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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Indiana University
Sponsor:
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT02097823
First received: March 21, 2014
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Chemotherapy Induced Nausea and Vomiting
Drug: Olanzapine
Drug: Aprepitant
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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:
  • 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. ] [ Designated as safety issue: No ]
    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).

  • 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. ] [ Designated as safety issue: No ]
    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 [ 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. ] [ Designated as safety issue: No ]
    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).

  • 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. ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]
    Olanzapine will be considered tolerable if less than 10% of patients experience a grade III or IV adverse event attributable to olanzapine.

  • Oral intake of patients during chemotherapy cycles [ 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. ] [ Designated as safety issue: No ]
    Will record total oral intake of patients receiving chemotherapy while inpatient.

  • Number of patients requiring IV fluid hydration at home [ 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. ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: February 2014
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   4 Years to 21 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02097823

Contacts
Contact: Catherine Long, MD 317-944-8784 cathlong@iupui.edu

Locations
United States, Indiana
Riley Hospital for Children at Indiana University Health Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Catherine Long, MD    317-944-8784    cathlong@iupui.edu   
Sub-Investigator: Catherine Long, MD         
Sponsors and Collaborators
Indiana University
Investigators
Principal Investigator: Holly Knoderer, MD Indiana University
  More Information

No publications provided

Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT02097823     History of Changes
Other Study ID Numbers: 1401283326
Study First Received: March 21, 2014
Last Updated: March 24, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Indiana University:
olanzapine
Nausea and vomiting
aprepitant
pediatrics

Additional relevant MeSH terms:
Vomiting
Nausea
Signs and Symptoms
Signs and Symptoms, Digestive
Aprepitant
Fosaprepitant
Olanzapine
Antiemetics
Antipsychotic Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Neurokinin-1 Receptor Antagonists
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 22, 2014