A Study of the Safety and Efficacy of Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Pediatric Participants (MK-0869-208)

Study Overview
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Brief Summary
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This study will compare the safety and efficacy of a three-day oral aprepitant regimen (aprepitant plus ondansetron) to ondansetron alone in the prevention of chemotherapy-induced nausea and vomiting (CINV) in the 120 hours following the initiation of chemotherapy in pediatric participants. Those who complete this first cycle of treatment and meet certain eligibility criteria will have the option of continuing for 5 additional cycles of open-label aprepitant.

Official Title
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A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Clinical Trial, Conducted Under In-House Blinding Conditions, to Examine the Efficacy and Safety of Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Pediatric Patients

Conditions
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Chemotherapy Induced Nausea and Vomiting

Intervention / Treatment
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* Drug: Aprepitant 125 mg
* Drug: Aprepitant 80 mg
* Drug: Aprepitant powder for suspension (PFS)
* Drug: Ondansetron
* Drug: Placebo for Aprepitant 125 mg
* Drug: Placebo for Aprepitant 80 mg
* Drug: Placebo for Aprepitant PFS
* Drug: Emetogenic chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cycle 1: Is 6 months to 17 years of age at time of study entry Is scheduled to receive chemotherapeutic agent(s) associated with moderate, high risk or very high risk of vomiting for a documented malignancy, or a chemotherapy regimen not previously tolerated due to vomiting Is expected to receive ondansetron as part of their antiemetic regimen If female and has begun menses, must has a negative urine pregnancy test prior to randomization. A female who is of reproductive potential agrees to remain abstinent or use a barrier form of contraception for at least 14 days prior to, throughout, and for at least one month following the last dose of study medication If >10 years old, have a Karnofsky score ≥ 60; if ≤ 10 years have a Lansky Play Performance score ≥ 60 Have a predicted life expectancy of ≥ 3 months Optional Cycles 2-6: Participant has, in the opinion of the investigator, completed the preceding cycle of chemotherapy and related study procedures satisfactorily Exclusion Criteria: Cycle 1: Has vomited in the 24 hours prior to Treatment Day 1 Is scheduled to receive stem cell rescue therapy in conjunction with study related course(s) of emetogenic chemotherapy Has received or will receive radiation therapy to the abdomen or pelvis within a week prior to Treatment Day 1 or during the course of the study Is pregnant or breast feeding Is allergic to aprepitant, ondansetron, or any other 5-hydroxytryptamine type-3 receptor (5-HT3) antagonist Has a symptomatic primary or metastatic CNS malignancy causing nausea and/or vomiting History of QT prolongation or taking other medicinal products that lead to QT prolongation Has an active infection (e.g., pneumonia), congestive heart failure, bradyarrhythmia, or any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction) except for malignancy, which in the opinion of the investigator, might confound the results of the study or pose unwarranted risk in administering study drug to the participant Has had benzodiazepine or opioid therapy initiated within 48 hours of study drug administration, except for single daily doses of triazolam, temazepam, or midazolam Has been started on systemic corticosteroid therapy within 72 hours prior to study drug administration or is planned to receive a corticosteroid as part of the chemotherapy regimen Is currently taking warfarin Optional Cycles 2-6: All exclusion criteria from Cycle 1 apply except for vomiting in the 24 hours prior to Treatment Day 1

