Nab-Paclitaxel to Paclitaxel in Advanced Urothelial Cancer Progressing on or After Platinum Containing Regimen.
Condition: Urothelial Cancer
Intervention: Nab-Paclitaxel; Paclitaxel
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 199.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to compare the effects on urothelial cancer of nab-paclitaxel
      compared to paclitaxel to treat this disease.

      This research is being done because currently there is no effective treatment for urothelial
      cancer that has progressed after prior chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed diagnosis of TCC of the urinary tract
             (bladder, urethra, ureter, renal pelvis) and metastatic or locally advanced inoperable
             disease extent (T4, N2, N3 or M1 disease)

        Note: Mixed histologies (except small cell) permitted if predominately TCC by IHC.

          -  Patients must have evidence of metastatic disease, but measurable disease is not
             mandatory. To be considered evaluable for the overall response rate (complete and
             partial response), patients must have at least one measurable lesion as follows:

               -  X-ray, physical exam ≥ 20 mm

               -  Conventional CT scan, MRI ≥ 20 mm

               -  Spiral CT scan ≥ 10 mm

          -  Male or female, 18 years of age or older.

          -  ECOG performance status ≤ 2 at study entry

          -  Adequate hematological, renal and hepatic functions as defined by the following
             required laboratory values obtained within 14 days prior to randomization. If anemic,
             patients should be asymptomatic and should not be decompensated.

               -  Absolute neutrophil count (ANC) ≥ 1.5 x10^9/L (1,500 cells/mm3)

               -  Platelet count ≥ 90 x10^9/L (100,000/mm3)

               -  Hemoglobin ≥ 90 g/L

               -  Calculated creatinine clearance > 25 mL/min (Cockcroft and Gault formula)

               -  Total bilirubin ≤ 1.5 times the upper limit of normal (≤ 2.5X if Gilbert's
                  disease)

               -  ALT (SGPT) ≤ 3 x ULN or ≤ 5 x ULN if hepatic metastases are present

          -  Patients may have had prior neoadjuvant or adjuvant therapy for completely resected
             disease, provided it was completed at least 12 months prior to randomization. Patients
             must have recovered from any acute toxic effects to ≤ Grade 2 from any prior
             treatments. Neoadjuvant or adjuvant chemotherapy will be considered to have been first
             line therapy in the metastatic setting if the patient progressed within 12 months of
             the last dose.

          -  Patients must have received one and only one prior chemotherapeutic regimen which
             included a platinum (at least one cycle) for metastatic/recurrent disease. Treatment
             must have been discontinued at least 4 weeks prior to randomization in this study.
             Patients must have recovered from any acute toxic effects to ≤ Grade 2 from any prior
             treatments

          -  Patients may not have had any prior therapy with a taxane in any setting.

          -  Patients may have had prior investigational agents but these must have been
             discontinued at least 4 weeks prior to randomization. Patients must have recovered
             from any acute toxic effects to ≤ Grade 2 from any prior treatments.

          -  Prior treatments with radiation therapy in the adjuvant and/or metastatic setting are
             permitted provided that at least 2 weeks have elapsed since the last fraction of
             radiation therapy and all treatment related adverse events are ≤ Grade 1 at the time
             of randomization.

          -  Patients may have had prior surgery provided that at least 4 weeks elapsed between the
             end of surgery and randomization onto the study. Patients must have recovered from any
             acute toxic effects to ≤ Grade 2 from any prior treatments.

          -  Patients may have peripheral neuropathy from previous treatments providing that it is
             ≤ Grade 1.

          -  Patient is able (i.e. sufficiently fluent) and willing to complete the health and
             demographic, quality of life, and health utilities questionnaires in either English or
             French. The baseline assessment must be completed within required timelines, prior to
             registration/randomization. Inability (illiteracy in English or French, loss of sight,
             or other equivalent reason) to complete the questionnaires will not make the patient
             ineligible for the study. However, ability but unwillingness to complete the
             questionnaires will make the patient ineligible.

          -  Patient consent must be appropriately obtained in accordance with applicable local and
             regulatory requirements. Each patient must sign a consent form prior to enrollment in
             the trial to document their willingness to participate.

          -  Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
             test within 7 days prior to randomization. In addition to routine contraceptive
             methods, "effective contraception" also includes heterosexual celibacy and surgery
             intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined
             as a hysterectomy, bilateral oophorectomy, bilateral tubal ligation or
             vasectomy/vasectomized partner. However, if at any point a previously celibate patient
             chooses to become heterosexually active during the time period for use of
             contraceptive measures outlined in the protocol, he/she is responsible for beginning
             contraceptive measures.

          -  Patients must be accessible for treatment and follow up. Patients registered on this
             trial must be treated and followed at the participating centre. This implies there
             must be reasonable geographical limits (for example: 1 ½ hour's driving distance)
             placed on patients being considered for this trial. Investigators must assure
             themselves the patients registered on this trial will be available for complete
             documentation of the treatment, adverse events, response assessment and follow-up.

          -  In accordance with CCTG policy, protocol treatment is to begin within 5 working days
             of patient randomization.

        Exclusion Criteria:

          -  A candidate for potentially curative surgery or radiotherapy.

          -  Patients with brain metastases are ineligible if they meet at least one of the
             following criteria:

               1. diagnosis within 3 months from randomization

               2. untreated brain metastases

               3. unstable brain metastasis as defined by:

                    -  cavitation or hemorrhage in the brain lesion

                    -  symptomatic state

                    -  daily prednisone or equivalent use greater than 10 mg

        Patients do not need CT/MRI scans to rule out brain metastases unless there is a clinical
        suspicion of CNS metastases.

          -  Patients with serious illness or medical condition which would not permit the patient
             to be managed according to the protocol including, but not limited to:

               1. . any evidence of severe or uncontrolled systemic disease (i.e. known cases of
                  hepatitis B or C or human immunodeficiency virus (HIV)).

               2. patients with active or uncontrolled infections.

                  Screening for chronic conditions is not required, although patients known to have
                  such conditions at screening should not be included.

          -  Women who are pregnant or breastfeeding.

          -  Patients with history of allergic or hypersensitivity reactions to any study drug or
             their excipients or with a history of allergic reactions attributed to compounds with
             similar chemical composition to any of the study drugs.

          -  Planned concomitant participation in another clinical trial of an experimental agent,
             vaccine or device. Concomitant participation in observational studies is acceptable.

          -  Patients with a history of other malignancies, except: adequately treated non-melanoma
             skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours
             curatively treated with no evidence of disease for ≥ 5 years. Prior prostate cancer is
             allowed provided that it is an incidental finding at cystoprostatectomy with a PSA
             <0.5 ng/mL at randomization or a prior diagnosis of low risk prostate cancer at any
             time as defined by ≤T2, a Gleason Score of 6 or less and PSA <10 ng/mL.