Cabazitaxel in Patients With Urothelial Carcinoma Who Have Disease Progression Following Platinum-Based Chemotherapy
Condition: Urothelial Carcinoma
MeSH terms: Carcinoma; Carcinoma, Transitional Cell; Disease Progression
Intervention: Cabazitaxel; Neulasta; CT Scan; Blood Draw
Intervention description: Cycle 1: 20 mg/m2 in 250cc NS via IV on Day 1 every 21 days
Following cycles: 20 mg/m2 or escalated to 25 mg/m2 or reduced by 5 mg/m2 in 250cc NS via IV on Day 1 every 21 days at investigator's discretion
Treatment continues until disease progression, intercurrent illness preventing further treatment, unacceptable adverse event(s), patient withdraws from the study, or changes in the patient's condition which render further treatment unacceptable in the judgment of the investigator; 6 mg via SQ on Day 2 (24-48 hours post-cabazitaxel) every 21 days; CT scan of chest, abdomen, and pelvis to assess disease following every 3rd cycle of treatment (approximately every 9 weeks); Approximately 2 tablespoons of blood will be taken to test complete blood count, glucose, hematology, electrolytes, liver function, creatinine clearance, and a chemistry profile. This week be done weekly during the first cycle of treatment
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Urothelial carcinoma; Urothelial cancer

Summary:

      There is no accepted standard chemotherapy approved for use in the second line for patients
      with advanced urothelial carcinoma whose cancer has progressed on combination chemotherapy
      including either cisplatin or carboplatin. The chemotherapy class called taxanes, either as
      single agents or in combination, have demonstrated modest efficacy in small studies.
      Cabazitaxel is an agent in the taxane family designed to be active in the setting of acquired
      multi-drug resistance that arises in some tumors. The objective of this study is to evaluate
      the safety and efficacy of this agent in patients with urothelial carcinoma refractory
      compared to combination platinum based chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed urothelial carcinoma

          -  Patients must have measurable disease

          -  Patients must have been previously treated with a platinum-based regimen, either in
             the neoadjuvant, adjuvant or first line setting

          -  Patients can have had disease progression while on platinum chemotherapy, or
             progression within 12 months of completion of therapy

          -  At least 4 weeks must have passed since the last dose of previous chemotherapy

          -  Age > 18 years

          -  ECOG performance status < 2 (Karnofsky > 60%)

          -  Life expectancy of greater than 6 months

          -  Patients must have adequate organ and marrow function as defined below:

          -  absolute neutrophil count > 1,500/mcL

          -  hemoglobin > 9.0 g/dl

          -  platelets > 100,000/mm3

          -  total bilirubin < normal institutional limits (ULN)

          -  AST(SGOT)/ALT(SGPT) < 1.5 X institutional upper limit of normal

          -  creatinine <1.5 x ULN OR creatinine clearance measured > 50 mL/min/1.73 m2for patients
             with creatinine levels above institutional normal or calculated clearance < 60 by 24
             hour urine

          -  Peripheral neuropathy: must be < grade 1

          -  Women of childbearing potential must have a negative pregnancy test, and patients must
             use adequate contraception during study and for 3 months thereafter

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Patients with any component of small cell carcinoma

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier

          -  Patients who are receiving any other investigational agents

          -  Patients with known brain metastases

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to taxane chemotherapy

          -  Patients with a history of severe hypersensitivity reaction to Cabazitaxel or other
             drugs formulated with polysorbate 80

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnant and breastfeeding women

          -  HIV-positive patients on combination antiretroviral therapy

          -  Patients who have previously been treated with taxane regimens for bladder cancer or
             other malignancies

          -  Patients who have had more than one platinum based chemotherapy regimen

          -  Patients whose cancer has progressed more than 12 months following abstinence from
             platinum based chemotherapy can be included on study at the discretion of the
             investigator, however should first be considered for platinum re-challenge