Cisplatin, Gemcitabine and Bevacizumab in Combination for Metastatic Transitional Cell Cancer
Condition: Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Intervention: Cisplatin; Gemcitabine; Bevacizumab
Intervention description: Cisplatin 70 mg/m2, day 1; Gemcitabine 1250 mg/m2, day 1 and 8; Bevacizumab 15mg/kg, day 1
Intervention MeSH terms: Bevacizumab; Gemcitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Cisplatin is a very important agent for the treatment of TCC as it has a single agent
      response rate of approximately 15%. However, it has been most important as a part of
      combination chemotherapy, MVAC initially and now in combination with gemcitabine. Single
      agent gemcitabine has demonstrated an overall response rate (ORR) of approximately 25%,
      including some complete responses (CR), with minimal toxicity in patients with advanced
      bladder cancer. Bevacizumab, a murine anti-human VEGF monoclonal antibody, has been advanced
      for use in combination with cytotoxic chemotherapy to delay time to disease progression in
      patients with metastatic solid tumors.

      This trial is designed to further assess the efficacy, safety and tolerability of this
      regimen in this patient population.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Previously untreated or relapsed locally advanced or metastatic transitional cell
             carcinoma of the bladder. (Patients with pathology showing ANY component of
             non-transitional cell histology are not eligible).

          -  Relapsed patients may have received prior chemotherapy ≥ one year prior to study
             registration as part of a neoadjuvant or adjuvant regimen and must not have had
             intervening therapy from the end of that treatment until study entry.

          -  Measurable disease as per RECIST.

          -  Prior radiation therapy, immunotherapy, cytokine, biologic or vaccine therapy must be
             greater than 28 days prior to being registered for protocol therapy,

        Exclusion Criteria:

          -  No known central nervous system metastasis. (imaging of brain only required if
             clinically indicated)

          -  No prior organ allograft.

          -  No history of other disease, metabolic dysfunction, physical examination finding, or
             clinical laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug or that might affect the
             interpretation of the results of the study or render the subject at high risk from
             treatment complications.

          -  No evidence of bleeding diathesis or coagulopathy.

          -  No history of serious, non-healing wound, ulcer or bone fracture

          -  No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal
             abscess within 6 months prior to being registered for protocol therapy.

          -  No prior history of malignancy in the past 5 years with the exception of basal cell
             and squamous cell carcinoma of the skin. Other cancers with low potential for
             metastasis, such as in situ cancers (e.g., Grade 1, TA TCC (low grade superficial
             bladder cancer), colonic polyp with focus of adenocarcinoma) can also be enrolled
             after approval from the study chair.

          -  No major surgical procedure, open biopsy, or significant traumatic injury less than 28
             days prior to being registered for protocol therapy.

          -  Patients are not eligible if the need for any major surgical procedure is anticipated
             during the course of the study.

          -  Any minor surgical procedures, fine needle aspirations or core biopsies must be
             greater than 7 days prior to being registered for protocol therapy except procedures
             to secure a vascular access device which must be greater than 7 days prior to the
             start of protocol therapy.