Sunitinib in Treating Patients With Locally Advanced Bladder Cancer
RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sunitinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This phase II trial is studying the side effects and how well sunitinib works in treating patients with locally advanced bladder cancer.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Single Arm, Open Label, Single Institution Study of Neoadjuvant Sunitinib (SUTENT) in Patients With Muscle-Invasive Locally Advanced Transitional Cell Carcinoma of the Bladder|
- Pathologic Complete Response Rate of Sunitinib [ Time Frame: at 6 weeks ] [ Designated as safety issue: No ]Evaluate the clinical activity of Sunitinib (Sutent®) given prior to radical cystectomy. Sunitinib will be 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks. Day 35: re-staging CT scans prior to surgery to capture any potential changes in cytology and cystoscopic examination will be performed.
- Time between treatment and surgery to avoid increased surgical complication and morbidity [ Time Frame: following surgery ] [ Designated as safety issue: Yes ]Determine if reducing the 2 week rest period that is part of the standard 4-weeks on 2-weeks off schedule of administering sunitinib (Sutent®) will provide sufficient wash-out to avoid any increased morbidity due to the possible impact of an antiangiogenic agent on wound healing and other complications.
- Time to progression [ Time Frame: at 4 weeks post-surgery ] [ Designated as safety issue: No ]Time to progression will be measured as the time from when the patient started treatment to the time the patient is first recorded as having disease progression or the date of death if the patient dies due to causes other than disease progression.
|Study Start Date:||September 2007|
|Study Completion Date:||March 2011|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
Experimental: sunitinib malate
Drug: sunitinib malate
50mg PO daily 4 weeks on -2 weeks off
Other Name: Drug
- To determine the pathologic complete response rate of sunitinib malate in patients with muscle-invasive locally advanced transitional cell carcinoma (TCC) of the bladder.
- To evaluate the safety and tolerability of sunitinib malate administered prior to radical cystectomy, including surgical outcome and surgical complications.
- To determine the clinical effects of sunitinib malate administered prior to radical cystectomy and bilateral lymph node dissection, including overall response rate using RECIST defined criteria, cytology, and histologic appearance of surgical specimen as well as time to progression.
- To assess pre-treatment tissue baseline angiogenic markers and to evaluate the magnitude of the difference among these variables with post-treatment tumor tissue after neoadjuvant sunitinib malate.
- To evaluate the effects of sunitinib malate on immunosuppressive regulatory T cells.
OUTLINE: Patients receive oral sunitinib malate once daily in weeks 1-4 (1 course). Patients undergo restaging within 1 week prior to surgery and then undergo radical cystectomy and bilateral lymph node dissection on day 42. Patients achieving a complete pathologic response at the time of surgery may receive 6 more courses of adjuvant sunitinib malate beginning 28 days after surgery at the discretion of the treating physician. Patients found to have high-risk features (i.e. pT3 or greater tumor and evidence of disease in any of the lymph nodes resected) are offered standard adjuvant systemic chemotherapy at the discretion of the treating physician.
Tumor tissue from pretreatment biopsy and radical cystectomy will be tested for VEGFR-1, VEGFR-2 and PDGF-R expression by IHC. Samples are also analyzed for quantification of cell proliferation and apoptosis and immunosuppressive regulatory T cells (T-reg) and T-reg functions.
After completion of study treatment, patients are followed at 28 days after surgery.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00526656
|United States, Ohio|
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44195|
|Principal Investigator:||Jorge A. Garcia, MD||Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|