumors. Candidate molecular determinants of sensitivity to EGFR inhibition were characterized and examined for their ability to predict sensitivity to EGFR inhibitors in vitro.

Secondary Outcome Measures

Name	Time	Method
Pathological Complete Response Rate	4 weeks	Determine the pathological complete response rate (P0 rate) after undergoing radical cystectomy (RC). Evaluated using Response Evaluation Criteria In Solid Tumors (RECIST). Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Number of Subjects Experiencing Adverse Events	4 weeks - 2 years following surgery	The incidence of all toxicities observed during neoadjuvant and adjuvant treatment phase.Toxicity will be graded per the Common Terminology Criteria for Adverse Events (CTCAE) 2.0.
Disease Recurrence and Progression Rates After Cystectomy	2 years	To determine disease recurrence/progression rates after cystectomy in patients treated with erlotinib
Overall Survival Rate	25 months	The number of patients who remained alive and with no evidence of disease at the mean (range) follow-up of 24.8 months (3.0-36.6).