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)

Chemotherapy Induced Nausea and Vomiting Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01362530
• Other study ID #: 0869-208
• Status: Completed
• Phase: Phase 3
• Start date: September 13, 2011
• Est. completion date: August 16, 2013

Study information

• Verified date: August 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 307
• Est. completion date: August 16, 2013
• Est. primary completion date: March 14, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Chemotherapy Induced Nausea and Vomiting
• Nausea
• Vomiting

Intervention

Drug:
• Aprepitant 125 mg
On the morning of Day 1: one 125 mg capsule PO 60 minutes prior to chemotherapy for participants 12 to 17 years of age
• Aprepitant 80 mg
On the morning of Days 2 and 3: one 80 mg capsule PO for participants 12 to 17 years of age
• Aprepitant powder for suspension (PFS)
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
• Ondansetron
Day 1: Administered according to product label for pediatric usage or local standard of care
• Placebo for Aprepitant 125 mg
On the morning of Day 1: one 125 mg capsule PO 60 minutes prior to chemotherapy for participants 12 to 17 years of age
• Placebo for Aprepitant 80 mg
On the morning of Days 2 and 3: one 80 mg capsule PO for participants 12 to 17 years of age
• Placebo for Aprepitant PFS
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
• Emetogenic chemotherapy
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."

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	25 to 120 hours after the start of chemotherapy
Secondary	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.	0 to 24 hours after initiation of chemotherapy
Secondary	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.	0 to 120 hours after initiation of chemotherapy
Secondary	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.	0 to 120 hours after initiation of chemotherapy