Neoadjuvant Gemcitabine and Fractionated, Weekly Cisplatin For Muscle Invasive Bladder Cancer and Patients Not Candidates For High Dose Cisplatin
Condition: Invasive Bladder Cancer; Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Intervention: Gemcitabine and fractionated cisplatin (combination treatment)
Intervention description: 1 Cycle = 21 days. GC x 4 cycles ----> cystectomy Gemcitabine: 1000mg/m2, days 1 and 8 Cisplatin: 35mg/m2, days 1 and 8
Intervention MeSH terms: Gemcitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The standard treatment of muscle invasive bladder cancer is to administer chemotherapy for
      approximately 3 months then to have surgery to remove the bladder. Chemotherapy may reduce
      the size of the cancer in your bladder before surgery and can also help to reduce the chance
      that your bladder cancer will come back (metastasize) in other parts of your body after
      bladder surgery.

      This study will involve testing cisplatin in lower weekly doses with gemcitabine.The purpose
      of this study is to test the effects, good and bad, of low dose weekly cisplatin and
      gemcitabine.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Pathologically confirmed muscle-invasive urothelial (transitional cell) carcinoma of
             the bladder or upper genitourinary tract.

          2. Stage T2-T4a. Patients may have nodal disease but there must be no evidence of distant
             metastases and patients must be candidates for radical cystectomy as determined by
             urologic surgeon (note from/confirmation by surgeon required).

          3. No prior systemic therapy for urothelial carcinoma. Prior intravesical therapy is
             allowed.

          4. Patients are determined by their treating oncologist to not be a candidate high dose
             cisplatin (> 70mg/m2) due to medical comorbidities.

          5. Creatinine Clearance (CrCL or eCCr)) > 25 mL/min calculated using the Cockcroft-Gault
             formula

          6. Patients without serious medical risk factors involving any of the major organ systems
             such that the investigator considers it unsafe for the patient to receive the protocol
             treatment of this study with gemcitabine and weekly fractionated cisplatin.

          7. Preexisting neuropathy < grade 2.

          8. No prior invasive malignancy within the prior two years. However, prior history of
             non-muscle invasive bladder cancer and patients with an early stage malignancy that is
             not expected to require treatment in the next 2 years (such as early stage, resected
             breast cancer, or asymptomatic prostate cancer) are eligible.

          9. ECOG performance status 0 or 1.

         10. Age ≥ 18 years of age.

         11. Not pregnant and not nursing. Women of child bearing potential must have a negative
             serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG)
             within 7 days prior to beginning of treatment. Post-menopausal women (surgical
             menopause or lack of menses >12 months) do not need to have a pregnancy test, please
             document status.

         12. Required Initial Laboratory Values:

               -  Neutrophils ≥ 1,000/μl

               -  Platelet count ≥ 100,000/μl

               -  Total bilirubin ≤ 1.5 x ULN.

               -  AST (SGOT) & ALT (SGPT) ≤ 3.0 x ULN

        Exclusion Criteria:

          1. Metastatic disease.

          2. Prior hypersensitivity to platinums that in the investigators opinion would put the
             patient at risk if re-exposed

          3. Small cell cancer of the bladder or pure adenocarcinoma. Patients with mixed
             histologies such as urothelial carcinoma with sarcomatoid features, squamous
             differentiation or adenocarcinoma are allowed as long as transitional cell cancer is
             the predominant pathologic subtype.