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

• Sponsor: Indiana University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02097823
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arms: 2
• Duration (Months): 12.9
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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

• Study Type: Interventional
• 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: Feb 1, 2014
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

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 Names: zyprexa ; Drug: Aprepitant; Other Names: 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 Names: zyprexa ; Drug: Aprepitant; Other Names: emend

Outcome Measures

Primary Outcome Measures

1. 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

1. 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).

2. 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).

3. 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).

4. 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.

Other Outcome Measures

1. Number of Participants With Adverse Events. [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

Criteria

• Ages Eligible for Study: 4 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Holly M. Knoderer, M.D., Indiana University
• ClinicalTrials.gov Identifier: NCT02097823
• Other Study ID Numbers: 1401283326
• First Posted: Mar 27, 2014
• Last Update Posted: Mar 30, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by Holly M. Knoderer, M.D., Indiana University: olanzapine; Nausea and vomiting; aprepitant; pediatrics
• Additional relevant MeSH terms: Nausea; Vomiting; Olanzapine; Aprepitant

Study Results

Participant Flow

Arm/Group Title	Aprepitant First, Olanzapine Second	Olanzapine First, Aprepitant Second
Arm/Group 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 Olanzapine 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 Olanzapine Aprepitant
Period Title: Overall Study
STARTED	11	4
COMPLETED	10	3
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Aprepitant First, Olanzapine Second	Olanzapine First, Aprepitant Second	Total
Arm/Group 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 Olanzapine 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 Olanzapine Aprepitant	Total of all reporting groups
Overall Participants	11	4	15
Age (Count of Participants)
<=18 years	11 100%	3 75%	14 93.3%
Between 18 and 65 years	0 0%	1 25%	1 6.7%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	10.5	14	11.8
Sex: Female, Male (Count of Participants)
Female	5 45.5%	2 50%	7 46.7%
Male	6 54.5%	2 50%	8 53.3%
Diagnosis (participants) [Number]
Ewings	2 18.2%	2 50%	4 26.7%
Osteosarcoma	3 27.3%	1 25%	4 26.7%
Neuroblastoma	2 18.2%	0 0%	2 13.3%
Hodgkins	2 18.2%	0 0%	2 13.3%
Germ Cell Tumor	1 9.1%	0 0%	1 6.7%
Histiocytic Sarcoma	0 0%	1 25%	1 6.7%
Medulloblastoma	1 9.1%	0 0%	1 6.7%
Chemotherapy Regimen (participants) [Number]
Vincristine/Cyclophosphamide/Doxorubicin	2 18.2%	2 50%	4 26.7%
Cisplatin/Doxorubicin	2 18.2%	1 25%	3 20%
High Dose Methotrexate	1 9.1%	0 0%	1 6.7%
Cisplatin/Etoposide	2 18.2%	0 0%	2 13.3%
BEACOPP	1 9.1%	0 0%	1 6.7%
ABVE-PC	1 9.1%	0 0%	1 6.7%
Cisplatin/Bleomycin/Etoposide	1 9.1%	0 0%	1 6.7%
CHOP	0 0%	1 25%	1 6.7%
Cisplatin/Vincristine	1 9.1%	0 0%	1 6.7%

Outcome Measures

1. Primary Outcome

Title	Feasibility of Recruitment and Data Collection.
Description	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.
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Participants
Arm/Group Description	Both intervention arms included
Measure Participants	14
Measure Administered forms	27
Number [percentage of completed forms]	70.4

2. Secondary Outcome

Title	Complete Response in Overall Phase
Description	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).
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aprepitant	Olanzapine
Arm/Group Description	Cycles where patients received aprepitant along with dexamethasone and ondansetron (regardless of whether cycle 1 or cycle 2)	Cycles where patients received olanzapine along with dexamethasone and ondansetron (regardless of whether cycle 1 or cycle 2)
Measure Participants	13	14
Number [percentage of participants with CR]	23.1 210%	28.6 715%

3. Secondary Outcome

Title	Complete Response in Acute Phase
Description	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).
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aprepitant	Olanzapine
Arm/Group Description	Cycles where patients received aprepitant along with dexamethasone and ondansetron (regardless of whether cycle 1 or cycle 2)	Cycles where patients received olanzapine along with dexamethasone and ondansetron (regardless of whether cycle 1 or cycle 2)
Measure Participants	13	14
Number [percentage of participants with CR]	76.9 699.1%	78.6 1965%

4. Secondary Outcome

Title	Complete Response in Delayed Phase
Description	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).
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aprepitant	Olanzapine
Arm/Group Description	Cycles where patients received aprepitant along with dexamethasone and ondansetron (regardless of whether cycle 1 or cycle 2)	Cycles where patients received olanzapine along with dexamethasone and ondansetron (regardless of whether cycle 1 or cycle 2)
Measure Participants	13	14
Number [percentage of participants with CR]	23.1 210%	28.6 715%

5. Secondary Outcome

Title	Good Control of Nausea
Description	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.
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.

Outcome Measure Data

Analysis Population Description

could only analyze cycles where subjects had returned completed forms

Arm/Group Title	Aprepitant	Olanzapine
Arm/Group Description	Cycles where patients received aprepitant along with dexamethasone and ondansetron (regardless of whether cycle 1 or cycle 2)	Cycles where patients received olanzapine along with dexamethasone and ondansetron (regardless of whether cycle 1 or cycle 2)
Measure Participants	11	8
Visual Analog Scale/Parents	54.5	50
BARF scale/Patients	54.5	50

6. Other Pre-specified Outcome

Title	Number of Participants With Adverse Events.
Description	Olanzapine will be considered tolerable if less than 10% of patients experience a grade III or IV adverse event attributable to olanzapine.
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aprepitant	Olanzapine
Arm/Group Description	Cycles where patients received aprepitant along with dexamethasone and ondansetron (regardless of whether cycle 1 or cycle 2)	Cycles where patients received olanzapine along with dexamethasone and ondansetron (regardless of whether cycle 1 or cycle 2)
Measure Participants	13	14
Number [participants]	0 0%	0 0%

Adverse Events

Arm/Group Title	Aprepitant		Olanzapine
Arm/Group Description	Cycles where patients received aprepitant along with dexamethasone and ondansetron (regardless of whether cycle 1 or cycle 2)		Cycles where patients received olanzapine along with dexamethasone and ondansetron (regardless of whether cycle 1 or cycle 2)
All Cause Mortality
	Aprepitant		Olanzapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Aprepitant		Olanzapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Aprepitant		Olanzapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		2/15 (13.3%)
Psychiatric disorders
Agitation	0/15 (0%)	0	2/15 (13.3%)	2

Limitations/Caveats

This trial was a pilot study, limited by numbers of participants. Given the small numbers, during randomization (with 50/50 chance each subject randomized to group A or B) a disproportionate number of patients were randomized to group A.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.