Neoadjuvant Cisplatin, Gemcitabine, Sunitinib Malate + Radical Cystectomy for TCC
Condition: Transitional Cell Carcinoma of the Bladder
MeSH terms: Carcinoma; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms
Intervention: Gemcitabine; Cisplatin; Sunitinib Malate; Radical Cystectomy
Intervention description: Gemcitabine ( 1000 mg/m2) IV days 1 and 8; Cisplatin (70 mg/m2) IV day 1; Sunitinib malate (37.5 mg) oral daily for days 1-14; Radical cystectomy performed no sooner than 2 weeks but within 6 weeks of the last dose of sunitinib malate.
Intervention MeSH terms: Gemcitabine; 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: TCC

Summary:

      This trial will investigate the activity of sunitinib combined with cisplatin and gemcitabine
      followed by radical cystectomy in patients with Transitional Cell Carcinoma (TCC) of the
      Bladder.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histological proof of muscle-invasive transitional cell carcinoma of the bladder
             (stage II-III) with no evidence of metastatic disease (focal squamous and/or
             adenocarcinoma differentiation allowed, sarcomatoid and small-cell components not
             allowed). Patient with any degree of fixation of the pelvic sidewall are not eligible.

          -  Must be willing to undergo a cystoscopy if tumor block is not available prior to
             registration for protocol therapy.

          -  Eligible for radical cystectomy as per the attending urologist.

          -  Prior radiation therapy to bone marrow is allowed to < 25% of the marrow, and must be
             completed at least 6 months prior to registration for protocol therapy

          -  Written informed consent and HIPAA authorization for release of personal health
             information.

          -  Age > 18 years at the time of consent.

          -  Females of childbearing potential and males must be willing to use an effective method
             of contraception (hormonal or barrier method of birth control; abstinence) from the
             time consent is signed until 6 weeks after treatment discontinuation.

          -  Females of childbearing potential must have a negative pregnancy test within 7 days
             prior to being registered for protocol therapy.

        Exclusion Criteria:

          -  No prior radiotherapy to the pelvis.

          -  No prior malignancy is allowed except for adequately treated basal cell or squamous
             cell skin cancer, in situ cervical cancer, Gleason< grade 7 prostate cancers, or other
             cancer for which the patient has been disease-free for at least 5 years.

          -  No treatment with any investigational agent within 30 days prior to registration for
             protocol therapy.

          -  No cerebrovascular accident or transient ischemic attack within 6 months prior to
             registration for protocol therapy.

          -  No evidence of pulmonary embolism within 6 months prior to registration for protocol
             therapy.

          -  No uncontrolled hypertension (>150/100 mm Hg despite optimal medical therapy).

          -  No evidence of ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade 2.

          -  No history of uncontrolled/untreated thyroid dysfunction.

          -  No prolonged QTc interval (> 450 msec) on pre-entry electrocardiogram obtained within
             28 days prior to being registered on study.

          -  Patients on warfarin (>2mg) for thrombosis must be able and willing to switch to low
             molecular weight heparin prior to registration for protocol therapy.

          -  No use of drugs having proarrhythmic potential (terfenadine, quinidine, procainamide,
             disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide and
             flecainide) within 7 days prior to registration for protocol therapy.

          -  No use of CYP3A4 inhibitors (see section 5.3 for a list) within 7 days of registration
             for protocol therapy.

          -  No use of CYP3A4 inducers (see section 5.3 for a list) within 14 days of registration
             for protocol therapy.

          -  No use of amiodarone (CYP3A4 inhibitor) within 6 months of registration for protocol
             therapy.

          -  Females must not be breastfeeding.