Neoadjuvant Dose Dense Gemcitabine and Cisplatin (DD GC) In Patients With Muscle-Invasive Bladder Cancer
Condition: Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Intervention: Gemcitabine and Cisplatin (DD GC)
Intervention description: Patients will receive six cycles of GC administered every 14 days. Gemcitabine 2,500 mg/m2 will be administered intravenously on day 1 and cisplatin 35 mg/m2 will be administered intravenously on days 1 and 2 of a 14 days cycle (with Peg GCSF). A total of six cycles of therapy will be administered followed by radical cystectomy with bilateral pelvic lymph node dissection (PLND)
Intervention MeSH terms: Gemcitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CISPLATIN; GEMCITABINE; GM-CSF; radical cystectomy; 12-071

Summary:

      The purpose of this study is to find out if standard chemotherapy (gemcitabine and cisplatin)
      given on a dose-dense treatment schedule (with less time between treatments) can help shrink
      the tumor better than standard chemotherapy given on a standard treatment schedule before the
      patient undergoes surgery for bladder cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Muscle invasive urothelial carcinoma of the bladder histologically confirmed at MSKCC
             or participating site ((Urothelial carcinoma invading into the prostatic stroma with
             no histologic muscle invasion is allowed, provided the extent of disease is confirmed
             via imaging and/or EUA.)

          -  Clinical stage T2-T4a N0/X M0 disease

          -  Medically appropriate candidate for radical cystectomy, as per MSKCC or participating
             site

          -  Karnofsky Performance Status ≥ 70%

          -  Age ≥ 18 years of age

          -  Required Initial Laboratory Values:

          -  Absolute Neutrophil Count ≥ 1000 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

        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 ≥ 2 neuropathy

          -  Preexisting grade ≥ 2 hearing loss

          -  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

          -  Ongoing cardiac dysrhythmias of NCI CTCAE Version 4.0 grade ≥ 2

          -  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

          -  Pregnancy or breast-feeding. Patients must be surgically sterile, 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.