Paclitaxel and Radiation Therapy With or Without Trastuzumab in Treating Patients Who Have Undergone Surgery for Bladder Cancer

PRIMARY OBJECTIVES:

I. To determine the acute toxicity (=< 90 days from protocol treatment start) from
chemoradiotherapy including paclitaxel +/- trastuzumab and irradiation in non-cystectomy
patients with or without her2/neu overexpression.

SECONDARY OBJECTIVES:

I. To determine the ability of patients with bladder cancer who are non-cystectomy candidates
to complete this treatment program.

II. To evaluate the efficacy of this treatment program in achieving a complete response of
the primary tumor.

III. To measure the 5-year disease-free and overall survival of patients with bladder cancer
treated with transurethral resection of the bladder followed by chemoradiotherapy.

IV. To estimate the value of tumor and/or serum biomarkers as predictors of initial tumor
response and recurrence-free survival.

OUTLINE: This is a non-randomized, multicenter study. Patients are assigned to 1 of 2
treatment groups according to HER2/neu status (HER2/neu 2+ or 3+ staining [group 1] vs
HER2/neu 0 or 1+ staining [group 2]).

GROUP I: Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, 15, 22, 29,
36, and 43 and trastuzumab (Herceptin®) IV over 90 minutes on day 1 and then over 30 minutes
on days 8, 15, 22, 29, 36, and 43. Patients also undergo radiotherapy once daily on days 1-5,
8-12, 15-19, 22-26, 29-33, 36-40, 43-47, and 50. Treatment continues in the absence of
disease progression or unacceptable toxicity.

GROUP II: Patients receive paclitaxel and undergo radiotherapy as in group 1.

After completion of study treatment, patients are followed at 4-5 weeks, every 3 months for 1
year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

Inclusion Criteria:

- Histologically or cytologically confirmed primary transitional cell carcinoma (TCC) of
the bladder

- Histologic evidence of muscularis propria invasion

- Meets 1 of the following stage criteria:

- Stage T2-4a; NX, N0, or N1; and M0 disease

- Clinical stage T1, grade 3/3 disease AND requires definitive local therapy

- Tumor involvement of the prostatic urethra allowed provided the following criteria are
met:

- Tumor was visibly completely resected

- No evidence of stromal invasion of the prostate

- No evidence of distant metastases by chest x-ray (or chest CT scan) within 8
weeks prior to registration

- No evidence of distant metastases by abdominal/pelvic CT scan (or MRI scan)
within 8 weeks prior to registration

- Has undergone transurethral bladder resection (as thorough as is judged safely
possible) within the past 3-8 weeks, including bimanual examination with tumor mapping

- Sufficient tumor tissue available for HER2/neu analysis

- Not a candidate for radical cystectomy

- Performance status - Zubrod 0-2

- Absolute neutrophil count >= 1,800/mm^3

- Platelet count >= 100,000/mm^3

- Hemoglobin >= 8.0 g/dL (transfusion or other intervention allowed)

- Bilirubin < 2.0 mg/dL

- Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate
transaminase (SGPT) < 2.5 times upper limit of normal

- No hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

- Creatinine =< 3.0 mg/dL

- Left ventricular ejection fraction (LVEF) >= 40% by multigated acquisition scan (MUGA)
scan or echocardiogram

- No unstable angina and/or congestive heart failure requiring hospitalization within
the past 6 months

- No transmural myocardial infarction within the past 6 months

- Not pregnant or nursing

- No nursing for 6 months after completion of study treatment (for patients receiving
trastuzumab [Herceptin®])

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 6 months after
completion of study treatment

- Able to tolerate systemic chemotherapy and pelvic radiotherapy

- No other invasive malignancy within the past 3 years except nonmelanoma skin cancer

- No history of allergic reaction to study drugs

- No history of inflammatory bowel disease

- No acute bacterial or fungal infection requiring IV antibiotics

- No AIDS

- No other severe active comorbidity

- No prior systemic chemotherapy with anthracyclines or taxanes

- No prior systemic chemotherapy for TCC

- No prior pelvic radiotherapy