Erlotinib Hydrochloride in Treating Participants With Muscle Invasive or Recurrent Urothelial Cancer

PRIMARY OBJECTIVES:

I. To estimate the response rate (ie: pT0 rate) of patients with urothelial cancer treated with erlotinib prior to cystectomy.

SECONDARY OBJECTIVES:

I. To estimate the 4-year disease-free survival of patients with urothelial cancer treated with erlotinib prior to cystectomy.

II. To measure epithelial-mesenchymal transition (EMT) markers (E-cadherin, HER4, PDGFR-beta, vimentin, fibronectin) in pre- and post-treatment biopsies and correlate expression patterns with the biological responses measured below.

III. To quantify target inhibition, antiproliferation (KI-67), and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL]) in biopsies obtained from patients before, during, and after therapy.

IV. Interrogate membrane (phosphorylated EGFR) and downstream receptor signaling pathways (ERKs, AKT/mTOR, GSK-3beta) to provide further insight into whether or not a given tumor displays a biological response.

V. To correlate the changes in Ki-67 expression with changes in angiogenesis and angiogenesis related gene expression utilizing fluorescent tissue staining techniques that we have developed in the laboratory (such as two-color TUNEL, phosphor-receptor, and microvessel density.) VI. To profile messenger ribonucleic acid (mRNA) expression in pre- and post-treatment biopsies using Affymetrix arrays and correlate the changes observed with EMT, growth arrest, and apoptosis.

VII. To quantify EGFR copy number and correlate with changes observed with EMT, growth arrest, and apoptosis.

OUTLINE:

Participants receive erlotinib hydrochloride orally (PO) once daily (QD) for 3-5 weeks in the absence of disease progression or unacceptable toxicity. Within 24 hours of the last dose, participants undergo cystectomy.

After completion of study treatment, participants are followed up every 6 months for 1 year, then annually for 4 years.