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)
Condition: Chemotherapy Induced Nausea and Vomiting
MeSH terms: Nausea; Vomiting
Intervention: Aprepitant 125 mg; Aprepitant 80 mg; Aprepitant powder for suspension (PFS); Ondansetron; Placebo for Aprepitant 125 mg; Placebo for Aprepitant 80 mg; Placebo for Aprepitant PFS; Emetogenic chemotherapy
Intervention description: On the morning of Day 1: one 125 mg capsule PO 60 minutes prior to chemotherapy for participants 12 to 17 years of age; On the morning of Days 2 and 3: one 80 mg capsule PO for participants 12 to 17 years of age; 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; Day 1: Administered according to product label for pediatric usage or local standard of care; On the morning of Day 1: one 125 mg capsule PO 60 minutes prior to chemotherapy for participants 12 to 17 years of age; On the morning of Days 2 and 3: one 80 mg capsule PO for participants 12 to 17 years of age; 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; 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."
Intervention MeSH terms: Ondansetron; Aprepitant; Fosaprepitant
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 307.0
Sex: All
Minimum age: 6 Months
Maximum age: 17 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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