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aprepitant Regimen<br>Cycle 1: Participants 12 to 17 years of age, Day 1: aprepitant 125 mg capsule orally (PO) + ondansetron, Days 2 to 3: aprepitant 80 mg capsule PO. Participants 6 months to <12 years of age, Day 1: aprepitant powder for suspension (PFS), 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: aprepitant PFS, 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1. | Drug: Aprepitant 125 mg<br>* On the morning of Day 1: one 125 mg capsule PO 60 minutes prior to chemotherapy for participants 12 to 17 years of age<br>* Other names: MK-0869, Emend®;Drug: Aprepitant 80 mg<br>* On the morning of Days 2 and 3: one 80 mg capsule PO for participants 12 to 17 years of age<br>* Other names: MK-0869, Emend®;Drug: Aprepitant powder for suspension (PFS)<br>* On the morning of Day 1: 3.0 mg/kg (up to 125 mg) PO 60 minutes prior to chemotherapy for participants 6 months to <12 years of age. On the morning of Days 2 and 3: 2.0 mg/kg (up to 80 mg) PO 60 minutes prior to chemotherapy (if applicable) for participants 6 months to <12 years of age<br>* Other names: MK-0869, Emend®;Drug: Ondansetron<br>* Day 1: Administered according to product label for pediatric usage or local standard of care<br>* Other names: Zofran™;Drug: Emetogenic chemotherapy<br>* Any moderately or highly emetic chemotherapeutic agent such as cyclophosphamide, doxorubicin, methotrexate, carboplatin, cisplatin, irinotecan, carmustine, ifosfamide, and streptozocin, or chemotherapeutics of a lower emetogenicity that were not previously tolerated. No chemotherapeutic agents were specified by the protocol, and many could potentially have been used.<br>|
| Placebo Comparator: Control Regimen<br>Cycle 1: Participants 12 to 17 years of age, Day 1: matching placebo for aprepitant 125 mg capsule oral (PO) + ondansetron Days 2 to 3: matching placebo for aprepitant 80 mg capsule PO. Participants 6 months to <12 years of age, Day 1: matching placebo PFS: 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: matching placebo PFS: 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1. | Drug: Ondansetron<br>* Day 1: Administered according to product label for pediatric usage or local standard of care<br>* Other names: Zofran™;Drug: Placebo for Aprepitant 125 mg<br>* On the morning of Day 1: one 125 mg capsule PO 60 minutes prior to chemotherapy for participants 12 to 17 years of age<br>Drug: Placebo for Aprepitant 80 mg<br>* On the morning of Days 2 and 3: one 80 mg capsule PO for participants 12 to 17 years of age<br>Drug: Placebo for Aprepitant PFS<br>* On the morning of Day 1: 3.0 mg/kg (up to 125 mg) PO 60 minutes prior to chemotherapy for participants 6 months to <12 years of age. On the morning of Days 2 and 3: 2.0 mg/kg (up to 80 mg) PO 60 minutes prior to chemotherapy (if applicable) for participants 6 months to <12 years of age<br>Drug: Emetogenic chemotherapy<br>* Any moderately or highly emetic chemotherapeutic agent such as cyclophosphamide, doxorubicin, methotrexate, carboplatin, cisplatin, irinotecan, carmustine, ifosfamide, and streptozocin, or chemotherapeutics of a lower emetogenicity that were not previously tolerated. No chemotherapeutic agents were specified by the protocol, and many could potentially have been used.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Complete Response in the Delayed Phase of Cycle 1 | Delayed Phase was defined as 25-120 hours after the start of chemotherapy. Complete response was defined as no vomiting or retching and no use of rescue medication in the delayed phase of Cycle 1. | 25 to 120 hours after the start of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Complete Response in the Acute Phase of Cycle 1 | Acute phase was defined as 0 to 24 hours after the start of chemotherapy. Complete response was defined as no vomiting or retching and no use of rescue medication in the acute phase of Cycle 1. | 0 to 24 hours after initiation of chemotherapy | 
| Percentage of Participants With a Complete Response in the Overall Phase of Cycle 1 | Overall phase was defined as 0 to 120 hourse after the start of chemotherapy. Complete response was defined as no vomiting or retching and no use of rescue medication in the overall phase of Cycle 1. | 0 to 120 hours after initiation of chemotherapy | 
| Percentage of Participants With No Vomiting in the Overall Phase of Cycle 1 | Overall phase was defined as 0 to 120 hourse after the start of chemotherapy. No vomiting was defined as no emesis or retching or dry heaves in the overall phase of Cycle 1. | 0 to 120 hours after initiation of chemotherapy |