Efficacy of Aprepitant (Emend®) in Children

Study Overview
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Brief Summary
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The purpose of this study is to find out whether or not adding aprepitant(Emend®) to the standard therapy will help children who receive chemotherapy to have less nausea and vomiting.

Detailed Description
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1.1 Primary Aim To determine the efficacy of aprepitant (Emend®) in preventing and reducing chemotherapy-induced nausea and vomiting (CINV) when added to standard antiemetic drug regimens for children receiving highly emetogenic chemotherapy. The working hypothesis will be that standard therapy + aprepitant is superior at preventing CINV than standard therapy + placebo. 1.2 Secondary Aim To evaluate the safety and toxicity of aprepitant (Emend®) in children receiving highly emetogenic chemotherapy when compared to standard antiemetic therapy + placebo.

Official Title
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Efficacy of Aprepitant (Emend®) in Children Receiving Highly Emetogenic Chemotherapy

Conditions
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Nausea, Vomiting, Childhood Cancer

Intervention / Treatment
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* Drug: Ondansetron, dexamethasone, aprepitant
* Drug: Ondansetron, Dexamethasone, placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: under 20.99 years of age at enrollment Scheduled to receive two identical cycles of highly emetogenic[1] chemotherapy for treatment of a primary malignancy, including: Chemotherapy with any one or more of the following single agents in any combination: Carboplatin Carmustine >250 mg/m2 Cisplatin Cyclophosphamide ≥1 g/m2 Dactinomycin High dose Methotrexate ≥ 5 g/m2 Or any of the following defined combinations: Cyclophosphamide + anthracycline Cyclophosphamide + etoposide Cytarabine 150-200 mg/m2 + daunorubicin Cytarabine 300 mg/m2 + etoposide Cytarabine 300 mg/m2 + teniposide Doxorubicin + ifosfamide Doxorubicin + methotrexate 5 g/m2 Etoposide + ifosfamide Exclusion Criteria: Patients who have received aprepitant in the past. Patients who demonstrate evidence of increased intracranial pressure.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ondansetron, dexamethasone, aprepitant<br>Arm A: Ondansetron 0.15 mg/kg (max 16 mg) IV or PO every 8 hours for at least 3 days, but no longer than 5 days; dexamethasone 0.2mg/kg (max 10 mg) IV or PO daily for at least 3 days, but no longer than 5 days; and aprepitant 3 mg/kg (max 125 mg) PO on day 1, and aprepitant 2 mg/kg (max 80 mg) PO on days 2 and 3 during the first investigational antiemetic cycle. During the next investigational antiemetic cycle, members of this arm will be crossed-over into the placebo arm, where the aprepitant will be replaced by placebo and the dexamethasone dose will be increased to 0.4 mg/kg (max 20 mg) daily. | Drug: Ondansetron, dexamethasone, aprepitant<br>* Ondansetron 0.15 mg/kg (max 16 mg) IV or PO every 8 hours for at least 3 days, but no longer than 5 days; dexamethasone 0.2mg/kg (max 10 mg) IV or PO daily for at least 3 days, but no longer than 5 days; and aprepitant 3 mg/kg (max 125 mg) PO on day 1, and aprepitant 2 mg/kg (max 80 mg) PO on days 2 and 3 during the first investigational antiemetic cycle. During the next investigational antiemetic cycle, members of this arm will be crossed-over into the placebo arm, where the aprepitant will be replaced by placebo and the dexamethasone dose will be increased to 0.4 mg/kg (max 20 mg) daily.<br>* Other names: ARM A;|
| Placebo Comparator: Ondansetron, Dexamethasone, placebo<br>Arm B: Ondansetron 0.15 mg/kg (max 16 mg) IV or PO every 8 hours for at least 3 days, but no more than 5 days; dexamethasone 0.4 mg/kg (max 20 mg) IV or PO daily for at least 3 days, but no more than 5 days; and a PO placebo for 3 days during the first investigational antiemetic cycle. During the second cycle, members this group will be crossed-over to the experimental arm, where the placebo will be replaced by aprepitant and the dexamethasone will be decreased by 50%. | Drug: Ondansetron, Dexamethasone, placebo<br>* Ondansetron 0.15 mg/kg (max 16 mg) IV or PO every 8 hours for at least 3 days, but no more than 5 days; dexamethasone 0.4 mg/kg (max 20 mg) IV or PO daily for at least 3 days, but no more than 5 days; and a PO placebo for 3 days during the first investigational antiemetic cycle. During the second cycle, members this group will be crossed-over to the experimental arm, where the placebo will be replaced by aprepitant and the dexamethasone will be decreased by 50%.<br>* Other names: ARM B;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of aprepitant (Emend®) measured through a complete response | • Percentage of study subjects who demonstrate a complete response, defined as no episodes of emesis and no use of rescue medications during the investigational antiemetic cycles. | Up to 11 weeks, or until 3 weeks after the second course of the study regimen | 
| Efficacy of aprepitant (Emend®) measured through episodes of emesis and use of rescue medication. | The total episodes of emesis within 7 days of the first chemotherapy administration of each cycle. The total number of administrations of rescue medications given for breakthrough nausea or vomiting. | Up to 11 weeks, or until 3 weeks after the second course of the study regimen | 
| Efficacy of aprepitant (Emend®) measured through impact of chemotherapy induced nausea and vomiting on daily life | • A modified, 5-day recall version of the Functional Living Index-Emesis (FLIE) questionnaire | Up to 11 weeks, or until 3 weeks after the second course of the study regimen | 
| Efficacy of aprepitant (Emend®) measured through a pictorial nausea scale | • A modified version of the Baxter Animated Retching Faces (BARF) scale, administered daily. | Up to 11 weeks, or until 3 weeks after the second course of the study regimen | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of aprepitant (Emend®) | Occurrence of adverse events as per the NCI Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. These will be reported spontaneously or on inquiry by the investigator/study nurse, and continuously monitored throughout the trial. Weekly complete blood count (CBC) for 3 weeks after each investigational antiemetic cycle. Weekly complete metabolic profile (CMP) for 3 weeks after each investigational antiemetic cycle. | Up to 11 weeks, or until 3 weeks after the second course of the study regimen | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vomiting, Children, Aprepitant, Emend®, Nausea