Neoadjuvant ABI-007, Carboplatin and Gemcitabine in Locally Advanced Bladder Cancer
Condition: Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Intervention: ABI-007; Carboplatin; Gemcitabine; Radical Cystectomy
Intervention description: ABI-007 will be administered at a dose of 260 mg/m2 over a 30 min IV infusion on day 1 of each 21 day cycle.; Carboplatin will be administered at a dose of TARGET AUC=5 over a 15 min IV infusion of day 1 of each 21 day cycle.; Gemcitabine will be administered at a dose of 800 mg/m2 over a 30 min IV infusion on days 1 and 8 of each 21 day cycle.
Intervention MeSH terms: Carboplatin; Gemcitabine; Albumin-Bound Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Locally advanced urothelial carcinoma of the bladder

Summary:

      Study participants will have been diagnosed with bladder cancer that has invaded the muscle
      wall of the bladder. Surgery is used to remove cancer when it is in the muscle of the
      bladder. Unfortunately, approximately 50% of people may have their cancer return in another
      location. For this reason, researchers are focusing on new chemotherapy regimens to be given
      before surgery (to remove the bladder) that may decrease the likelihood of cancer spreading.

      Paclitaxel, carboplatin and gemcitabine are chemotherapy drugs known to destroy bladder
      cancer cells.

      ABI-007 (brand name Abraxane™) is a form of the chemotherapy drug called paclitaxel. Standard
      paclitaxel is formulated with ethanol and a substance called Cremophor EL (polyoxyethylated
      castor oil). However, these additives are felt to contribute to the side effects (possibly
      severe) associated with paclitaxel. ABI-007 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, and is being
      evaluated in other cancers in research studies.

      This study will evaluate the safety and efficacy of the combination of ABI-007, carboplatin
      and gemcitabine in the treatment of bladder cancer prior to surgery to remove the bladder.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically proven locally advanced (T2-4,N0,M0 or Tany,N1-3,M0) urothelial
             carcinoma of the bladder and be candidates for cystectomy following chemotherapy.
             Tumor specimens must be available for assay of molecular markers (correlative
             research).

          -  Performance status of 0, 1 or 2 by Eastern Cooperative Oncology Group (ECOG) criteria.

          -  Serum creatinine <2.0 mg/dl and/or creatinine clearance >40 ml/min.

          -  Granulocyte count > 1,500/mm3, platelet > 100,000/mm3, and hemoglobin > 9.0 g/dl.

          -  Adequate liver functions: AST and ALT < 2.5 X upper limit of normal, alkaline
             phosphatase < 2.5 X upper limit of normal, and bilirubin < 1.5 mg/dl.

          -  Pre-existing peripheral neuropathy > grade 2

          -  Recovered from any effects of surgery.

          -  Women/men of reproductive potential may not participate unless they have agreed to use
             an effective contraceptive method. Women with reproductive potential must have a
             negative pregnancy test.

        Exclusion Criteria:

          -  Prior systemic or intra-arterial chemotherapy and rior radiotherapy. (intravesical
             chemotherapy allowed.)

          -  Pre-existing peripheral neuropathy > grade 2

          -  Prior malignancy [except for adequately treated basal cell (or squamous cell) skin
             cancer, in situ cervical cancer or other cancer for which the patient has been disease
             free for 2 years]

          -  Unresolved bacterial infection requiring active treatment with antibiotics. (Treatment
             may begin at the conclusion of antibiotic therapy.)

          -  Pregnant or lactating women may not participate.