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)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Chemotherapy Induced Nausea and Vomiting

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01362530

0869-208

Details and patient eligibility

About

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.

Enrollment: 307 patients

Sex: All

Ages: 6 months to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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307 participants in 2 patient groups, including a placebo group

Aprepitant Regimen

Experimental group

Description:

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.

Treatment:

Drug: Ondansetron

Drug: Aprepitant 80 mg

Drug: Emetogenic chemotherapy

Drug: Aprepitant powder for suspension (PFS)

Drug: Aprepitant 125 mg

Control Regimen

Placebo Comparator group

Description:

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.

Treatment:

Drug: Ondansetron

Drug: Emetogenic chemotherapy

Drug: Placebo for Aprepitant 125 mg

Drug: Placebo for Aprepitant 80 mg

Drug: Placebo for Aprepitant PFS