Safety of a Three-Day Fosaprepitant Regimen for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Pediatric Participants (MK-0517-045)

NCT04054193 | Completed Phase 4 Results FDA Drug

• 3 other identifiers: 0517-045MK-0517-0452018-004844-43
• Study Type: interventional
• Target: 103
• Locations: 9 countries
• Sites: 26

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of a 3-day intravenous (IV) fosaprepitant dimeglumine (MK-0517) regimen for the prevention of CINV in pediatric participants scheduled to receive emetogenic chemotherapy. Each participant was enrolled in Cycle 1 (on which the primary study objectives were based), consisting of the 3-day treatment cycle and 14 days of follow-up for a total of 17 days.

Conditions

Chemotherapy-induced Nausea and Vomiting

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants in Cycle 1 Who Experienced One or More Adverse Events (AEs)

  An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. The percentage of participants in Cycle 1 who experience one or more AE(s) is presented.

  Up to 17 days

• Percentage of Participants in Cycle 1 Who Discontinued Study Drug Due to an Adverse Event (AE)

  An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. The percentage of participants in Cycle 1 who discontinue study treatment due to an AE is presented.

  Up to 3 days

Study Arms (1)

Fosaprepitant Treatment

EXPERIMENTAL

Participants received fosaprepitant dimeglumine once daily (QD) for 3 days and were followed for 14 days during the 17-day Cycle 1. Participants also optionally received dexamethasone as background therapy, and a serotonin (5-hydroxytryptamine \[5-HT3\]) receptor antagonist on Day 1 and optionally on Days 2-3 as background therapy. After completing Cycle 1, participants had the option to continue for up to 2 additional 17-day cycles of the same treatment regimen.

Drug: Fosaprepitant Dimeglumine; Drug: 5-HT3 antagonist; Drug: Dexamethasone

Interventions

Fosaprepitant Dimeglumine DRUG

Participants received IV fosaprepitant dimeglumine ≤115 mg on Day 1 and ≤80 mg on Days 2 and 3 (dose adjusted for age).

Also known as: EMEND for injection®, MK-0517

Fosaprepitant Treatment

5-HT3 antagonist DRUG

All participants received an oral 5-hydroxytryptamine (serotonin; \[5-HT\]) 3 receptor antagonist on Day 1 and had the option to take on Days 2-3. The dose was as per product label or standard of care.

Fosaprepitant Treatment

Dexamethasone DRUG

Participants received optional oral dexamethasone at the investigator's discretion according to product label or standard of care.

Fosaprepitant Treatment

Eligibility Criteria

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

You may qualify if:

• Is receiving a moderately or highly emetogenic chemotherapy agent/regimen or a chemotherapy agent/regimen not previously tolerated due to vomiting
• Has a Lansky Play Performance score ≥60 (participants ≤16 years of age) or a Karnofsky score ≥60 (participants \>16 years of age)
• Has a pre-existing functional central venous catheter available for study treatment administration
• Is fosaprepitant naïve
• Has a predicted life expectancy ≥3 months
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP) OR is a WOCBP and agrees to not be sexually active or use a highly effective contraceptive method for at least 28 days prior to receiving study treatment, during the treatment period, and for at least 30 days (or local standard of care if longer) after the last dose of study treatment (including the optional cycles)
• Has a negative highly sensitive pregnancy test (urine or serum as required by local regulations) prior to the start of fosaprepitant administration in a given cycle if a WOCBP
• Weighs at least 6 kilograms (kg)

You may not qualify if:

• Will receive stem cell rescue therapy in conjunction with a study-related course of emetogenic chemotherapy or during the 14 days following administration of fosaprepitant
• Is currently a user of any recreational or illicit drugs or has current evidence of drug or alcohol abuse or dependence as determined by the investigator
• Is mentally incapacitated or has a significant emotional or psychiatric disorder that, in the opinion of the investigator, precludes study entry
• Is pregnant or breast feeding
• Is allergic to fosaprepitant, aprepitant, or prescribed 5-HT3 antagonist
• Has an active infection (eg, pneumonia), congestive heart failure, bradyarrhythmia, any uncontrolled disease (eg, diabetic ketoacidosis, gastrointestinal obstruction) except for malignancy, or has any illness which in the opinion of the investigator, might confound the results of the study or pose unwarranted risk in administering study treatment or concomitant therapy to the participant
• Is a WOCBP who has a positive pregnancy test at screening (Cycle 1) or on Day 1 of optional Cycles 2 or 3
• Has been started on systemic corticosteroid therapy within 72 hours prior to study treatment administration or is expected to receive a corticosteroid as part of the chemotherapy regimen. Exceptions apply
• Is taking excluded medications
• Has ever participated in a previous study of aprepitant or fosaprepitant or has taken a non-approved (investigational) drug within the last 4 weeks
• Has a known history of QT prolongation or is taking any medication that is known to lead to QT prolongation

