Gemcitabine, Cisplatin, and Sunitinib (GC-S) as Neoadjuvant Chemotherapy in Patients With Muscle-Invasive Bladder Cancer
Condition: Bladder Cancer; Urinary Bladder
MeSH terms: Urinary Bladder Neoplasms
Intervention: Sunitinib; Gemcitabine; cisplatin
Intervention description: Sunitinib will be administered at a dose of 25mg orally once daily for 2 consecutive weeks followed by a 1 week rest period.; Gemcitabine 1,000 mg/m^2; cisplatin 35 mg/m^2 will be administered intravenously on days 1 and 8.
Intervention MeSH terms: Gemcitabine; Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Bladder; Urinary; CISPLATIN; GEMCITABINE; SU011248 (Sunitinib Malate); 08-159

Summary:

      The purpose of this study is to find out if using the combination of standard chemotherapy
      (gemcitabine and cisplatin) plus this new targeted pill (sunitinib) can help shrink your
      tumor before you undergo surgery for your bladder cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed muscle invasive transitional cell carcinoma of the bladder at
             MSKCC.

          -  Clinical stage T2-T4a N0/X M0 disease.

          -  Medically appropriate candidate for radical cystectomy as per MSKCC attending urologic
             oncologist.

          -  Karnofsky Performance Status ≥ 70%.

          -  Age ≥ 18 years of age.

          -  Required Initial Laboratory Values:

               -  Absolute neutrophil count ≥ 1500 cells/mm3

               -  Platelets ≥ 100,000 cells/mm3

               -  Hemoglobin ≥ 9.0g/dL

               -  Bilirubin ≤ 1.5 the upper limit of normal (ULN) for the institution

               -  Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for the
                  institution

               -  Alkaline phosphatase ≤ 2.5 x ULN for the institution

               -  Serum creatinine ≤ 1.5 mg/dL

          -  Estimated glomerular filtration rate ≥ 60 ml/min/1.73m2 using the CKD-EPI equation:

          -  eGFR = 141 x min(Scr/k, 1)a x max(Scr/k, 1)-1.209 x 0.993Age

          -  x 1.018 [if female] x 1.159 [if black]

          -  Scr is serum creatinine, k is 0.7 for females and 0.9 for males, a is -0.329 for
             females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max
             indicates the maximum of Scr/k or 1.

          -  If female of childbearing potential, pregnancy test is negative.

          -  Patients with reproductive potential must use an effective method to avoid pregnancy
             for the duration of the trial.

        Exclusion Criteria:

          -  Prior systemic chemotherapy (prior intravesical therapy is allowed)

          -  Prior radiation therapy to the bladder

          -  Evidence of NYHA functional class III or IV heart disease.

          -  Serious intercurrent medical or psychiatric illness, including serious active
             infection.

          -  Preexisting sensory grade 3 neuropathy

          -  Major surgery or radiation therapy < 4 weeks of starting study treatment.

          -  Concomitant use of any other investigational drugs

          -  Any of the following within the 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, or pulmonary embolism.

          -  Ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade ≥ 2.

          -  Prolonged QTc interval on baseline EKG (>450 msec for males and >470 msec for
             females).

          -  Uncontrolled hypertension (>150/100 mmHg despite optimal medical therapy).

          -  Pre-existing thyroid abnormality, with thyroid function tests that cannot be
             maintained in the normal range with medication.

          -  Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
             (AIDS)-related illness or other active infection.

          -  Concurrent treatment on another clinical trial. Supportive care trials or
             non-treatment trials, e.g. QOL, are allowed.

          -  Ongoing treatment with therapeutic doses of warfarin (low dose warfarin up to 2 mg po
             daily for thromboembolic prophylaxis is allowed).

          -  Pregnancy or breast-feeding. Patients must be surgically sterile or be
             postmenopausal,or must agree to use effective contraception during the period of
             therapy. The definition of effective contraception will be based on the judgment of
             the principal investigator or a designated associate. Male patients must be surgically
             sterile or agree to use effective contraception.