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

A Phase 4, Open-label, Single Arm Study to Evaluate the Safety and Tolerability of a Three-day Fosaprepitant Regimen Administered for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Pediatric Participants Receiving Emetogenic Chemotherapy

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.

Study Overview

• Status: Completed
• Conditions: Chemotherapy-induced Nausea and Vomiting
• Intervention / Treatment: Drug: Fosaprepitant Dimeglumine; Drug: 5-HT3 antagonist; Drug: Dexamethasone

Detailed Description

Upon completion of Cycle 1, participants were given the option to exit the study and be considered completed, or to continue on study therapy for up to 2 more (optional) 17-day cycles of chemotherapy where fosaprepitant was administered and additional safety data collected.

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 4

Contacts and Locations

Study Locations

• Greece
  • Thessaloniki, Greece, 546 36
    • University General Hospital of Thessaloniki "AHEPA" ( Site 0103)
  • Attiki
    • Athens, Attiki, Greece, 115 27
      • Athens Childrens Hospital Aglaia Kyriakou ( Site 0101)
    • Athens, Attiki, Greece, 115 27
      • University of Athens - Aghia Sophia Childrens Hospital ( Site 0102)
• Hungary
  • Budapest, Hungary, 1089
    • Heim Pal Orszagos Gyermekgyogyaszati Intezet ( Site 0202)
  • Borsod-Abauj-Zemplen
    • Miskolc, Borsod-Abauj-Zemplen, Hungary, 3526
      • Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi OktatoKorhaz ( Site 0203)
  • Csongrad
    • Szeged, Csongrad, Hungary, 6720
      • Szegedi Tudomanyegyetem - Szent-Gyorgyi Albert Klinikai Kozpont ( Site 0201)
• Lithuania
  • Kaunas, Lithuania, 50161
    • LSMUL Kauno Klinikos ( Site 0402)
  • Vilnius, Lithuania, 08406
    • Vaiku ligonine VsI VUL Santaros kliniku filialas ( Site 0401)
• Netherlands
  • Utrecht, Netherlands, 3584 CS
    • Prinses Maxima Centrum ( Site 0501)
• Peru
  • Lima, Peru, 15038
    • Instituto Nacional de Enfermedades Neoplasicas ( Site 1502)
  • Lima, Peru, 15073
    • Clinica Anglo Americana ( Site 1501)
  • Lima, Peru, 15074
    • Clinica Delgado ( Site 1503)
• Poland
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 01-211
      • Instytut Matki i Dziecka ( Site 0601)
    • Warszawa, Mazowieckie, Poland, 04-730
      • Instytut Pomnik Centrum Zdrowia Dziecka ( Site 0602)
• Russian Federation
  • Chelyabinskaya Oblast
    • Chelyabinsk, Chelyabinskaya Oblast, Russian Federation, 454076
      • Chelyabinsk Regional Children Clinical Hospital ( Site 0705)
  • Moskva
    • Moscow, Moskva, Russian Federation, 115478
      • Blokhin National Medical Oncology ( Site 0701)
    • Moscow, Moskva, Russian Federation, 117198
      • Dmitry Rogachev National Research Center ( Site 0704)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 197758
      • Clinical Research Center of specialized types medical care-Oncology ( Site 0706)
• United Kingdom
  • Leeds, United Kingdom, LS1 3EX
    • Leeds Teaching Hospitals NHS Trust ( Site 1002)
  • Liverpool, United Kingdom, L12 2AP
    • Alder Hey Childrens NHS Foundation Trust Hospital ( Site 1003)
  • Manchester, United Kingdom, M13 9WL
    • Royal Manchester Children's Hospital ( Site 1005)
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Childrens Hospital ( Site 1101)
  • California
    • Los Angeles, California, United States, 90027
      • Southern California Permanente Medical Group ( Site 1104)
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 1106)
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals and Clinics of Minnesota ( Site 1109)
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital ( Site 1111)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Fosaprepitant Treatment; 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; Participants received IV fosaprepitant dimeglumine ≤115 mg on Day 1 and ≤80 mg on Days 2 and 3 (dose adjusted for age).; Other Names: MK-0517; EMEND for injection®; Drug: 5-HT3 antagonist; 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.; Drug: Dexamethasone; Participants received optional oral dexamethasone at the investigator's discretion according to product label or standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2019
• Primary Completion (Actual): February 11, 2021
• Study Completion (Actual): February 11, 2021

Study Registration Dates

• First Submitted: August 9, 2019
• First Submitted That Met QC Criteria: August 9, 2019
• First Posted (Actual): August 13, 2019

Study Record Updates

• Last Update Posted (Actual): September 23, 2021
• Last Update Submitted That Met QC Criteria: September 22, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Serotonin Agents; Serotonin Antagonists; Neurokinin-1 Receptor Antagonists; Dexamethasone; Serotonin 5-HT3 Receptor Antagonists; Aprepitant; Fosaprepitant
• Other Study ID Numbers: 0517-045; 2018-004844-43 (EudraCT Number); MK-0517-045 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No