Trial of Combination ABI-007, Carboplatin, and Gemcitabine for First Line Treatment of Advanced Urothelial Cancer
Condition: Urothelial Cancer; Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Intervention: ABI-007 (Abraxane®)
Intervention description: ABI-007 is a novel albumin-bound paclitaxel combining a protein with a chemotherapeutic agent in the particle form.
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Urothelial Cancer; ABI-007; Bladder Cancer; front-line

Summary:

      This study will evaluate the safety and efficacy of the combination of ABI-007, carboplatin
      and gemcitabine in the treatment of patients with advanced bladder cancer.

      Study participants will have been diagnosed with advanced bladder cancer. Cisplatin based
      chemotherapy in this setting has activity but is not curative. Furthermore, patients with
      this disease have comorbidities that limit the use of cisplatin based therapy. Combination
      paclitaxel, carboplatin and gemcitabine is active and well tolerated in this patient
      population.

      Paclitaxel is formulated with ethanol and a Cremophor EL (polyoxyethylated castor oil) which
      contribute to the side effects associated with paclitaxel. ABI-007 (brand name Abraxane™) is
      a form of paclitaxel that does not contain these additives and may deliver more drug to tumor
      cells. ABI-007 is approved by the United States Food and Drug Administration (FDA) in the
      treatment of metastatic (advanced) breast cancer based on superior anticancer effect, and is
      being evaluated in other cancers in research studies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female patients at least 18 years of age.

          -  Histologic or cytologic diagnosis of urothelial carcinoma (transitional cell carcinoma
             either pure or mixed histology) that is metastatic or locally recurrent or locally
             advanced and not eligible for higher priority trials.

          -  must have measurable disease.

          -  Patients must have recovered from any radiation therapy and must not have had more
             than 25% of the bone marrow irradiated.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Appendix 1.)

          -  Life expectancy of at least 12 weeks.

          -  Adequate organ and marrow function as defined below obtained within 14 days from
             registration:

               -  absolute neutrophil count >1,500/µL

               -  platelets >100,000/µL

               -  total bilirubin =1.5 mg/dL

               -  creatinine <2.0 mg/dL

               -  AST and ALT <2.5 X upper limits of normal

          -  Timing guideline for pre-study labs and measurements:

               -  All pre-study labs required for determination of eligibility are to be completed
                  within 14 days prior to registration.

               -  X-rays and/or scans to assess all disease sites are to be completed within 1
                  month prior to registration (or the next business day if falls on a weekend or
                  holiday).

          -  All patients must be informed of the investigational nature of this study and must
             sign an informed consent in accordance with institutional and federal guidelines.

        Exclusion Criteria:

          -  Previous systemic chemotherapy for the current stage of disease.

          -  Prior treatment with ABI-007 or other taxane (prior treatment with taxane in
             neoadjuvant or adjuvant setting more than one year prior to registration is allowed).

          -  Pre-existing neuropathy that is > grade 2 (i.e. interfering with patient function).

          -  History of or known spinal cord compression, or carcinomatous meningitis, or evidence
             of symptomatic brain or leptomeningeal disease on screening CT or MRI scan.

          -  Known HIV positive patients may not participate. This is to avoid additional
             complications that immune suppression and HIV infection may cause due to the intense
             nature of the chemotherapy in this trial.

          -  Concurrent treatment on another therapeutic clinical trial. Supportive care trials or
             non-treatment trials, e.g. QOL, are allowed.

          -  Pregnancy or breastfeeding. Female subjects must be surgically sterile or be
             postmenopausal, or must agree to use effective contraception during the period of
             therapy. All female subjects with reproductive potential must have a negative
             pregnancy test (serum) prior to enrollment. Male subjects must be surgically sterile
             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.

          -  Other severe acute or chronic medical or psychiatric condition or laboratory
             abnormality that may increase the risk associated with study participation or study
             drug administration, or may interfere with the interpretation of study results, and in
             the judgment of the investigator would make the subject inappropriate for entry into
             this study.