A Prospective Randomized Trial for the Comparison of Two BCG Strains (Bacille Calmette-Guerin) in the Prophylaxis of Papollary Bladder Tumors Stage Ta and T1 and Treatment of Carcinoma in Situ
OBJECTIVES: I. Compare two strains of BCG (Connaught vs Tice) in terms of efficacy (yearly
relapse rate) and tolerability in patients with Ta or T1 papillary carcinoma of the urinary
bladder or carcinoma in situ of the urinary bladder. II. Assess the role of prior exposition
to mycobacteria (vaccination/Tbc) for BCG treatment efficacy in these patients. III. Define
the role of fever occurrence as a potential indicator for BCG reactivity in these patients.
IV. Evaluate the p53 status of the resected tumors and IL-8 secretion into the urine as
predictive factors of BCG reactivity in these patients. V. Evaluate disease free interval
and disease free survival, time to progression, and overall survival in these patients. VI.
Evaluate quality of life in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
center, T stage (Ta vs T1 vs CIS), and BCG immunization status (positive, i.e., greater than
10 mm diameter vs negative-indeterminate, i.e., less than 10 mm diameter). All patients
undergo complete transurethral resection (TURB) to remove bladder tumors. A Mantoux test is
performed. Patients with stage T1 disease undergo a second resection within 2-4 weeks after
initial TURB. Patients are randomized to receive either BCG Onko-Tice (arm I) or BCG
Connaught (arm II). Both arms receive BCG by catheter beginning 2-14 days after the last
TURB. Patients must hold the BCG in the bladder for 2 hours. BCG is instilled once a week
for 6 weeks. Quality of life is assessed before randomization, daily during first and last
weeks of treatment, every 6 months for the first 2 years, and then annually thereafter.
Patients are followed every 6 months for the first 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A minimum of 300 patients will be accrued for this study within 6 years.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
Assess role of prior exposition to mycobacteria
George N. Thalmann, MD
University Hospital Inselspital, Berne