Effect of Cabazitaxel on the QTc Interval in Cancer Patients (QT-Cab)

QT-Cab: An Open-Label Study to Investigate the Effect of Cabazitaxel on the QTc Interval in Cancer Patients

Primary Objective:

• To assess the potential effect on QTcF interval (QTc Fridericia) of cabazitaxel in cancer patients

Secondary Objectives:

• To assess the effects of cabazitaxel on heart rate (HR), QT, QTcB (Bazett's correction), and QTcN (population specific correction) intervals
• To assess the clinical safety of cabazitaxel
• To assess cabazitaxel plasma concentrations at Cycle 1 at early timepoints (during infusion and up to 5h post end of infusion)

Study Overview

• Status: Completed
• Conditions: Neoplasms, Malignant
• Intervention / Treatment: Drug: Cabazitaxel (XRP6258)

Detailed Description

The main period of the study consists of a maximum of 21-day screening phase, then first 2 treatment cycles with cabazitaxel. End of main period will be Cycle 3 or 30 days after last dose if patient discontinues study after 1 or 2 treatment cycles. The duration for a patient for the main period of the study will be about 9 to 10 weeks (screening, 2 cycles).

After Cycle 2, patients will have the option to continue to receive cabazitaxel and should be followed for safety reporting until 30 days after the last dose of cabazitaxel.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Sanofi-Aventis Investigational Site Number 056002
  • Gent, Belgium, 9000
    • Sanofi-Aventis Investigational Site Number 056001
• Denmark
  • Herlev, Denmark, 2730
    • Sanofi-Aventis Investigational Site Number 208002
  • København Ø, Denmark, 2100
    • Sanofi-Aventis Investigational Site Number 208001
• Netherlands
  • Maastricht, Netherlands, 6229 HX
    • Sanofi-Aventis Investigational Site Number 528001
• Sweden
  • Lund, Sweden, 221 85
    • Sanofi-Aventis Investigational Site Number 752002
  • Uppsala, Sweden, 751 85
    • Sanofi-Aventis Investigational Site Number 752001
• United States
  • California
    • San Diego, California, United States, 92103
      • Sanofi-Aventis Investigational Site Number 840006
    • San Francisco, California, United States, 94115
      • Sanofi-Aventis Investigational Site Number 840002
  • Illinois
    • Decatur, Illinois, United States, 62526
      • Sanofi-Aventis Investigational Site Number 840005
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Sanofi-Aventis Investigational Site Number 840008
  • Kentucky
    • Paducah, Kentucky, United States, 42002
      • Sanofi-Aventis Investigational Site Number 840010
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Sanofi-Aventis Investigational Site Number 840007
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • Sanofi-Aventis Investigational Site Number 840009
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Sanofi-Aventis Investigational Site Number 840003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Histologically or cytologically confirmed solid malignancy that is metastatic or unresectable, and for which standard curative measures do not exist, and a treatment with a novel taxane agent is considered.

Exclusion criteria:

• Conditions with screening ECG repolarization difficult to interpret, or showing significant abnormalities. This includes, but is not limited to: high degree AV block, pace-maker, atrial fibrillation or flutter
• QTcF >480 msec on screening Electrocardiogram (ECG)
• Significant hypokalemia at screening (serum potassium <3.5 mMol/L)
• Significant hypomagnesemia at screening (serum magnesium <0.7 mMol/L) (Note: Patient may be enrolled after correction of these laboratory abnormalities)
• Patient receives (and cannot discontinue), or is scheduled to receive a QT-prolonging drug

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cabazitaxel; At every cycle (every 3 weeks), on Day 1, patients will receive cabazitaxel, administered by intravenous (IV) infusion over 1 hour, at 25 mg/m2. An IV premedication regimen composed of up to 4 treatments (antihistamine, corticosteroids, H2 antagonist other than cimetidine at all cycles, plus palonosetron at cycle 1) will be administered before cabazitaxel infusion.	Drug: Cabazitaxel (XRP6258); Pharmaceutical form:solution for infusion Route of administration: intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in QT interval corrected calculation by Fridericia method	Cycle 1, Day 1

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in Heart rate, QT, QTcB (QT interval corrected calculation by Bazett method) and QTcN (QT interval with a population-specific correction formulae) intervals	Cycle 1, Day 1
Other ECG parameters : PR, QRS intervals and ECG morphology	Cycle 1, Day 1
Clinical safety based on adverse events, serious adverse event, laboratory assessments according to the National Cancer Institute- Common Terminology Criteria for Adverse Events v4.0 grade scaling	up to treatment discontinuation + 30 days over a maximum study period of 20 months
Cabazitaxel plasma concentrations, Cmax and partial AUC -	Cycle 1, Day 1

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: March 12, 2010
• First Submitted That Met QC Criteria: March 12, 2010
• First Posted (Estimate): March 15, 2010

Study Record Updates

• Last Update Posted (Estimate): December 16, 2011
• Last Update Submitted That Met QC Criteria: December 15, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: TES10884; 2009-016864-35 (EudraCT Number); U1111-1116-5677 (Other Identifier: UTN)