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A Trial of Cabazitaxel for Advanced Transitional Cell Carcinoma (TCC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01600339
Recruitment Status : Completed
First Posted : May 17, 2012
Last Update Posted : May 12, 2015
Sponsor:
Information provided by (Responsible Party):
Rambam Health Care Campus

Tracking Information
First Submitted Date  ICMJE February 26, 2012
First Posted Date  ICMJE May 17, 2012
Last Update Posted Date May 12, 2015
Study Start Date  ICMJE May 2012
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 10, 2015)
Response rate [ Time Frame: up to 2 years ]
The primary end point is objective response rate (ORR): CR+ PR, assessed according to response evaluation criteria in solid tumors (RECIST 1.1) guidelines.
Original Primary Outcome Measures  ICMJE
 (submitted: May 16, 2012)
Response rate [ Time Frame: May-2014 (up to 2 years) ]
The primary end point is objective response rate (ORR): CR+ PR, assessed according to response evaluation criteria in solid tumors (RECIST 1.1) guidelines.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 10, 2015)
  • Clinical benefit [ Time Frame: up to 2 years ]
    Secondary endpoints include clinical benefit with the following parameters: PR+CR+SD.
  • Duration of response [ Time Frame: up to 2 years ]
    Assessment of duration of response to treatment with Cabazitaxel.
  • Disease control rate [ Time Frame: up to 2 years ]
    Assessment of stable disease ≥ 16 weeks, PR or CR.
  • PFS [ Time Frame: up to 2 years ]
    To determine the progression free survival (PFS) of study population defined as a 20% increase in the largest diameter of the largest lesion by CT scan.
  • Overall Survival [ Time Frame: up to 2 years ]
    To determine the percentage of patients alive at data cutoff from trial entry. Overall survival will be measured from date of randomization to date of death due to any cause.
  • Safety and tolerability of treatment [ Time Frame: up to 2 years ]
    Number of participants with adverse events as a measure of safety and tolerability, assessment of dose modifications according to patient's toxicity levels.
  • Surrogate markers to cabazitaxel [ Time Frame: up to 3 years ]
    Assessment of surrogate markers to cabazitaxel response.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2012)
  • Clinical benefit [ Time Frame: May-2014 (up to 2 years) ]
    Secondary endpoints include clinical benefit with the following parmeters: PR+CR+SD.
  • Duration of response [ Time Frame: May-2014 ]
    Assessment of duration of response to treatment with Cabzitaxel.
  • Disease control rate [ Time Frame: May -2014 ]
    Assessment of stable disease ≥ 16 weeks, PR or CR.
  • PFS [ Time Frame: May-2014 ]
    To determine the progression free survival (PFS) of study population defined as a 20% increase in the largest diameter of the largest lesion by CT scan.
  • Overall Survival [ Time Frame: May-2014 ]
    To determine the percentage of patients alive at data cutoff from trial entry. Overall survival will be measured from date of randomization to date of death due to any cause.
  • Safety and tolerability of treatment [ Time Frame: May-2014 ]
    Number of participants with adverse events as a measure of safety and tolerability, assessment of dose modifications according to patient's toxicity levels.
  • Surrogate markers to cabazitaxel [ Time Frame: May -2015 ]
    Assessment of surrogate markers to cabazitaxel response.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Trial of Cabazitaxel for Advanced Transitional Cell Carcinoma (TCC)
Official Title  ICMJE A Single Arm, Multicenter, Open-label Phase II Trial of Cabazitaxel as Second Line Treatment of Patients With Locally Advanced or Metastatic Urothelial Carcinoma
Brief Summary In this phase II multicenter study, the investigators aim to evaluate the efficacy and tolerability of a novel taxane-cabazitaxel as single agent second-line chemotherapy for metastatic urothelial carcinoma.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Urothelial Carcinoma
Intervention  ICMJE Drug: CABAZITAXEL
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.
Study Arms  ICMJE Experimental: CABAZITAXEL
cabazitaxel at a starting dose of 25 mg/m
Intervention: Drug: CABAZITAXEL
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 10, 2015)
19
Original Estimated Enrollment  ICMJE
 (submitted: May 16, 2012)
48
Actual Study Completion Date  ICMJE January 2015
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 permitted.
  • Patients with transitional cell carcinomas of the renal pelvis and ureter are permitted.
  • 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: http://www.qxmd.com/calculate-online/nephrology/ckd-epi-egfr).(27)
  • 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 drugs.
  • 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 registration.
  • Patients not willing to employ adequate contraception for the duration of the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01600339
Other Study ID Numbers  ICMJE ISGUOG1101.CTIL
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Rambam Health Care Campus
Study Sponsor  ICMJE Rambam Health Care Campus
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Avivit - Pe'er, Dr. Rambam MC
PRS Account Rambam Health Care Campus
Verification Date May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP