Primary objective: To assess the potential effect on QTcF interval (QTc Fridericia) of cabazitaxel in cancer patientsSecondary objectives:• To assess the effects of cabazitaxel on heart rate (HR), QT, QTcB (Bazett*s correction), and QTcN (population…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary end-point:
• QTcF, change from baseline, derived from core lab reading of QT interval
(baseline will be taken on Day 1 of Cycle 1, within 15 min prior to the first
cabazitaxel infusion)
Secondary outcome
Secondary end-points:
• Change from baseline in HR, QT, QTcB and QTcN intervals (same baseline as
above)
• Other ECG parameters: PR, QRS intervals, ECG morphology
• Clinical safety: adverse events and serious adverse events
• Pharmacokinetics: cabazitaxel plasma concentrations, Cmax and partial AUC
Background summary
Cabazitaxel is a new anticancer research drug that is not yet marketed in your
country. The U.S. Food and Drug Administration (FDA) has recently granted
marketing authorization for Jevtana (cabazitaxel) for the treatment of patients
with metastatic hormone-refractory prostate cancer previously treated with a
docetaxel-containing treatment regimen. To date, cabazitaxel has been
administered to more than 500 patients with various cancers, including breast
cancer.
Current regulations require that, for all potential new drugs, a specific
clinical study be conducted to assess its effects on the electrocardiogram (the
electrocardiogram or ECG measures the electrical activity of the heart). The
purpose of QT-Cab is to meet this mandatory requirement.
The QT-Cab study will therefore assess the effects of cabazitaxel on the
electrocardiogram and relate these effects with the cabazitaxel blood levels.
Study objective
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 formulae) intervals
• To assess the clinical safety of cabazitaxel
• To assess cabazitaxel plasma concentrations at Cycle 1 at early timepoints
(during 1h infusion and up to 23h post end of infusion)
Study design
This is a prospective multicenter, multinational, open-label study. Patients
enrolled must have a solid malignancy (confirmed by a cytology or pathologic
report) for which standard curative treatment does not exist and a treatment
with a novel taxane agent is considered.
The study will include 2 treatment periods (after an initial screening and
registration):
• A main period (2 cycles) which will be the basis for the study analysis:
including ECG, PK, adverse events (AEs), and serious adverse event (SAEs).
• The main period will be followed by an optional, extension period (Cycle 3
and beyond), during which patients will have the option to continue to receive
cabazitaxel treatment as long as they are benefiting from it, and provided
there is no unacceptable toxicity, or need to use anti-cancer treatment other
than cabazitaxel. During the extension period, there will be a reduced data
collection (will include SAE, related AE). During the entire treatment period,
cabazitaxel is administered every 3 weeks (preceded by an IV pre-medication
regimen). Cycle 1, Day 1 and 2 is the main visit for QT assessment:
• QTc and other ECG intervals will be assessed at Cycle 1, using a 12-lead
Holter ECG monitor. The ECG Holter recording will last 26 hours (with recording
starting before the IV pre-medication regimen, continuing through the IV
pre-medication regimen and the IV cabazitaxel infusion, and ending 23 hours
after the end of the cabazitaxel infusion).
• At Cycle 1, the IV pre-medication regimen should be administered during the
time interval ranging from 90 to 60 min before the start of cabazitaxel
infusion. Other medications could be administered on that day only if
clinically required.
• Concomitant serial PK blood sampling will also be performed on Cycle 1, Day 1
and 2. In addition, the use of concomitant medications known to significantly
prolong QT interval will be forbidden from screening until Cycle 1, Day 1 and
2. In particular, use of anti-emetics of the 5 HT-3 receptor antagonist class
(or setron class) will be strictly controlled, and restricted to palonosetron
during the last week in screening and Cycle 1, Day 1 and 2. Use of strong CYP
3A4/5 inhibitors is not authorized throughout the study (main and extension
period).
Intervention
At every cycle (every 3 weeks), on Day 1, patients will receive cabazitaxel,
administered by 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.
Study burden and risks
Risk associated with cabazitaxel:
Not all side effects of cabazitaxel are known yet. The more known significant
side effects include abnormalities in the blood (anemia, thrombocytopenia and
leucopenia). Lowering of your white blood cell count may occur, which could
increase your risk of infection. Other possible effects on your blood system
include a decrease in your red blood cells, which can lead to shortness of
breath and fatigue; and a decrease in platelets, which can lead to bleeding.
Procedure-Related Risks:
Blood drawn can cause bruising at or near the site of puncture or blood
collection. Setting up the Holter ECG with the patches can cause itching.
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Listed location countries
Age
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.
-Written informed consent
- 18 years or older
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 ECG
• Significant hypokalemia at screening (K+ <3.5 mMol/L)
• Significant hypomagnesemia at screening (Mg++ <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 (see Appendix B)
• Known allergy or intolerance to palonosetron
* Patients less than 18 years old
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-016864-35-NL |
| ClinicalTrials.gov | NCT01087021 |
| CCMO | NL32199.068.10 |