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

UNC Lineberger Comprehensive Cancer Center

Status and phase

Completed

Phase 2

Conditions

Bladder Cancer

Treatments

Drug: Erlotinib

Procedure: Radical Cystectomy

Study type

Interventional

Funder types

Other

Industry

NIH

Identifiers

NCT00380029

LCCC 0521

P30CA016086 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

27 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed muscle-invasive bladder cancer, meeting the following criteria:
- Clinical stage T2 disease
- No locally-extensive clinical stage T3 or T4 disease
- No metastatic disease (N+, M+) by physical exam or radiologic evaluation
Must have undergone prior initial or confirmatory transurethral resection of the bladder tumor (TURBT)
Candidate for and has agreed to undergo radical cystectomy with curative intent
No non-transitional cell carcinoma histologies

PATIENT CHARACTERISTICS:

Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Granulocyte count > 1,500/mm³
Platelet count > 100,000/mm³
Bilirubin normal
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 times upper limit of normal
Creatinine normal
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No contraindication to erlotinib hydrochloride or other tyrosine kinase inhibitors

PRIOR CONCURRENT THERAPY:

No prior radiotherapy or systemic chemotherapy for bladder cancer
- Prior single-dose mitomycin C allowed at the time of TURBT
Prior 6- or 12-week course of adjuvant intravesical Bacillus Calmette-Guerin (BCG) therapy with or without recombinant interferon alfa-2a allowed
At least 4 weeks since other prior or concurrent radiotherapy, chemotherapy, or hormonal therapy