Trial of Paclitaxel Plus Gemcitabine and Cisplatin in Bladder Cancer
Condition: Urinary Bladder Neoplasms
MeSH terms: Urinary Bladder Neoplasms
Intervention: Gemcitabine; Paclitaxel; Cisplatin
Intervention description: 1000 mg/m2 will be administered as an IV infusion over 10 mg/minute on Days 1 and 8 of each cycle (each cycle is 21 days).; 175 mg/m2 will be administered as an IVPB over 3 hours on Day 2 of each cycle (each cycle is 21 days).; 70 mg/m2 will be administered as an IVPB over 2 hours on Day 2 of each cycle (each cycle is 21 days).
Intervention MeSH terms: Paclitaxel; Gemcitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Urothelial Cancer; Bladder Cancer; Metastatic

Summary:

      This trial is for people with bladder cancer that has spread. The purpose of this research
      study is to see if the chemotherapy combination of gemcitabine and cisplatin plus paclitaxel
      is safe and effective treatment for bladder cancer.

      Paclitaxel, gemcitabine and cisplatin have all been approved by the United States Food and
      Drug Administration (FDA). Gemcitabine and cisplatin is a standard treatment for bladder
      cancer. There have been studies that show that paclitaxel and cisplatin have antitumor
      activity in bladder cancer. European researchers studied paclitaxel, gemcitabine and
      cisplatin (same drug combination in this trial) and found that the combination provided good
      disease control and was well tolerated. Investigators are studying the same drug combination,
      but at different dosages and schedule.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All patients must have histologic demonstration of metastatic or locally unresectable
             transitional cell carcinoma of the urothelium. Minor components (<50% overall) of
             variants such as glandular or squamous differentiation, or evolution to more
             aggressive phenotypes, such as sarcomatoid, or small cell changes are acceptable.
             However, when these atypical histologies are dominant, other treatment approaches may
             be more appropriate, and such patients are not eligible.

          -  All patients must have measurable or evaluable disease. In general, liver and lung
             lesions should be at least 1 cm, and patients with node-only disease should have
             lesions of ≥ 1.5 cm in the largest dimension. Patients with disease confined to bone
             may be eligible if a measurable lytic defect is present. Patients with a 3-dimensional
             mass or pelvic sidewall fixation on bladder examination under anesthesia are
             considered to have measurable disease.

          -  All patients must have adequate physiologic reserves as evidenced by:

          -  Life expectancy of at least 12 weeks.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.

          -  No clinical history of heart disease and a normal EKG or an ejection fraction measured
             by echocardiogram or MUGA scan of at least 45%.

          -  Transaminase less than twice the upper limit of normal. Bilirubin <1.5 mg%.

          -  Serum creatinine ≤2.0 mg/dL. Patients presenting with obstructive uropathy may be
             eligible if they show excellent response to nephrostomy drainage.

          -  Absolute neutrophil count ≥1500; platelet count ≥100,000.

          -  Patients must not have had any previous systemic chemotherapy for bladder cancer,
             including neoadjuvant or adjuvant treatment given remotely. Gemcitabine/cisplatin is
             the standard of care for metastatic urothelial cancer. Patients who have received
             treatment would be either resistant or refractory to additional doses. In addition,
             they would have residual adverse effects from treatment and would be particularly
             susceptible to further neuropathic adverse events. Any prior intravesicular therapy is
             allowed.

          -  Women of childbearing potential must have a negative pregnancy test prior to starting
             therapy. Men and women of childbearing potential must be willing to consent using
             effective contraceptive while on treatment and for a reasonable period thereafter.

          -  Patients must not have an active, or likely to become active, second malignancy.

          -  Patients must be at least 6 weeks out from pelvic irradiation, and must not have had
             more than 10% of the bone marrow irradiated.

        Exclusion Criteria:

          -  Patients with uncontrolled CNS metastasis are not eligible.

          -  Patients with a history of peripheral neuropathy greater than grade 1 are not
             eligible.

          -  Pregnant women are excluded.