Fosaprepitant for the Prevention of Chemotherapy-induced Nausea and Vomiting in Pediatric Patients

Study Overview
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Brief Summary
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The purpose is to evaluate the effectiveness and safety of fosaprepitant plus ondansetron with dexamethasone or placebo plus ondansetron with dexamethasone in preventing chemotherapy-induced nausea and vomiting (CINV) with MEC/HE multi-day chemotherapy in children with solid tumors.

Detailed Description
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Participants will randomly assigned 1:1 to receive double-blind study drug ( fosaprepitant plus ondansetron with dexamethasone OR placebo to fosaprepitant plus ondansetron with dexamethasone). Fosaprepitant or placebo to fosaprepitant were supplied and administered in a blinded manner. Experimental: Participants received a single dose of fosaprepitant (age-based adjustment) administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron (weight based) IV with dexamethasone (weight based) iv/po prior to chemotherapy and up to 72 hours after chemotherapy. Placebo Comparator: Participants received a single dose of matched placebo for fosaprepitant administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron (weight based) IV with dexamethasone (weight based) iv/po prior to chemotherapy and up to 72 hours after chemotherapy.

Official Title
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Efficacy, Safety and Feasibility of Fosaprepitant for the Prevention of Chemotherapy-induced Nausea and Vomiting in Pediatric Patients With Solid Tumors Receiving Moderately and Highly Emetogenic Chemotherapy

Conditions
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Pediatric Cancer

Intervention / Treatment
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* Drug: Fosaprepitant
* Drug: placebo ondansetron with dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is 6 months to 17 years of age at time of randomization; Participants with solid tumors receiving multi -day chemotherapy associated with moderate or high risk of emetogenicity; Has a preexisting functional central venous catheter available for study drug administration; PS score ≤ 2 points; Has a predicted life expectancy ≥3 months or weight greater than 6Kg; Patient's parent or guardian signs informed consent. Exclusion Criteria: Has vomited in the 24 hours prior to chemotherapy initiation on Treatment Day 1; Has a symptomatic primary or metastatic central nervous system (CNS) malignancy with nausea and/or vomiting (asymptomatic participants may participate in study); Will be receiving stem cell rescue therapy in conjunction with study-related course of emetogenic chemotherapy or during the 14 days following administration of fosaprepitant/placebo for fosaprepitant; Has received or will receive total body irradiation of radiation therapy to the abdomen or pelvis in the week prior to Treatment Day 1 and/or during the diary reporting period (120 hours following initiation of chemotherapy); Has had benzodiazepine, opioid or opioid like therapy initiated within 48 hours prior to study drug administration, or is expected to receive within 120 hours following initiation of chemotherapy except for single doses of midazolam, temazepam or triazolam; Has started on systemic corticosteroid therapy within 72 hours prior to study drug administration or is expected to receive a corticosteroid as part of the chemotherapy regimen Is currently taking, or has taken within 48 hours of Treatment Day 1 the following drugs with antiemetic properties: 5-hydroxytryptamine 3 (5-HT3) antagonists (e.g., ondansetron), benzamides (e.g., haloperidol), cyclizine, domperidone, herbal therapies with potential antiemetic properties, olanzapine, phenothiazines (e.g., prochlorpenzine), scopolamine (this is not an exhaustive list); Is currently a user of any recreational or illicit drugs (including marijuana) or has current evidence of drug or alcohol abuse or dependence; Is mentally incapacitated or has a significant emotional or psychiatric disorder; Is allergic to fosaprepitant, aprepitant (MK-0869), ondansetron, or any other 5-HT3 antagonist; Has a known history of QT prolongation or is taking any medication that is known to lead to QT prolongation; Has an active infection (e.g., pneumonia), congestive heart failure, bradyarrhythmia, any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction) except for malignancy; Has ever participated in a previous study of aprepitant or fosaprepitant or has taken an investigational drug with the last 4 weeks; Abnormal liver function (alanine aminotransferase or aspartate aminotransferase ≥ 2 times higher than the upper bound of the normal value) or abnormal renal function (serum creatinine ≥ 2.5 times higher than the upper bound of the normal value); Has participated in a preliminary study of Aprepitant or Fosapretan, or took the study drug in the past 4 weeks; Other situations that the researcher thinks cannot be included.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 17 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: a single dose of fosaprepitant<br>Participants received a single dose of fosaprepitant (age-based adjustment) administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron (weight based) IV with dexamethasone (weight based) iv/po prior to chemotherapy and up to 72 hours after chemotherapy. | Drug: Fosaprepitant<br>* Participants will randomly assigned 1:1 to receive double-blind study drug ( fosaprepitant plus ondansetron with dexamethasone OR placebo plus ondansetron with dexamethasone). Fosaprepitant or placebo to fosaprepitant were supplied and administered in a blinded manner.<br>* Other names: ondansetron, dexamethasone;|
| Placebo Comparator: a single dose of matched placebo<br>Participants received a single dose of matched placebo for fosaprepitant administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron (weight based) IV with dexamethasone (weight based) iv/po prior to chemotherapy and up to 72 hours after chemotherapy. | Drug: placebo ondansetron with dexamethasone<br>* placebo plus ondansetron with dexamethasone<br>* Other names: ondansetron, dexamethasone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CR rate | Percentage of participants who experienced a complete response (CR; no vomiting/rescue medication) rate in overall phases. | between 0 and 120 hours after the start of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CR rate in acute phase | Complete response rate in acute phase | 0 to 24 Hours Post Initiation of Chemotherapy | 
| CR rate in delayed phase | Complete response rate in delayed phase | 25 to 120 Hours Post Initiation of Chemotherapy |