A Phase II Exploratory Study of Pre-Operative Treatment With Erlotinib (Tarceva) in Muscle Invasive or Recurrent Transitional Cell Carcinoma Requiring Cystectomy

Inclusion Criteria:

1. Patients must have histologic proof of urothelial cancer. This includes bladder
cancer, in addition to other tumors of the urothelial lining including renal pelvis,
ureteral, and urethral cancer. This group may include any patient requiring
cystectomy, including patients with recurrent or extensive superficial disease
(cTa-T1N0M0), CIS (carcinoma in situ), or muscle invasive disease (cT2-3aN0M0), whose
tumor could not be completely removed at transurethral resection.

2. Patients with the following high-risk features: Micropapillary features (more than
focal on pathology); Small cell carcinoma; 3-D mass on exam under anesthesia (EUA);
Lymphovascular invasion; Hydronephrosis (unless in the opinion of the treating
physician, this is not due to tumor);High grade (grade 3) tumors of the ureter, renal
pelvis, or urethra, or tumors in these areas with radiographic abnormality large
enough to recognize as an abnormal mass by CT or MRI imaging;

3. (# 2 cont'd) Direct invasion of the prostatic stroma or the vaginal wall (ie: cT4a
disease) should be offered neoadjuvant cytoreductive chemotherapy (ie:
cisplatin-based). Patients refusing or who are not considered candidates for
cytoreductive chemotherapy may be considered eligible. Dr. Siefker-Radtke will be the
final arbiter in determining eligibility for the trial.

4. Please note that the presence of variant histologic subtypes is acceptable, except in
the case for small cell variant which is traditionally treated with cytoreductive
chemotherapy. Patients with small cell who refuse recommended cytoreductive
chemotherapy may still be considered eligible.

5. Patients must have an evaluation in the department of urology, and be deemed an
acceptable surgical candidate.

6. Patients must NOT have clinical evidence of metastatic disease by either CT or MRI of
the abdomen and pelvis, and chest x-ray. In the absence of a bone scan, patients
should be free of bone pain and have an alkaline phosphatase < 1.5 x ULN of the upper
limit of normal, or a normal bone fraction of alkaline phosphatase. If these features
are present, patients should have a bone scan and this should be interpreted as
showing no evidence of metastatic disease in order to be eligible.

7. Individuals must be > 18 years of age. In general, urothelial cancer occurs in the
6th to 7th decade of life, so it is unlikely that pediatric patients will be
included.

8. Patients, 18 years and older, must either be not of child bearing potential or have a
negative pregnancy test within 2 weeks of treatment. Patients are considered not of
child bearing potential if they are surgically sterile (they have undergone a
hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are
postmenopausal.

9. Bone marrow function: absolute neutrophil count (ANC) >/= 1,000/ul; platelets >/=
75,000/microliters.

10. Renal function: creatinine creatinine clearance of > 30 ml/min as calculated by Cockroft-Gault or by 24-hour
urine collection.

11. Hepatic function: bilirubin
12. Zubrod PS
13. Patients with second malignancies are eligible provided that the expected outcome
from the second cancer is such that this will not interfere in the delivery of this
therapy, or in doing cystectomy, and provided that the expectation of survival from
any prior malignancy is reliably > 4 years.

Exclusion Criteria:

1. Acute hepatitis or known HIV.

2. Active or uncontrolled infection.

3. Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension,
unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled
congestive heart failure, and cardiomyopathy with decreased ejection fraction 40%.

4. Prior therapy specifically and directly targeting the EGFR pathway.

5. Patients with interstitial lung disease.

6. Any concurrent chemotherapy not indicated in the study protocol or any other
investigational agent(s).

7. Patients with metastatic or surgically unresectable disease are not eligible for this
study. In addition, patients who do not agree to surgery are not eligible for this
trial.

8. Patients who have received prior systemic chemotherapy or radiation therapy for
urothelial cancer are not eligible. Any prior intravesical chemotherapy is allowed.