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A Single Arm, Multicenter, Open-label Phase II Trial of Cabazitaxel as Second Line Treatment of Patients With Locally Advanced or Metastatic Urothelial Carcinoma

Phase 2
18 Years
Open (Enrolling)
Urothelial Carcinoma

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Trial Information

A Single Arm, Multicenter, Open-label Phase II Trial of Cabazitaxel as Second Line Treatment of Patients With Locally Advanced or Metastatic Urothelial Carcinoma

For those patients with advanced bladder cancer who have progressed on a platinum based
regimen, no widely accepted standard second line therapy currently exists. Taxanes including
paclitaxel and docetaxel have exhibited limited clinical activity in this disease and are
sometimes given off study. Cabazitaxel is a novel semi-synthetic taxane with a low affinity
for the multidrug resistance 1 protein. In cell lines cabazitaxel is as potent as docetaxel,
but in tumor cells that are resistant to taxanes, cabazitaxel overcome taxanes resistance.

In recent clinical data, this drug was shown to have potent activity in patients with
metastatic prostate cancer resistant to docetaxel. Based on this phase III data, cabazitaxel
was recently approved in the US, Europe and in Israel for these patients. The main toxicity
of this taxane is neutropenia and diarrhea, thus primary prevention with GCSF may reduce the
main toxicity of this agent.

In this phase II multicenter study, the investigators aim to evaluate the efficacy and
tolerability of this novel taxane -cabazitaxel as single agent second-line chemotherapy for
metastatic urothelial carcinoma after failure of prior platinum-based chemotherapy.

The patients are planned to receive cabazitaxel at a starting dose of 25 mg/m(2)
intravenously over 1 h, following premedication as accepted with cabazitaxel. Treatment
cycles are every 3 weeks. All patients will receive primary GCSF support.

Inclusion Criteria:

- Ages eligible for this study are 18 years and older.

- Histological or cytological diagnosis of urothelial carcinoma. Mixed histologies are
permitted as long as transitional cell carcinoma is the major component (i.e. > 50%
of the pathologic specimen). Pure or predominant squamous cell carcinomas are not

- Patients with transitional cell carcinomas of the renal pelvis and ureter are

- Patients must have metastatic or locally advanced unresectable disease.

- Patients must have received one and only one prior chemotherapeutic regimen which
included platinum (at least one cycle) for metastatic/recurrent disease. Neoadjuvant
or adjuvant chemotherapy will be considered to have been first line if the patient
progressed within 12 months of the last dose.

- Patients with disease progression more than 12 months following platinum based
chemotherapy can be included (rather than platinum re-challenge), according to the
investigator's judgment.

- ECOG performance status ≤ 2

- Estimated life expectancy of > 12 weeks.

- Patients must have measurable disease according to RECIST1.1 criteria.

- If female of childbearing potential, pregnancy test is negative within 8 days priors
to first dose of study drug.

- If fertile, patient agrees to use an effective method of contraception to avoid
pregnancy for the duration of the study.

- Adequate organ function; Absolute neutrophil count ≥1.5 x 109/L. Platelet count ≥ 100
x109/L. Hemoglobin ≥ 9 g/dL. Total bilirubin ≤1.0x upper limit of normal. AST/SGOT
and/or ALT/SGPT ≤ 2.5x upper limit of normal. Calculated creatinine clearance > 40
ml/min (creatinine clearance will be calculated according to CKD-EPI formula:

- Able to give informed consent.

Exclusion Criteria:

- Prior taxane therapy.

- Pregnant or lactating females

- Uncontrolled brain or leptomeningeal involvement (treated brain metastasis permitted
if both known lesions and medications e.g. steroids for that indication are stable).

- History of serious or concurrent illness that might be aggravated by study treatment.

- Known human immunodeficiency virus (HIV) infection or active hepatitis B/C.

- History of class II-IV congestive heart failure.

- Significant renal impairment.

- Uncontrolled hematuria.

- History of severe hypersensitivity reaction (≥grade 3) to docetaxel.

- History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing

- Concurrent or planned treatment with strong inhibitors or strong inducers of
cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are
already on these treatments) (see Appendix).

- Other malignancies except adequately controlled basal cell carcinoma of the skin or
carcinoma in situ of the cervix or incidental prostate cancer (T1a, Gleason < 7 PSA <
10ng/ml) or any other tumor within 2 years prior to enrollment.

- Other investigational therapy or radiation therapy within 30 days before

- Patients not willing to employ adequate contraception for the duration of the study.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate

Outcome Description:

The primary end point is objective response rate (ORR): CR+ PR, assessed according to response evaluation criteria in solid tumors (RECIST 1.1) guidelines.

Outcome Time Frame:

May-2014 (up to 2 years)

Safety Issue:


Principal Investigator

Avivit - Pe'er, Dr.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Rambam MC


Israel: Ministry of Health

Study ID:




Start Date:

May 2012

Completion Date:

July 2015

Related Keywords:

  • Urothelial Carcinoma
  • Carcinoma
  • Carcinoma, Transitional Cell