Clinical trial NCT01362530: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chemotherapy Induced Nausea and Vomiting
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-05-30
Enrollment: 307
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: Percentage of Participants With a Complete Response in the Delayed Phase of Cycle 1
timeFrame: 25 to 120 hours after the start of chemotherapy
Secondary outcomes:
measure: Percentage of Participants With a Complete Response in the Acute Phase of Cycle 1
timeFrame: 0 to 24 hours after initiation of chemotherapy
measure: Percentage of Participants With a Complete Response in the Overall Phase of Cycle 1
timeFrame: 0 to 120 hours after initiation of chemotherapy
measure: Percentage of Participants With No Vomiting in the Overall Phase of Cycle 1
timeFrame: 0 to 120 hours after initiation of chemotherapy
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Kang HJ, Loftus S, Taylor A, DiCristina C, Green S, Zwaan CM. Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015 Apr;16(4):385-94. doi: 10.1016/S1470-2045(15)70061-6. Epub 2015 Mar 12.
citation: Kang HJ, Loftus S, DiCristina C, Green S, Pong A, Zwaan CM. Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in paediatric subjects: An analysis by age group. Pediatr Blood Cancer. 2018 Oct;65(10):e27273. doi: 10.1002/pbc.27273. Epub 2018 Jun 12.