Gemcitabine, Paclitaxel, Doxorubicin in Metastatic or Unresectable Bladder Cancer With Decreased Kidney Function
Condition: Distal Urethral Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer
MeSH terms: Carcinoma; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Urethral Neoplasms; Kidney Neoplasms; Ureteral Neoplasms; Recurrence
Intervention: Gemcitabine hydrochloride; Paclitaxel; Doxorubicin hydrochloride; Pegfilgrastim
Intervention description: Gemcitabine 900 mg/m^2 IV over 90 minutes repeat every 14 days.; 135 mg/m^2 IV over 1 hour; Doxorubicin 40 mg/m^2 IV over 20 minutes; Subcutaneously injection on day 1.
Intervention MeSH terms: Paclitaxel; Gemcitabine; Doxorubicin; Liposomal doxorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving gemcitabine, paclitaxel, and doxorubicin
      together with pegfilgrastim works in treating patients with metastatic or unresectable
      bladder cancer or urinary tract cancer and kidney dysfunction. Drugs used in chemotherapy,
      such as gemcitabine, paclitaxel, and doxorubicin, work in different ways to stop the growth
      of tumor cells, either by killing the cells or by stopping them from dividing. Colony
      stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in
      bone marrow or peripheral blood and may help the immune system recover from the side effects
      of chemotherapy. Giving combination chemotherapy together with pegfilgrastim may kill more
      tumor cells. Chemotherapy drugs may have different effects in patients who have changes in
      their kidney function.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed transitional cell carcinoma (TCC) of the
             bladder, urethra, or upper urinary tract

          -  Mixed TCC and variant histologies (i.e., small cell, squamous cell, adenocarcinoma, or
             sarcoma) allowed if present in < 50% of the biopsy specimen

          -  Patients must sign an informed consent indicating that they are aware of the
             investigational nature of this study, in keeping with the policies of the institution.

          -  Measurable disease: may include radiographic detection of metastases in lymph nodes
             (>= 1.5 cm) or liver or lung (>= 1.0 cm) OR pelvic mass palpable on examination under
             anesthesia

          -  Creatinine clearance < 60 mL/min; no renal insufficiency that requires hemodialysis;
             no renal insufficiency that is reversible in patients with tumor confined to the
             primary site (i.e., that is potentially resectable with neoadjuvant chemotherapy)

          -  Zubrod performance status 0-2

          -  Platelet count > 100,000/mm^3

          -  Absolute granulocyte count > 1,500/mm^3

          -  Bilirubin =< 2.0 mg/dL

          -  Aminotransferases (AST and ALT) =< 2 times upper limit of normal

          -  Left ventricular ejection fraction (LVEF) > 40% OR normal electrocardiogram (EKG or
             ECG) and no history of cardiac disease

          -  All patients must be evaluated in the Department of Genitourinary Medical Oncology at
             M. D. Anderson Cancer Center or participating CCOP center prior to signing informed
             consent.

          -  No prior systemic chemotherapy including, adjuvant or neoadjuvant therapy

          -  Prior intravesicular chemotherapy allowed

        Exclusion Criteria:

          -  No brain metastases

          -  Not pregnant or nursing

          -  No severe or uncontrolled infection

          -  No New York Heart Association class III-IV congestive heart failure, unstable angina,
             or history of myocardial infarction within the past 6 months

          -  No peripheral neuropathy >= grade 2

          -  No persistently uncontrolled diabetes mellitus

          -  No chronic liver disease

          -  No HIV positivity

          -  No other malignancy except nonmelanoma skin cancer unless disease-free for the past 3
             years

          -  No overt psychosis, mental disability, or other condition that would preclude giving
             informed consent

          -  No known sickle cell disease

          -  No uncontrolled severe hypertension

          -  Renal insufficiency that requires hemodialysis or renal insufficiency that is
             reversible in patients with tumor confined to the primary site (i.e., that is
             potentially resectable with neoadjuvant chemotherapy).