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)

NCT ID: NCT01362530

Last Updated: 2018-09-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 307 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-13
• Study Completion Date: 2013-08-16

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Aprepitant Regimen

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.

Group Type: EXPERIMENTAL

Aprepitant 125 mg

Intervention Type: 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

Aprepitant 80 mg

Intervention Type: DRUG

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)

Intervention Type: 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

Ondansetron

Intervention Type: DRUG

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

Emetogenic chemotherapy

Intervention Type: 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."

Control Regimen

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.

Group Type: PLACEBO_COMPARATOR

Ondansetron

Intervention Type: DRUG

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

Placebo for Aprepitant 125 mg

Intervention Type: 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

Placebo for Aprepitant 80 mg

Intervention Type: DRUG

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

Intervention Type: 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

Emetogenic chemotherapy

Intervention Type: 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."

Interventions

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

Intervention Type: DRUG

Aprepitant 80 mg

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Ondansetron

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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."

Intervention Type: DRUG

Other Intervention Names

MK-0869, Emend®; MK-0869, Emend®; MK-0869, Emend®; Zofran™

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:

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: RESULT

PMID: 25770814 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29893452 (View on PubMed)

Study Documents

Document Type: CSR Synopsis

View Document

Other Identifiers

0869-208

Identifier Type: -

Identifier Source: org_study_id