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

Phase 2

Completed

Conditions: Chemotherapy Induced Nausea and Vomiting

Interventions: Drug: Olanzapine
Drug: Aprepitant

Registration Number: NCT02097823

Lead Sponsor: Indiana University

Brief Summary: The purpose of this study is to determine the feasibility of a larger trial comparing olanzapine and aprepitant and to obtain preliminary data on the effectiveness of these two medications to treat nausea and vomiting in children receiving chemotherapy. Children receiving 2 cycles of chemotherapy with a high risk of causing nausea and vomiting will receive olanzapine in one cycle and aprepitant in another cycle. Children will be randomized to see which medicine they receive first. The investigators will record the number of extra medications used for nausea, the number of times a child vomits, and the amount of nausea the child feels each day.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 15

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Olanzapine First, Aprepitant Second	Aprepitant	Will receive olanzapine (weight based dose, see below) in first cycle of chemotherapy and aprepitant (weight based dose, see below) in the second cycle of chemotherapy. All doses will be given starting 30 minutes before chemotherapy on day 1. Olanzapine dosing: \>60kg - 10mg orally daily for 4 doses 40-59.9kg - 5mg orally daily for 4 doses 20-39.9kg - 2.5mg orally daily for 4 doses \<20kg - 1.25mg orally daily for 4 doses Aprepitant dosing: \>40kg - 125mg orally on day 1, then 80mg orally daily on days 2,3 35-39.9kg - 80mg orally daily for 3 doses 20-34.9kg - 40mg orally daily for 3 doses \<20kg - 1.5-2mg/kg orally daily for 3 doses
Aprepitant First, Olanzapine Second	Aprepitant	Will receive aprepitant (weight based dose, see below) in first cycle of chemotherapy and olanzapine (weight based dose, see below) in the second cycle of chemotherapy. All doses will be given starting 30 minutes before chemotherapy on day 1. Olanzapine dosing: \>60kg - 10mg orally daily for 4 doses 40-59.9kg - 5mg orally daily for 4 doses 20-39.9kg - 2.5mg orally daily for 4 doses \<20kg - 1.25mg orally daily for 4 doses Aprepitant dosing: \>40kg - 125mg orally on day 1, then 80mg orally daily on days 2,3 35-39.9kg - 80mg orally daily for 3 doses 20-34.9kg - 40mg orally daily for 3 doses \<20kg - 1.5-2mg/kg orally daily for 3 doses
Olanzapine First, Aprepitant Second	Olanzapine	Will receive olanzapine (weight based dose, see below) in first cycle of chemotherapy and aprepitant (weight based dose, see below) in the second cycle of chemotherapy. All doses will be given starting 30 minutes before chemotherapy on day 1. Olanzapine dosing: \>60kg - 10mg orally daily for 4 doses 40-59.9kg - 5mg orally daily for 4 doses 20-39.9kg - 2.5mg orally daily for 4 doses \<20kg - 1.25mg orally daily for 4 doses Aprepitant dosing: \>40kg - 125mg orally on day 1, then 80mg orally daily on days 2,3 35-39.9kg - 80mg orally daily for 3 doses 20-34.9kg - 40mg orally daily for 3 doses \<20kg - 1.5-2mg/kg orally daily for 3 doses
Aprepitant First, Olanzapine Second	Olanzapine	Will receive aprepitant (weight based dose, see below) in first cycle of chemotherapy and olanzapine (weight based dose, see below) in the second cycle of chemotherapy. All doses will be given starting 30 minutes before chemotherapy on day 1. Olanzapine dosing: \>60kg - 10mg orally daily for 4 doses 40-59.9kg - 5mg orally daily for 4 doses 20-39.9kg - 2.5mg orally daily for 4 doses \<20kg - 1.25mg orally daily for 4 doses Aprepitant dosing: \>40kg - 125mg orally on day 1, then 80mg orally daily on days 2,3 35-39.9kg - 80mg orally daily for 3 doses 20-34.9kg - 40mg orally daily for 3 doses \<20kg - 1.5-2mg/kg orally daily for 3 doses

Primary Outcome Measures

Name	Time	Method
Feasibility of Recruitment and Data Collection.	Approximately 1 year after study opens, at the conclusion of data collection. Participants will be followed during 2 cycles of chemotherapy, an expected average of 6 weeks. Data will be collected over 5 days during each cycle.	Primary objective of this study is to determine the feasibility of recruitment and data collection for conducting a larger trial. Recruitment and data collection will be feasible if at least 20 subjects can be recruited in 1 year and there is a 90% form completion rate.

Secondary Outcome Measures

Name	Time	Method
Complete Response in Acute Phase	Participants will be followed during 2 cycles of chemotherapy, an expected average of 6 weeks. Data will be collected over 5 days during each cycle.	This will measure what percentage of patients have a complete response (no emesis or use of breakthrough medications) in the acute phase (0-24 hours).
Complete Response in Delayed Phase	Participants will be followed during 2 cycles of chemotherapy, an expected average of 6 weeks. Data will be collected over 5 days during each cycle.	This will measure what percentage of patients have a complete response (no emesis or use of breakthrough medications) in the delayed phase (25-120 hours).
Complete Response in Overall Phase	Participants will be followed during 2 cycles of chemotherapy, an expected average of 6 weeks. Data will be collected over 5 days during each cycle.	This will measure what percentage of patients have a complete response (no emesis or use of breakthrough medications) in the overall phase (0-120 hours).
Good Control of Nausea	Participants will be followed during 2 cycles of chemotherapy, an expected average of 6 weeks. Data will be collected over 5 days during each cycle.	Good control of nausea will be ratings \<25 on visual analog scale by parents and \<2 on baxter retching faces scale by patients. Will look at the proportions of patients with good control of nausea. The visual analog scale ranged from 0-100, with 0 being no nausea and 100 being very very severe nausea. The Baxter retching faces scale ranged from 0-10 using only even numbers (0,2,4,6,8,10) and each number has a corresponding face depicting someone experiencing varying levels of nausea, with 0 being no nausea and 10 being a picture of face vomiting.