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)

NCT01362530 | Completed Phase 3 Results

• 1 other identifier: 0869-208
• Study Type: interventional
• Target: 307
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Chemotherapy Induced Nausea and Vomiting

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Percentage of Participants With a Complete Response in the Acute Phase of Cycle 1

  0 to 24 hours after initiation of chemotherapy

• Percentage of Participants With a Complete Response in the Overall Phase of Cycle 1

  0 to 120 hours after initiation of chemotherapy

• Percentage of Participants With No Vomiting in the Overall Phase of Cycle 1

  0 to 120 hours after initiation of chemotherapy

Study Arms (2)

Aprepitant Regimen

EXPERIMENTAL

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.

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

Control Regimen

PLACEBO COMPARATOR

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.

Drug: Ondansetron; Drug: Placebo for Aprepitant 125 mg; Drug: Placebo for Aprepitant 80 mg; Drug: Placebo for Aprepitant PFS; Drug: Emetogenic chemotherapy

Interventions

Aprepitant 125 mg DRUG

On the morning of Day 1: one 125 mg capsule PO 60 minutes prior to chemotherapy for participants 12 to 17 years of age

Also known as: MK-0869, Emend®

Aprepitant Regimen

Aprepitant 80 mg DRUG

On the morning of Days 2 and 3: one 80 mg capsule PO for participants 12 to 17 years of age

Also known as: MK-0869, Emend®

Aprepitant Regimen

Aprepitant powder for suspension (PFS) DRUG

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

Also known as: MK-0869, Emend®

Aprepitant Regimen

Ondansetron DRUG

Day 1: Administered according to product label for pediatric usage or local standard of care

Also known as: Zofran™

Aprepitant Regimen; Control Regimen

Placebo for Aprepitant 125 mg DRUG

On the morning of Day 1: one 125 mg capsule PO 60 minutes prior to chemotherapy for participants 12 to 17 years of age

Control Regimen

Placebo for Aprepitant 80 mg DRUG

On the morning of Days 2 and 3: one 80 mg capsule PO for participants 12 to 17 years of age

Control Regimen

Placebo for Aprepitant PFS DRUG

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

Control Regimen

Emetogenic chemotherapy DRUG

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."

Aprepitant Regimen; Control Regimen

Eligibility Criteria

• Age: 6 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• 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.

  PMID: 25770814 RESULT

• 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.

  PMID: 29893452 DERIVED

MeSH Terms

Conditions

Vomiting

Interventions

Aprepitant; Suspensions; Ondansetron

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations; Imidazoles; Azoles; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2011
• First Posted: May 30, 2011
• Study Start: September 13, 2011
• Primary Completion: March 14, 2013
• Study Completion: August 16, 2013
• Last Updated: September 25, 2018
• Results First Posted: April 4, 2014

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share