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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Chemotherapy Induced Nausea and Vomiting	Drug: Olanzapine; Drug: Aprepitant	Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	15 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	None (Open Label)
Primary Purpose:	Supportive Care
Official Title:	A Pilot Study Comparing Olanzapine and Aprepitant for the Prevention of Chemotherapy Induced Nausea and Vomiting in Pediatric Patients Receiving Highly Emetogenic Chemotherapy
Study Start Date :	February 2014
Actual Primary Completion Date :	February 2015
Actual Study Completion Date :	March 2015

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Aprepitant First, Olanzapine Second; 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	Drug: Olanzapine; Other Name: zyprexa Drug: Aprepitant; Other Name: emend
Experimental: Olanzapine First, Aprepitant Second; 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	Drug: Olanzapine; Other Name: zyprexa Drug: Aprepitant; Other Name: emend

Outcome Measures

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Primary Outcome Measures :

1. Feasibility of Recruitment and Data Collection. [ Time Frame: 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 :

1. Complete Response in Overall Phase [ Time Frame: 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).
2. Complete Response in Acute Phase [ Time Frame: 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).
3. Complete Response in Delayed Phase [ Time Frame: 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).
4. Good Control of Nausea [ Time Frame: 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.

Other Outcome Measures:

1. Number of Participants With Adverse Events. [ Time Frame: Ongoing, throughout the study. Will be fully evaluated in approximately 1 year, at the conclusion of data collection. Each patient will be followed during 2 cycles of chemotherapy, an expected average of 6 weeks. ]
   Olanzapine will be considered tolerable if less than 10% of patients experience a grade III or IV adverse event attributable to olanzapine.

Eligibility Criteria

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Ages Eligible for Study:	4 Years to 21 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Indiana
Riley Hospital for Children at Indiana University Health
Indianapolis, Indiana, United States, 46202

Sponsors and Collaborators

Indiana University

Investigators

Principal Investigator:	Holly Knoderer, MD	Indiana University

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Holly M. Knoderer, M.D., Indiana University
ClinicalTrials.gov Identifier:	NCT02097823 History of Changes
Other Study ID Numbers:	1401283326
First Posted:	March 27, 2014
Results First Posted:	March 30, 2017
Last Update Posted:	March 30, 2017
Last Verified:	February 2017

Keywords provided by Holly M. Knoderer, Indiana University:

olanzapine; Nausea and vomiting; aprepitant; pediatrics

Additional relevant MeSH terms:

Nausea; Vomiting; Signs and Symptoms, Digestive; Signs and Symptoms; Olanzapine; Aprepitant; Fosaprepitant; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents	Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Neurokinin-1 Receptor Antagonists