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

Phase 4
Completed
Conditions
Chemotherapy-induced Nausea and Vomiting
Interventions
Registration Number
NCT04054193
Lead Sponsor
Merck Sharp & Dohme LLC
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
103
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)
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Fosaprepitant TreatmentFosaprepitant DimeglumineParticipants 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.
Fosaprepitant Treatment5-HT3 antagonistParticipants 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.
Fosaprepitant TreatmentDexamethasoneParticipants 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.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants in Cycle 1 Who Experienced One or More Adverse Events (AEs)Up to 17 days

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.

Percentage of Participants in Cycle 1 Who Discontinued Study Drug Due to an Adverse Event (AE)Up to 3 days

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.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (26)

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

🇺🇸

Minneapolis, Minnesota, United States

Instituto Nacional de Enfermedades Neoplasicas ( Site 1502)

🇵🇪

Lima, Peru

Phoenix Childrens Hospital ( Site 1101)

🇺🇸

Phoenix, Arizona, United States

Heim Pal Orszagos Gyermekgyogyaszati Intezet ( Site 0202)

🇭🇺

Budapest, Hungary

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

🇭🇺

Miskolc, Borsod-Abauj-Zemplen, Hungary

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

🇭🇺

Szeged, Csongrad, Hungary

Clinica Anglo Americana ( Site 1501)

🇵🇪

Lima, Peru

Vaiku ligonine VsI VUL Santaros kliniku filialas ( Site 0401)

🇱🇹

Vilnius, Lithuania

Athens Childrens Hospital Aglaia Kyriakou ( Site 0101)

🇬🇷

Athens, Attiki, Greece

Dmitry Rogachev National Research Center ( Site 0704)

🇷🇺

Moscow, Moskva, Russian Federation

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

🇬🇷

Athens, Attiki, Greece

Instytut Matki i Dziecka ( Site 0601)

🇵🇱

Warszawa, Mazowieckie, Poland

Chelyabinsk Regional Children Clinical Hospital ( Site 0705)

🇷🇺

Chelyabinsk, Chelyabinskaya Oblast, Russian Federation

Blokhin National Medical Oncology ( Site 0701)

🇷🇺

Moscow, Moskva, Russian Federation

Southern California Permanente Medical Group ( Site 1104)

🇺🇸

Los Angeles, California, United States

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

🇺🇸

Chicago, Illinois, United States

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

🇺🇸

Memphis, Tennessee, United States

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

🇬🇷

Thessaloniki, Greece

LSMUL Kauno Klinikos ( Site 0402)

🇱🇹

Kaunas, Lithuania

Leeds Teaching Hospitals NHS Trust ( Site 1002)

🇬🇧

Leeds, United Kingdom

Clinica Delgado ( Site 1503)

🇵🇪

Lima, Peru

Prinses Maxima Centrum ( Site 0501)

🇳🇱

Utrecht, Netherlands

Alder Hey Childrens NHS Foundation Trust Hospital ( Site 1003)

🇬🇧

Liverpool, United Kingdom

Instytut Pomnik Centrum Zdrowia Dziecka ( Site 0602)

🇵🇱

Warszawa, Mazowieckie, Poland

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

🇷🇺

Saint Petersburg, Sankt-Peterburg, Russian Federation

Royal Manchester Children's Hospital ( Site 1005)

🇬🇧

Manchester, United Kingdom

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