Urinary Tract Urothelial Carcinoma Clinical Trial
Official title:
A Phase II Study of Intravesical Bacillus Calmette-Guerin Followed by Sunitinib for the Treatment of High Risk Non-muscle Invasive Lower Urinary Tract Urothelial Carcinoma
A majority of patients with bladder cancer have disease confined to the inner lining of the bladder. Patients with high risk features (high grade tumors, tumors invading into a deeper superficial layer) are routinely treated with Bacillus Calmette Guerin (BCG) instilled in their bladder after the tumor has been removed. While up to 55% of patients respond to BCG, failure to respond may suggest a more aggressive tumor that requires more definitive therapy with complete bladder removal. BCG is believed to work by stimulating the body's own immune system to attack tumor cells. It may also work by blocking the machinery that tumors use to grow blood vessels which fuel tumor growth. A newer oral drug, sunitinib has shown to help patients with metastatic bladder cancer by blocking new blood vessel growth (VEGF inhibition). The investigators are studying the use of BCG followed by sunitinib in patients with high risk non-muscle invasive bladder cancer to evaluate the complete response (no visible evidence of tumor in the bladder) at 3 months and 6 months. The investigators will also evaluate whether there is recurrent tumor at three years.
Despite a complete response of 45-55% in patients with non-muscle invasive urothelial
carcinoma involving the lower urinary tract at 3 months, many patients suffer from multiple
recurrences and progression in up to 1/3 of patients. While radical cystectomy is an
effective local therapy for patients with high risk non-invasive disease, roughly 15% of
patients will still develop progression. More importantly, the morbidity of radical
cystectomy as described above represents a barrier to treatment in some individuals. Thus,
there is a real need to identify newer therapies that reduce morbidity and improve outcomes
in patients with non-invasive urothelial cancer. While multiple drug regimens have been the
standard for many forms of cancer including invasive bladder cancer, few reports exist on
multidrug regimens for non-invasive bladder cancer.
The fundamentally agreed upon mechanism of action of BCG intravesical therapy for superficial
bladder cancer is the generation of a non-specific immune response with the expression of
cytokines by inflammatory cells resulting in tumor death. Cytokines produced by BCG therapy
such as IFNα may block vascular endothelial growth factor (VEGF) which is expressed in
superficial and invasive bladder cancer and may provide a mechanism for disease progression.
Sunitinib is an oral tyrosine kinase inhibitor that blocks VEGF. Recent reports demonstrate
clinical response in patients with metastatic bladder cancer treated with sunitinib after
recurrence following standard chemotherapeutic regimens. The addition of sunitinib following
BCG in order to consolidate VEGF inhibition may result in superior 3 month complete response
rates. We know that patients who have a complete response to BCG at 3 months have improved
disease.
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