Effect of Cabazitaxel on the QTc Interval in Cancer Patients

Study Overview
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Brief Summary
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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)

Detailed Description
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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.

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

Conditions
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Neoplasms, Malignant

Intervention / Treatment
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* Drug: Cabazitaxel (XRP6258)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cabazitaxel<br>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)<br>* Pharmaceutical form:solution for infusion Route of administration: intravenous<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |