This randomized phase II trial studies how well erlotinib hydrochloride works in treating patients with bladder cancer undergoing surgery. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To determine if there is a difference in EGFR phosphorylation in normal appearing bladder epithelium adjacent to tumor approximately 9-18 hours post-study dose, between patients randomized to erlotinib hydrochloride (erlotinib) weekly as compared to placebo. SECONDARY OBJECTIVES: I. Assess the tolerance of high dose weekly erlotinib compared to placebo. II. Assess the expression of phosphorylated EGF receptor in tumor tissue when available. III. Assess the expression of e-cadherin and Ki67 in normal and abnormal urothelium. IV. Assess the expression of phosphorylated ERK in normal and abnormal urothelium. V. Assess limited pharmacokinetics of weekly erlotinib. VI. Assess the expression of p53 in normal and abnormal urothelium. VII. Assess the expression of let-7 in normal and abnormal urothelium. VIII. Exploratory assessment of urination symptoms in men. OUTLINE: Patients are randomized to 1 of 2 treatment groups. GROUP I: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1, 8, and 15. Patients then undergo transurethral resection of bladder tumor (TURBT) or cystectomy on day 16. GROUP II: Patients receive placebo PO QD on days 1, 8, and 15. Patients then undergo TURBT or cystectomy on day 16. After completion of study treatment, patients are followed up for 7-14 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
50
Given PO
Correlative studies
Correlative studies
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Lahey Hospital and Medical Center
Burlington, Massachusetts, United States
University of Rochester
Rochester, New York, United States
Carolina Urologic Research Center
Myrtle Beach, South Carolina, United States
EGFR Phosphorylation in Normal Appearing Bladder Epithelium Adjacent to Tumor
EGFR phosphorylation will be assessed using Immunohistochemistry (IHC), greater mean optical density is associated with greater phosphorylation. The difference between the placebo group and the erlotinib hydrochloride group will be tested as-randomized using a two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test.
Time frame: Up to 18 hours after last study drug dose (on day 28)
EGFR Phosphorylation in Neoplastic Bladder Epithelium 9-18 Hours Post-study Dose
EGFR phosphorylation will be assessed using Immunohistochemistry (IHC), greater mean optical density is associated with greater phosphorylation.
Time frame: Up to 18 hours after last study drug dose (on day 28)
Pharmacokinetic Parameters: Erlotinib in Blood
Will be summarized by treatment arm (and, if applicable, by visit) with appropriate descriptive statistics.
Time frame: Baseline, day 8, and day 16 (day of surgery)
Pharmacokinetic Parameters: OSI-420 in Blood
Will be summarized by treatment arm (and, if applicable, by visit) with appropriate descriptive statistics.
Time frame: Baseline, day 8, and day 16 (day of surgery)
Frequency of Urination Symptoms in Men Only, Graded According to International Prostate Symptom Score (I-PSS)
A well documented survey called the International Prostate Symptom Score (I-PSS) of urination symptoms which correlates with prostatic hyperplasia in men will be filled out by men at baseline and end of study. The I-PSS is an 8-item survey; 7 questions scored from 0-5 where 0 is 'none' or 'not at all' and 5 is 'five times' or 'almost always'. The sum of the scores for the first 7 questions has a total range of 0-35 where 0 is asymptomatic, 1-7 is mild symptoms, 8-19 is moderate symptoms, and 20-35 are severe symptoms. A final quality of life question is scored from 0-6 where 0 (delighted) to 6 (terrible). This question serves as a conversation starting point between the patient and physician.
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Given PO
Ancillary studies
Undergo TURBT or cystectomy
Urology San Antonio Research PA
San Antonio, Texas, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States
Time frame: Baseline up to 18 hours after last study drug dose (on day 28)
Expression of E-cadherin
E-Cadherin expression will be assessed using Immunohistochemistry (IHC), greater membrane optical density was associated with greater expression. A two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: At time of surgery (approximately day 16)
Percentage of Cells Expressing Ki67
Ki-67 expression will be assessed using Immunohistochemistry (IHC), greater positivity was associated with greater expression. A two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: At time of surgery (approximately day 16)
Difference Between Normal and Neoplastic Tissue Phosphorylated ERK
Phosphorylated ERK will be assessed using Immunohistochemistry (IHC), greater mean optical density is associated with greater expression. A two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: At time of surgery (approximately day 16)
Difference Between Normal and Neoplastic Tissue of p53
p53 expression will be assessed using Immunohistochemistry (IHC), greater nucleus optical density and positivity was associated with greater expression. A two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: At time of surgery (approximately day 16)
Difference Between Normal and Neoplastic Tissue of Let-7
A two-sample t-test with normalizing transformation if necessary or Wilcoxon rank-sum test will be used.
Time frame: At time of surgery (approximately day 16)