Treatment of Locally Advanced or Metastatic Transitional Cell Carcinoma With Cabazitaxel

Inclusion Criteria:

• Written informed consent

• Age ≥ 18

• Life expectancy ≥ 12 weeks

• Patients with histology/cytology confirmed Transitional Cell Carcinoma (TCC) includingmixed pathology with predominantly TCC, with locally advanced (T4b) or metastatic (lymph node or visceral) TCC arising from bladder or upper urinary tracts.

• Treated patients with incidental prostate cancer (pT2, Gleason ≤ 6) and PSA (ProstateSpecific Antigen) ≤ 0.5 ng/mL are eligible

• Measurable disease as per RECIST Criteria 1.1

• ECOG Performance Status 0-1.

• Previously received first line platinum based treatment.

• Recurrence within 12 months (by RECIST criteria version 1.1) from last cycle ofchemotherapy.

Exclusion Criteria:

• Previous therapy with a taxane.

• Pure non TCC histologies

• Grade II or more peripheral neuropathy

• Prior surgery, radiation, chemotherapy, or other anti-cancer therapy within 4 weeksprior to enrolment in the study.

• Uncontrolled severe illness or medical condition (including uncontrolled diabetesmellitus)

• Inadequate organ and bone marrow function as evidenced by:

• Hemoglobin < 9.0 g/dL

• Absolute neutrophil count < 1.5 x 109/L,

• Platelet count < 100 x 109/L,

• AST/SGOT and/or ALT/SGPT > 2.5 x ULN;

• Total bilirubin > 1.0 x ULN,

• Serum creatinine > 1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearancewill be calculated according to CKD-EPI formula and patients with creatinineclearance ≤ 30 mL/min should be excluded (see Appendix 6 for formula)

• Symptomatic brain metastases or leptomeningeal disease (CT or MRI scan of the brainrequired only in case of clinical suspicion of central nervous system involvement).

• History of another neoplasm except non-metastatic melanoma skin cancers, carcinoma insitu of the cervix, or cancer cured by surgery, small field radiation or chemotherapy < 5 years prior to randomization.

• History of inflammatory bowel disease, significant bowel obstruction.

• History of hypersensitivity to platinum, gemcitabine, taxanes, Polysorbate-80, or tocompounds with similar chemical structures.

• Any of the following events within 6 months prior to randomization: myocardialinfarction, severe/unstable angina, coronary/peripheral artery bypass graft surgery,clinically symptomatic and uncontrolled cardiovascular disease, or clinicallysignificant arrhythmias (grade 3-4).

• Concurrent treatment with strong inhibitors of cytochrome P450 3A4 or patientsplanning to receive these treatments. For patients who were receiving treatment withsuch agents, a one-week washout period is required prior to randomization.

• Women who are breastfeeding and women of child bearing potential (not postmenopausal (12 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus))unless in agreement to use an adequate method of contraception during the treatmentperiod and for 6 months after the last dose of the study drug. Men unless in agreementthat they will use effective contraception (and condom to protect against exposure toseminal liquid) whilst participating in the trial and for 6 months after the last doseof study medication.