A Pilot Study Comparing Olanzapine and Aprepitant for the Prevention of Chemotherapy Induced Nausea and Vomiting in Pediatric Patients Receiving Highly Emetogenic Chemotherapy

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

Sponsors

Lead sponsor: Indiana University

Source 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.

Overall Status Completed
Start Date February 2014
Completion Date March 2015
Primary Completion Date February 2015
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
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.
Secondary Outcome
Measure Time Frame
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.
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.
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.
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.
Enrollment 15
Condition
Intervention

Intervention type: Drug

Intervention name: Olanzapine

Other name: zyprexa

Intervention type: Drug

Intervention name: Aprepitant

Other name: emend

Eligibility

Criteria:

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)

Gender: All

Minimum age: 4 Years

Maximum age: 21 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Holly Knoderer, MD Principal Investigator Indiana University
Location
facility
Riley Hospital for Children at Indiana University Health
Location Countries

United States

Verification Date

February 2017

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: Indiana University

Investigator full name: Holly M. Knoderer

Investigator title: M.D.

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Aprepitant First, Olanzapine Second

Arm group type: Experimental

Description: 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

Arm group label: Olanzapine First, Aprepitant Second

Arm group type: Experimental

Description: 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

Study Design Info

Allocation: Randomized

Intervention model: Crossover Assignment

Primary purpose: Supportive Care

Masking: None (Open Label)

Source: ClinicalTrials.gov