Chemotherapy Induced Nausea and Vomiting
Conditions
Keywords
olanzapine, Nausea and vomiting, aprepitant, pediatrics
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.
Interventions
DRUGOlanzapine
DRUGAprepitant
Sponsors
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 21 Years
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
Olanzapine
Aprepitant | 11 |
| 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
Olanzapine
Aprepitant | 4 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Aprepitant First, Olanzapine Second | Olanzapine First, Aprepitant Second | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 11 Participants | 3 Participants | 14 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Continuous | 10.5 years | 14 years | 11.8 years |
| Chemotherapy Regimen ABVE-PC | 1 participants | 0 participants | 1 participants |
| Chemotherapy Regimen BEACOPP | 1 participants | 0 participants | 1 participants |
| Chemotherapy Regimen CHOP | 0 participants | 1 participants | 1 participants |
| Chemotherapy Regimen Cisplatin/Bleomycin/Etoposide | 1 participants | 0 participants | 1 participants |
| Chemotherapy Regimen Cisplatin/Doxorubicin | 2 participants | 1 participants | 3 participants |
| Chemotherapy Regimen Cisplatin/Etoposide | 2 participants | 0 participants | 2 participants |
| Chemotherapy Regimen Cisplatin/Vincristine | 1 participants | 0 participants | 1 participants |
| Chemotherapy Regimen High Dose Methotrexate | 1 participants | 0 participants | 1 participants |
| Chemotherapy Regimen Vincristine/Cyclophosphamide/Doxorubicin | 2 participants | 2 participants | 4 participants |
| Diagnosis Ewings | 2 participants | 2 participants | 4 participants |
| Diagnosis Germ Cell Tumor | 1 participants | 0 participants | 1 participants |
| Diagnosis Histiocytic Sarcoma | 0 participants | 1 participants | 1 participants |
| Diagnosis Hodgkins | 2 participants | 0 participants | 2 participants |
| Diagnosis Medulloblastoma | 1 participants | 0 participants | 1 participants |
| Diagnosis Neuroblastoma | 2 participants | 0 participants | 2 participants |
| Diagnosis Osteosarcoma | 3 participants | 1 participants | 4 participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 6 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 15 | 2 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Feasibility of Recruitment and Data Collection.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Feasibility of Recruitment and Data Collection. | 70.4 percentage of completed forms |
Secondary
Complete Response in Acute Phase
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Complete Response in Acute Phase | 76.9 percentage of participants with CR |
| Olanzapine | Complete Response in Acute Phase | 78.6 percentage of participants with CR |
Secondary
Complete Response in Delayed Phase
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Complete Response in Delayed Phase | 23.1 percentage of participants with CR |
| Olanzapine | Complete Response in Delayed Phase | 28.6 percentage of participants with CR |
Secondary
Complete Response in Overall Phase
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Complete Response in Overall Phase | 23.1 percentage of participants with CR |
| Olanzapine | Complete Response in Overall Phase | 28.6 percentage of participants with CR |
Secondary
Good Control of Nausea
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.
Population: could only analyze cycles where subjects had returned completed forms
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Good Control of Nausea | Visual Analog Scale/Parents | 54.5 percentage of participant w/good control |
| All Participants | Good Control of Nausea | BARF scale/Patients | 54.5 percentage of participant w/good control |
| Olanzapine | Good Control of Nausea | Visual Analog Scale/Parents | 50 percentage of participant w/good control |
| Olanzapine | Good Control of Nausea | BARF scale/Patients | 50 percentage of participant w/good control |
Other Pre-specified
Number of Participants With Adverse Events.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Number of Participants With Adverse Events. | 0 participants |
| Olanzapine | Number of Participants With Adverse Events. | 0 participants |