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)

Phase 3

Completed

Conditions: Chemotherapy Induced Nausea and Vomiting

Interventions: Drug: Aprepitant 125 mg
Drug: Aprepitant 80 mg
Drug: Placebo for Aprepitant 125 mg
Drug: Placebo for Aprepitant 80 mg
Drug: Aprepitant powder for suspension (PFS)
Drug: Ondansetron
Drug: Placebo for Aprepitant PFS
Drug: Emetogenic chemotherapy

Registration Number: NCT01362530

Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 307

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aprepitant Regimen	Aprepitant 80 mg	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.
Aprepitant Regimen	Ondansetron	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.
Aprepitant Regimen	Emetogenic chemotherapy	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.
Control Regimen	Placebo for Aprepitant 125 mg	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.
Control Regimen	Placebo for Aprepitant 80 mg	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.
Control Regimen	Placebo for Aprepitant PFS	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.
Control Regimen	Emetogenic chemotherapy	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.
Aprepitant Regimen	Aprepitant 125 mg	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.
Aprepitant Regimen	Aprepitant powder for suspension (PFS)	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.
Control Regimen	Ondansetron	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With a Complete Response in the Delayed Phase of Cycle 1	25 to 120 hours after the start of chemotherapy	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With a Complete Response in the Acute Phase of Cycle 1	0 to 24 hours after initiation of chemotherapy	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.
Percentage of Participants With a Complete Response in the Overall Phase of Cycle 1	0 to 120 hours after initiation of chemotherapy	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.
Percentage of Participants With No Vomiting in the Overall Phase of Cycle 1	0 to 120 hours after initiation of chemotherapy	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.