Sunitinib in Treating Patients With Locally Advanced Bladder Cancer

Phase 2

Completed

Conditions: Bladder Cancer

Interventions: Drug: sunitinib malate

Registration Number: NCT00526656

Lead Sponsor: Case Comprehensive Cancer Center

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 9

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
sunitinib malate	sunitinib malate	Drug

Primary Outcome Measures

Name	Time	Method
Pathologic Complete Response Rate of Sunitinib	at 6 weeks	Number of participants who at the time of cystectomy, to have no evidence of tumor grossly and microscopically on routine Hematoxylin and Eosin stain (H\&E) (pathologic complete response or P0) will be defined as responders. All cases will be defined as responders (P0) or non-responders based on the presence of residual tumor. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progression (PD): At least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum LD since the treatment started.

Secondary Outcome Measures

Name	Time	Method
Time to Progression	at 4 weeks post-surgery	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.
Evaluate Treatment to Surgical Complication and Morbidity	following surgery at 6 weeks	Determine if surgical morbidity was increased from time of last dose to time of surgery is defined as the number of subjects with increase non-ileus related morbidity due to treatment drug during the 2 week rest period.