Bacillus Calmette-Guerin Followed by Sunitinib for the Treatment of High Risk Non-muscle Invasive Lower Urinary Tract Urothelial Carcinoma (Sutent)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Determine complete response rate at 3 months in patient with high risk non-invasive urothelial carcinoma of the lower urinary tract treated with a intravesical BCG followed by sunitinib [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
- Determine complete response percentage of study regimen at 6 months. [ Time Frame: 14 Weeks ] [ Designated as safety issue: Yes ]
- Assess recurrence-free survival at 2 years in patients with intact bladder. [ Time Frame: 14 weeks ] [ Designated as safety issue: Yes ]
- Determine toxicity related to treatment with BCG followed by Sunitinib. [ Time Frame: 14 weeks ] [ Designated as safety issue: Yes ]CTCAE version 3.0 will be used to characterize the toxicity
|Study Start Date:||January 2009|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Experimental: Sunitinib treatment
Intravesical BCG (81 mg Theracys BCG in 50 ml normal saline) once weekly for 6 weeks within 6 weeks of bladder biopsy confirming high risk non-muscle invasive urothelial carcinoma.
Patients are treated with a 6-week induction course of intravesical bacillus Calmette-Guerin (BCG) followed by a 2 week rest period and 4 week course of oral Sunitinib.
Patients will receive intravesical BCG (81 mg Theracys BCG in 50 ml normal saline) once weekly for 6 weeks within 6 weeks of bladder biopsy confirming high risk non-muscle invasive urothelial carcinoma. Two weeks after completion of BCG, patients will receive Sunitinib (50 mg daily) continuously for 28 days followed by a two week rest period. Patients will be reassessed with transurethral resection and urine cytology. Those with residual/recurrent disease will receive a second course identical to the initial protocol. Those with a complete response following initial or second treatment will be placed on maintenance BCG (3 week course every 6 months for 2 years). Those failing (progression, intolerance) initial/secondary treatments will be offered alternative therapy.
Other Name: Sutent
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00794950
|United States, Maryland|
|Mark P. Schoenberg, MD|
|Baltimore, Maryland, United States, 21287-2101|
|United States, Michigan|
|Alon Weizer, MD|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||Alon Weizer, MD||University of Michigan|