Sunitinib in Treating Patients With Locally Advanced Bladder Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00526656
Recruitment Status : Completed
First Posted : September 10, 2007
Last Update Posted : June 15, 2012
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

September 5, 2007
September 10, 2007
June 15, 2012
September 2007
March 2010   (Final data collection date for primary outcome measure)
Pathologic Complete Response Rate of Sunitinib [ Time Frame: at 6 weeks ]
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.
  • Overall response
  • Pathological complete response
  • Surgical safety
Complete list of historical versions of study NCT00526656 on Archive Site
  • Time between treatment and surgery to avoid increased surgical complication and morbidity [ Time Frame: following surgery ]
    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 ]
    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.
  • Toxicity
  • Surgical morbidity
Not Provided
Not Provided
Sunitinib in Treating Patients With Locally Advanced Bladder Cancer
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

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.



  • 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.

Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Bladder Cancer
Drug: sunitinib malate
50mg PO daily 4 weeks on -2 weeks off
Other Name: Drug
Experimental: sunitinib malate
Intervention: Drug: sunitinib malate
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
March 2011
March 2010   (Final data collection date for primary outcome measure)


Inclusion criteria:

  • Histological confirmed transitional cell carcinoma (TCC) of the bladder

    • Patients with mixed tumors (i.e., tumors containing elements of squamous cell or adenocarcinoma) are eligible
    • Patients with pure non-transitional cell carcinomas are not eligible
  • Meets 1 of the following staging criteria:

    • Tumors ≥ cT2

      • Patients with cT2 lesions must have either a bulky or fixed lesion at the time of physical examination and/or scans
    • Any cT stage with nodal-positive disease (documented by scans)

      • Patients with (+) N1-N3 disease are eligible
  • Candidate for radical cystectomy in ≥ 8 weeks while neoadjuvant sunitinib malate is administered

Exclusion criteria:

  • Any evidence of distant metastasis (excluding pelvic or retroperitoneal lymph nodes)


Inclusion criteria:

  • ECOG performance status (PS) 0-1 (Karnofsky PS greater than 70%)
  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelet count ≥ 100,000/mcL
  • Hemoglobin ≥ 8.5 g/dL
  • Total bilirubin ≤ 1.5 times institutional upper limit of normal (ULN)
  • AST and ALT ≤ 3.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN (≤ 10 times ULN in presence of bone metastasis)
  • Serum calcium ≤ 12 mg/dL
  • Creatinine ≤ 1.5 times ULN
  • INR ≤ 1.5 (except for patients receiving warfarin therapy)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study treatment
  • Disease-free of prior malignancies for ≥ 5 years except for currently treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix

Exclusion criteria:

  • NCI CTCAE grade 3 hemorrhage within 4 weeks of starting study treatment
  • Any of the following within 6 months prior to study drug administration:

    • Myocardial infarction
    • Severe/unstable angina
    • Coronary/peripheral artery bypass graft
    • Symptomatic congestive heart failure
    • Cerebrovascular accident or transient ischemic attack
    • Pulmonary embolism
  • Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥ 2, atrial fibrillation of any grade, or prolongation of the QTc interval to > 450 msec for males or > 470 msec for females
  • Hypertension that cannot be controlled by medications
  • Known HIV or AIDS-related illness
  • Infectious hepatitis type A, B, or C
  • Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results


Inclusion criteria:

  • Other systemic chemotherapy must have been completed at least 5 years prior to enrollment
  • No prior systemic chemotherapy for bladder cancer
  • No other approved or investigational anticancer treatment will be permitted during the study period, including chemotherapy, biological response modifiers, hormone therapy, surgery, palliative radiotherapy, or immunotherapy
  • No other investigational drug may be used during treatment on this protocol
  • No concurrent participation in another clinical trial

Exclusion criteria:

  • Prior intravesical chemotherapy or immunotherapy
  • Prior treatment with any other antiangiogenic therapy (including immunomodulatory agents such as thalidomide and lenalidomide and anti-VEGF therapy with agents such as bevacizumab, sunitinib malate, and sorafenib tosylate)
  • Prior surgery, radiotherapy, or systemic therapy within 4 weeks of starting the study treatment
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
P30CA043703 ( U.S. NIH Grant/Contract )
GA6180CV ( Other Grant/Funding Number: Pfizer-GA6180CV )
Not Provided
Not Provided
Case Comprehensive Cancer Center
Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Jorge A. Garcia, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Case Comprehensive Cancer Center
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP