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Cabazitaxel in Platinum Pre-treated Patients With Locally Advanced or Metastatic Transitional Cell Carcinoma Who Developed Disease Progression Within 12 Months of Platinum Based Chemotherapy.

Phase 2/Phase 3
18 Years
Open (Enrolling)
Transitional Cell Carcinoma

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Trial Information

Cabazitaxel in Platinum Pre-treated Patients With Locally Advanced or Metastatic Transitional Cell Carcinoma Who Developed Disease Progression Within 12 Months of Platinum Based Chemotherapy.

Bladder cancer was the 9th most common cause of cancer worldwide in 2002. About 70% of
patients have superficial tumour and 30% have invasive tumour at diagnosis. Patients with
superficial tumour are treated by surgery, which is the only curative treatment. However,
about 50% of these patients will relapse, and cannot be cured by local treatment in the
majority of cases. The survival of untreated metastatic patients does not exceed 3 to 6
months, and systemic chemotherapy increases overall survival of patients with unresectable

However, the overall survival of patients with advanced disease treated with chemotherapy
remains short (14 months), which reflects a substantial unmet medical need for more
effective therapy in this very poor prognosis disease.

Cabazitaxel is a new taxane, taxanes have demonstrated activity in advanced bladder cancer,
and are among the most active new cytotoxic agents to be assessed in transitional cell

Cabazitaxel has demonstrated activity in cell lines with acquired resistance to doxorubicin,
vincristine, vinblastine, paclitaxel, and docetaxel.

This is a randomised, open-label, parallel-group phase 2 study of cabazitaxel versus best
supportive care (including chemotherapy).

The study is divided into three phases: screening, treatment, and follow-up. The treatment
phase comprises a maximum of six three-weekly cycles of therapy, with a post treatment
discontinuation visit taking place 3 weeks after last dose of treatment before the follow-up
phase begins.

This phase 2 study will initially recruit 25 patients and after interim analysis will to
increase to recruit 96 patients randomised between the two treatment options and the study
is expected to last about 2 years.

Inclusion Criteria:

- Written informed consent

- Age ≥ 18

- Life expectancy ≥ 12 weeks

- Patients with histology/cytology confirmed Transitional Cell Carcinoma (TCC)
including mixed 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 (Prostate
Specific 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 of

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 weeks
prior to enrolment in the study.

- Uncontrolled severe illness or medical condition (including uncontrolled diabetes

- 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
clearance will be calculated according to CKD-EPI formula and patients with
creatinine clearance ≤ 30 mL/min should be excluded (see Appendix 6 for formula)

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

- History of another neoplasm except non-metastatic melanoma skin cancers, carcinoma in
situ 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 to
compounds with similar chemical structures.

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

- Concurrent treatment with strong inhibitors of cytochrome P450 3A4 or patients
planning to receive these treatments. For patients who were receiving treatment with
such 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 treatment
period and for 6 months after the last dose of the study drug. Men unless in
agreement that they will use effective contraception (and condom to protect against
exposure to seminal liquid) whilst participating in the trial and for 6 months after
the last dose of study medication.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall response rate

Outcome Description:

To compare the overall response rate of patients administered cabazitaxel vs best supportive care (including single agent chemotherapy) in patients with transitional cell carcinoma who have previously progressed on a platinum-based regimen.

Outcome Time Frame:

Change from baseline at Week 9 and Week 18

Safety Issue:


Principal Investigator

Anjali Zarkar

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Hospitals Birmingham NHS FT


United Kingdom: National Health Service

Study ID:




Start Date:

January 2013

Completion Date:

December 2015

Related Keywords:

  • Transitional Cell Carcinoma
  • Transitional cell carcinoma
  • Bladder cancer
  • Cancer
  • Oncology
  • Cabazitaxel
  • Carcinoma
  • Carcinoma, Transitional Cell