Heart Safety Study of Ondansetron in Children Receiving Chemotherapy

Children receiving chemotherapy for cancer at the Jimmy Everest Center for Cancer and Blood
Disorders in Children also often receive an IV dose of an antiemetic for prophylaxis. The
most common antiemetics used are in the family of 5HT3 antagonists, specifically granisetron
and ondansetron. Prior to a recent recommendation by the FDA, we have used ondansetron 0.45
mg/kg IV. Based on adult ECG data, the recommended dose of ondansetron has been changed to
no greater than 0.15 mg/kg. We have prior studies showing that the bigger dose is better at
preventing nausea and vomiting. Therefore we are studying ECG data in patients receiving
ondansetron and chemotherapy. Each subject will have two identical cycles of chemotherapy.
Prior to the first of the two cycles they will be randomized to receive one of two doses of
ondansetron with the first cycle and the other dose with the second cycle. The two doses
are the recommended dose of 0.15 mg/kg and a higher dose of 0.3 mg/kg. The dose level the
patient receives each cycle will be blinded to the investigator and the subject.

Prior to the first dose of investigational ondansetron, the patient will have an ECG. This
ECG will be repeated 30 minutes after the ondansetron is administered and just before
chemotherapy administration, and repeated again 30 minutes later. The change in the QTc
intervals will be calculated by two independent pediatric cardiologists who are also blinded
to the ondansetron dose level received. This process will be repeated with the next course
of chemotherapy, with the second dose of ondansetron. Our goal is to see if there is an
appreciable difference between the two doses in the QTc interval changes they induce.

Inclusion Criteria:

- Age 6 months to 18 years

- Diagnosis of cancer and receiving 2 identical cycles of chemotherapy within 2 months
of each other

Exclusion Criteria:

- History of cardiac conduction anomalies, myocardial infarction, structural heart
abnormalities (even if repaired)

- Pregnant or of child-bearing age and unwilling to take a pregnancy test

- Potassium or calcium outside of reference range at screening

- Liver enzymes (AST/ALT) or bilirubin >/= 2 x the upper limit of normal at screening