Comparative Study of Fosaprepitant and Aprepitant for the Prevention of Chemotherapy-induced Nausea and Vomiting in Pediatric Caner Patients

Study Overview
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Brief Summary
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Children aged 2-12 years scheduled to receive moderately or highly emetogenic chemotherapy were randomly assigned to arm-A (fosaprepitant) or arm-B (aprepitant). Children recruited to arm-A received intravenous granisetron plus dexamethasone followed by fosaprepitant infusion. Children recruited to arm-B received the same drugs as those given to children in arm-A, except that fosaprepitant was substituted with aprepitant. Granisetron and dexamethasone were given continuously until 48 hours after completion of chemotherapy. The primary end point of the study was to determine the proportion of patients who achieved a CR, defined as no vomiting, no retching, and no use of rescue medication, the proportion of patients who achieved a CR during the acute phase (0-24 hours) after administration of the last dose of chemotherapy. Secondary end points were the proportion of patients who achieved a CR during the 24-120 hours (delayed phase) and overall after administration of the last dose of chemotherapy.

Official Title
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Comparative Study of Fosaprepitant and Aprepitant for the Prevention of Chemotherapy-induced Nausea and Vomiting in Pediatric Cancer Patients：A Superiority Design, Phase III Randomized Trial

Conditions
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Chemotherapy Induced Nausea and Vomiting, Pediatric Cancer Patients

Intervention / Treatment
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* Drug: fosaprepitant
* Drug: aprepitant
* Drug: Granisetron plus dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: children aged 2-12 years at the time of study entry with documented cancer scheduled to receive MEC or HEC (more than 30% emetogenic potential) with Karnofsky score of 60 or more (for patients aged greater than 10 years) or Lansky play performance score of 60 or more (for patients aged 10 years or less) predicted life expectancy of at least 3 months; and written informed consent provided by parent or guardian Exclusion Criteria: vomiting 24 hours before treatment day 1 known history of QT prolongation or allergic reaction to any of the study drugs symptomatic primary or metastatic CNS malignancy causing nausea or vomiting patients who received radiation therapy to the abdomen or pelvis in the week before treatment; active infection or any uncontrolled concurrent illness except for malignancy abnormal laboratory values at screening (peripheral absolute neutrophil count <1000 cells per μL, platelet count <100 000 cells per μL; alanine amino transferase or aspartate aminotransferase >5 times of the upper limit of normal for age, bilirubin or serum creatinine >1.5 times of the upper limit of normal for age) initiation of systemic corticosteroids within 72 hours before study drug administration or as part of the chemotherapy regimen; benzodiazepines or opioids initiated within 48 hours before treatment, except for single doses of triazolam, temazepam, or midazolam use of antiemetics within 48 hours of treatment use of CYP3A4 substrates or inhibitors within 7 days or CYP3A4 inducers within 30 days of treatment

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 12 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fosaprepitant<br>Patients received intravenous Granisetron plus dexamethasone followed by fosaprepitant infusion | Drug: fosaprepitant<br>* Granisetron+dexamethasone: granisetron:40mcg/kg, IV ; dexamethasone : S<0.6m2, 2 mg/dose, q12h IV/PO; S>0.6m2, 4 mg/dose, q12h , IV/PO. When used with fosaprepitant, dexamethasone dose was halved. Fosaprepitant: 4 mg/kg IV<br>Drug: Granisetron plus dexamethasone<br>* Granisetron+dexamethasone: granisetron:40mcg/kg, IV ; dexamethasone : S<0.6m2, 2 mg/dose, q12h IV/PO; S>0.6m2, 4 mg/dose, q12h , IV/PO.<br>|
| Experimental: Aprepitant<br>Patients received intravenous Granisetron plus dexamethasone followed by oral aprepitant | Drug: aprepitant<br>* Granisetron+dexamethasone: granisetron:40mcg/kg, IV ; dexamethasone : S<0.6m2, 2 mg/dose, q12h IV/PO; S>0.6m2, 4 mg/dose, q12h , IV/PO. When used with aprepitant, dexamethasone dose was halved. Oral aprepitant: D1：Powder for suspension 3.0 mg/kg (up to 125 mg),D2，D3：Powder for suspension 2.0 mg/kg (up to 80 mg).<br>Drug: Granisetron plus dexamethasone<br>* Granisetron+dexamethasone: granisetron:40mcg/kg, IV ; dexamethasone : S<0.6m2, 2 mg/dose, q12h IV/PO; S>0.6m2, 4 mg/dose, q12h , IV/PO.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission rates in the acute phases | The primary end point was complete remission rates in the acute phase. Complete Remission was defined as no vomiting, no retching, and no use of rescue medication | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission rates in the delayed and overall phases | Complete Remission rates in the delayed and overall phases | up to 6 months | 
| Adverse events reported in study patients | All of the adverse reactions of aprepitant and fosaprepitant during the study. | up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fosaprepitant, aprepitant, pediatric cancer, vomiting, efficacy, safety