Sunitinib in Treating Patients With Locally Advanced Bladder Cancer
Condition: Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Intervention: sunitinib malate
Intervention description: 50mg PO daily 4 weeks on -2 weeks off
Intervention MeSH terms: Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: transitional cell carcinoma of the bladder; stage II bladder cancer; stage III bladder cancer; stage IV bladder cancer

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.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

        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)

        PATIENT CHARACTERISTICS:

        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

        PRIOR CONCURRENT THERAPY:

        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