Back to resultsA Study of the Safety and Efficacy of Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Pediatric Participants (MK-0869-208)
Primary Purpose
Chemotherapy Induced Nausea and Vomiting
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
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
Sponsored by
About this trial
This is an interventional prevention trial for Chemotherapy Induced Nausea and Vomiting
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Aprepitant Regimen
Control Regimen
Arm 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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01362530
Brief Title
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
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
September 13, 2011 (Actual)
Primary Completion Date
March 14, 2013 (Actual)
Study Completion Date
August 16, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chemotherapy Induced Nausea and Vomiting
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
307 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Aprepitant Regimen
Arm Type
Experimental
Arm 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.
Arm Title
Control Regimen
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Aprepitant 125 mg
Other Intervention Name(s)
MK-0869, Emend®
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
Intervention Type
Drug
Intervention Name(s)
Aprepitant 80 mg
Other Intervention Name(s)
MK-0869, Emend®
Intervention Description
On the morning of Days 2 and 3: one 80 mg capsule PO for participants 12 to 17 years of age
Intervention Type
Drug
Intervention Name(s)
Aprepitant powder for suspension (PFS)
Other Intervention Name(s)
MK-0869, Emend®
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Ondansetron
Other Intervention Name(s)
Zofran™
Intervention Description
Day 1: Administered according to product label for pediatric usage or local standard of care
Intervention Type
Drug
Intervention Name(s)
Placebo for Aprepitant 125 mg
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
Intervention Type
Drug
Intervention Name(s)
Placebo for Aprepitant 80 mg
Intervention Description
On the morning of Days 2 and 3: one 80 mg capsule PO for participants 12 to 17 years of age
Intervention Type
Drug
Intervention Name(s)
Placebo for Aprepitant PFS
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Emetogenic chemotherapy
Intervention Description
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."
Primary Outcome Measure Information:
Title
Percentage of Participants With a Complete Response in the Delayed Phase of Cycle 1
Description
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.
Time Frame
25 to 120 hours after the start of chemotherapy
Secondary Outcome Measure Information:
Title
Percentage of Participants With a Complete Response in the Acute Phase of Cycle 1
Description
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.
Time Frame
0 to 24 hours after initiation of chemotherapy
Title
Percentage of Participants With a Complete Response in the Overall Phase of Cycle 1
Description
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.
Time Frame
0 to 120 hours after initiation of chemotherapy
Title
Percentage of Participants With No Vomiting in the Overall Phase of Cycle 1
Description
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.
Time Frame
0 to 120 hours after initiation of chemotherapy
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
25770814
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. Erratum In: Lancet Oncol. 2015 Sep;16(9):e427.
Results Reference
result
PubMed Identifier
29893452
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.
Results Reference
derived
Available IPD and Supporting Information:
Available IPD/Information Type
CSR Synopsis
Available IPD/Information URL
http://www.merck.com/clinical-trials/study.html?id=0869-208&kw=0869-208&tab=access
Learn more about this trial
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)
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