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (26)

Phoenix Childrens Hospital ( Site 1101)

Phoenix, Arizona, 85016, United States

Location

Southern California Permanente Medical Group ( Site 1104)

Los Angeles, California, 90027, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 1106)

Chicago, Illinois, 60611, United States

Location

Children's Hospitals and Clinics of Minnesota ( Site 1109)

Minneapolis, Minnesota, 55404, United States

Location

St. Jude Children's Research Hospital ( Site 1111)

Memphis, Tennessee, 38105, United States

Location

Athens Childrens Hospital Aglaia Kyriakou ( Site 0101)

Athens, Attica, 115 27, Greece

Location

University of Athens - Aghia Sophia Childrens Hospital ( Site 0102)

Athens, Attica, 115 27, Greece

Location

University General Hospital of Thessaloniki "AHEPA" ( Site 0103)

Thessaloniki, 546 36, Greece

Location

Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi OktatoKorhaz ( Site 0203)

Miskolc, Borsod-Abauj Zemplen county, 3526, Hungary

Location

Szegedi Tudomanyegyetem - Szent-Gyorgyi Albert Klinikai Kozpont ( Site 0201)

Szeged, Csongrád megye, 6720, Hungary

Location

Heim Pal Orszagos Gyermekgyogyaszati Intezet ( Site 0202)

Budapest, 1089, Hungary

Location

LSMUL Kauno Klinikos ( Site 0402)

Kaunas, 50161, Lithuania

Location

Vaiku ligonine VsI VUL Santaros kliniku filialas ( Site 0401)

Vilnius, 08406, Lithuania

Location

Prinses Maxima Centrum ( Site 0501)

Utrecht, 3584 CS, Netherlands

Location

Instituto Nacional de Enfermedades Neoplasicas ( Site 1502)

Lima, 15038, Peru

Location

Clinica Anglo Americana ( Site 1501)

Lima, 15073, Peru

Location

Clinica Delgado ( Site 1503)

Lima, 15074, Peru

Location

Instytut Matki i Dziecka ( Site 0601)

Warsaw, Masovian Voivodeship, 01-211, Poland

Location

Instytut Pomnik Centrum Zdrowia Dziecka ( Site 0602)

Warsaw, Masovian Voivodeship, 04-730, Poland

Location

Chelyabinsk Regional Children Clinical Hospital ( Site 0705)

Chelyabinsk, Chelyabinsk Oblast, 454076, Russia

Location

Blokhin National Medical Oncology ( Site 0701)

Moscow, Moscow, 115478, Russia

Location

Dmitry Rogachev National Research Center ( Site 0704)

Moscow, Moscow, 117198, Russia

Location

Clinical Research Center of specialized types medical care-Oncology ( Site 0706)

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

Leeds Teaching Hospitals NHS Trust ( Site 1002)

Leeds, LS1 3EX, United Kingdom

Location

Alder Hey Childrens NHS Foundation Trust Hospital ( Site 1003)

Liverpool, L12 2AP, United Kingdom

Location

Royal Manchester Children's Hospital ( Site 1005)

Manchester, M13 9WL, United Kingdom

Location

Related Publications (1)

• Garcia Leon JL, DiCristina C, Yao R, Afzal AS. Safety and Tolerability of a 3-Day Fosaprepitant Regimen for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Pediatric Patients: Results of an Open-Label, Single-Arm Phase 4 Trial. Pediatr Hematol Oncol. 2025 Mar;42(2):79-91. doi: 10.1080/08880018.2024.2437047. Epub 2024 Dec 10.

  PMID: 39655741 RESULT

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Vomiting

Interventions

fosaprepitant; Aprepitant; Serotonin 5-HT3 Receptor Antagonists; Dexamethasone

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; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

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 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2019
• First Posted: August 13, 2019
• Study Start: September 9, 2019
• Primary Completion: February 11, 2021
• Study Completion: February 11, 2021
• Last Updated: January 16, 2025
• Results First Posted: September 23, 2021

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

LI (2); US (5); HU (3); PL (2); RU (4); GB (3); GR (3); PE (3); NL (1)