Conditions: Bladder Cancer
Keywords: transitional cell carcinoma of the bladder stage II bladder cancer stage III bladder cancer stage IV bladder cancer
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 9
Healthy volunteers: no

Brief summary:
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.

Detailed description:
OBJECTIVES:

Primary

* 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.

Secondary

* 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.

Tertiary

* 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.

Arms:
arm 1: Drug

Interventions: intervention 1: sunitinib malate
Intervention descriptions: intervention 1: 50mg PO daily 4 weeks on -2 weeks off

Protocol document: