Pilot Study of Olanzapine and Aprepitant to Prevent Nausea and Vomiting in Children Receiving Chemotherapy

This will be a pilot study, designed as a randomized, crossover study comparing olanzapine
and aprepitant in pediatric oncology patients receiving highly emetogenic chemotherapy
(HEC). The primary objective is to determine the feasibility of recruitment and data
collection for conducting a larger trial aimed at comparing olanzapine and aprepitant as
antiemetic regimens and establishing efficacy of this regimens for pediatric patients
receiving HEC. Secondary objectives are to obtain preliminary data regarding the
effectiveness of olanzapine and aprepitant as well as the tolerability of olanzapine in the
pediatric oncology population.

Each patient must be planned to undergo at least 2 cycles of the same cycle of HEC. Each
patient will be randomized to receive olanzapine or aprepitant in the first cycle of
chemotherapy, and then will receive the other agent in a second cycle of chemotherapy.
Patients will also receive ondansetron and dexamethasone with each cycle. Patients with CNS
tumors will not receive dexamethasone. Response will be measured objectively recording
number of emesis and use of breakthrough medications. The medications chosen for
breakthrough medications will be at the treating physicians discretion. A complete response
will be no episodes of emesis or use of breakthrough medications. A partial response is one
or less episodes of emesis and one or less use of breakthrough medications. Nausea will be
measured based on parent and patient scales and will be a separate measure, not included in
the compete or partial response.

Inclusion Criteria:

- age greater than 4 years and less than 21 years

- patient will receive at least two cycles of the same regimen of highly emetogenic
chemotherapy

- adequate liver function - defined as total bilirubin less than or equal to 1.5 times
the upper limit of normal for age and AST/ALT less than or equal to upper limit of
normal for age

- adequate kidney function - defined as creatinine clearance or GFR greater than or
equal to 70mL/min/1.73m2 or a serum creatinine based on age/gender as follows:
Maximum serum creatinine

- 2- <6 years: Male & Female 0.8

- 6- <10 years: Male & Female 1

- 10- <13 years: Male & Female 1.2

- 13- <16 years: Male 1.5 Female 1.4

- >16 years: Male 1.7 Female 1.4

Exclusion Criteria:

- known QTc prolongation or other cardiac arrhythmia

- current treatment with another antipsychotic (for example: risperidone, quetiapine,
clozapine)

- prior adverse reaction to either olanzapine or aprepitant

- the planned two cycles of chemotherapy include ifosfamide (a patient may receive
ifosfamide as a part of his/her overall treatment plan but not during study cycles)