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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

Phase 2
18 Years
Not Enrolling
Bladder Cancer

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Trial Information

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



- 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

After completion of study treatment, patients are followed at 28 days after surgery.

Inclusion Criteria


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

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

- 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

- 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

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Pathologic Complete Response Rate of Sunitinib

Outcome Description:

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.

Outcome Time Frame:

at 6 weeks

Safety Issue:


Principal Investigator

Jorge A. Garcia, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

September 2007

Completion Date:

March 2011

Related Keywords:

  • Bladder Cancer
  • transitional cell carcinoma of the bladder
  • stage II bladder cancer
  • stage III bladder cancer
  • stage IV bladder cancer
  • Urinary Bladder Neoplasms
  • Carcinoma, Transitional Cell



Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Cleveland, Ohio  44195