Safety of a Three-Day Fosaprepitant Regimen for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Pediatric Participants (MK-0517-045)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of a 3-day intravenous (IV) fosaprepitant dimeglumine (MK-0517) regimen for the prevention of CINV in pediatric participants scheduled to receive emetogenic chemotherapy. Each participant was enrolled in Cycle 1 (on which the primary study objectives were based), consisting of the 3-day treatment cycle and 14 days of follow-up for a total of 17 days.

Detailed Description
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Upon completion of Cycle 1, participants were given the option to exit the study and be considered completed, or to continue on study therapy for up to 2 more (optional) 17-day cycles of chemotherapy where fosaprepitant was administered and additional safety data collected.

Official Title
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A Phase 4, Open-label, Single Arm Study to Evaluate the Safety and Tolerability of a Three-day Fosaprepitant Regimen Administered for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Pediatric Participants Receiving Emetogenic Chemotherapy

Conditions
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Chemotherapy-induced Nausea and Vomiting

Intervention / Treatment
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* Drug: Fosaprepitant Dimeglumine
* Drug: 5-HT3 antagonist
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is receiving a moderately or highly emetogenic chemotherapy agent/regimen or a chemotherapy agent/regimen not previously tolerated due to vomiting Has a Lansky Play Performance score ≥60 (participants ≤16 years of age) or a Karnofsky score ≥60 (participants >16 years of age) Has a pre-existing functional central venous catheter available for study treatment administration Is fosaprepitant naïve Has a predicted life expectancy ≥3 months A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP) OR is a WOCBP and agrees to not be sexually active or use a highly effective contraceptive method for at least 28 days prior to receiving study treatment, during the treatment period, and for at least 30 days (or local standard of care if longer) after the last dose of study treatment (including the optional cycles) Has a negative highly sensitive pregnancy test (urine or serum as required by local regulations) prior to the start of fosaprepitant administration in a given cycle if a WOCBP Weighs at least 6 kilograms (kg) Exclusion Criteria: Will receive stem cell rescue therapy in conjunction with a study-related course of emetogenic chemotherapy or during the 14 days following administration of fosaprepitant Is currently a user of any recreational or illicit drugs or has current evidence of drug or alcohol abuse or dependence as determined by the investigator Is mentally incapacitated or has a significant emotional or psychiatric disorder that, in the opinion of the investigator, precludes study entry Is pregnant or breast feeding Is allergic to fosaprepitant, aprepitant, or prescribed 5-HT3 antagonist Has an active infection (eg, pneumonia), congestive heart failure, bradyarrhythmia, any uncontrolled disease (eg, diabetic ketoacidosis, gastrointestinal obstruction) except for malignancy, or has any illness which in the opinion of the investigator, might confound the results of the study or pose unwarranted risk in administering study treatment or concomitant therapy to the participant Is a WOCBP who has a positive pregnancy test at screening (Cycle 1) or on Day 1 of optional Cycles 2 or 3 Has been started on systemic corticosteroid therapy within 72 hours prior to study treatment administration or is expected to receive a corticosteroid as part of the chemotherapy regimen. Exceptions apply Is taking excluded medications Has ever participated in a previous study of aprepitant or fosaprepitant or has taken a non-approved (investigational) drug within the last 4 weeks Has a known history of QT prolongation or is taking any medication that is known to lead to QT prolongation

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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fosaprepitant Treatment<br>Participants received fosaprepitant dimeglumine once daily (QD) for 3 days and were followed for 14 days during the 17-day Cycle 1. Participants also optionally received dexamethasone as background therapy, and a serotonin (5-hydroxytryptamine [5-HT3]) receptor antagonist on Day 1 and optionally on Days 2-3 as background therapy. After completing Cycle 1, participants had the option to continue for up to 2 additional 17-day cycles of the same treatment regimen. | Drug: Fosaprepitant Dimeglumine<br>* Participants received IV fosaprepitant dimeglumine ≤115 mg on Day 1 and ≤80 mg on Days 2 and 3 (dose adjusted for age).<br>* Other names: MK-0517;Drug: 5-HT3 antagonist<br>* All participants received an oral 5-hydroxytryptamine (serotonin; [5-HT]) 3 receptor antagonist on Day 1 and had the option to take on Days 2-3. The dose was as per product label or standard of care.<br>Drug: Dexamethasone<br>* Participants received optional oral dexamethasone at the investigator's discretion according to product label or standard of care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Cycle 1 Who Experienced One or More Adverse Events (AEs) | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. The percentage of participants in Cycle 1 who experience one or more AE(s) is presented. | Up to 17 days | 
| Percentage of Participants in Cycle 1 Who Discontinued Study Drug Due to an Adverse Event (AE) | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. The percentage of participants in Cycle 1 who discontinue study treatment due to an AE is presented. | Up to 3 days |