Clinical trial NCT04054193: Safety of a Three-Day Fosaprepitant Regimen for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Pediatric Participants (MK-0517-045)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chemotherapy-induced Nausea and Vomiting
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2019-08-13
Enrollment: 103
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants in Cycle 1 Who Experienced One or More Adverse Events (AEs)
timeFrame: Up to 17 days
measure: Percentage of Participants in Cycle 1 Who Discontinued Study Drug Due to an Adverse Event (AE)
timeFrame: Up to 3 days
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital ( Site 1101)
state: Arizona
city: Los Angeles
country: United States
facility: Southern California Permanente Medical Group ( Site 1104)
state: California
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 1106)
state: Illinois
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota ( Site 1109)
state: Minnesota
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital ( Site 1111)
state: Tennessee
city: Athens
country: Greece
facility: Athens Childrens Hospital Aglaia Kyriakou ( Site 0101)
state: Attiki
city: Athens
country: Greece
facility: University of Athens - Aghia Sophia Childrens Hospital ( Site 0102)
state: Attiki
city: Thessaloniki
country: Greece
facility: University General Hospital of Thessaloniki "AHEPA" ( Site 0103)
city: Miskolc
country: Hungary
facility: Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi OktatoKorhaz ( Site 0203)
state: Borsod-Abauj-Zemplen
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem - Szent-Gyorgyi Albert Klinikai Kozpont ( Site 0201)
state: Csongrad
city: Budapest
country: Hungary
facility: Heim Pal Orszagos Gyermekgyogyaszati Intezet ( Site 0202)
city: Kaunas
country: Lithuania
facility: LSMUL Kauno Klinikos ( Site 0402)
city: Vilnius
country: Lithuania
facility: Vaiku ligonine VsI VUL Santaros kliniku filialas ( Site 0401)
city: Utrecht
country: Netherlands
facility: Prinses Maxima Centrum ( Site 0501)
city: Lima
country: Peru
facility: Instituto Nacional de Enfermedades Neoplasicas ( Site 1502)
city: Lima
country: Peru
facility: Clinica Anglo Americana ( Site 1501)
city: Lima
country: Peru
facility: Clinica Delgado ( Site 1503)
city: Warszawa
country: Poland
facility: Instytut Matki i Dziecka ( Site 0601)
state: Mazowieckie
city: Warszawa
country: Poland
facility: Instytut Pomnik Centrum Zdrowia Dziecka ( Site 0602)
state: Mazowieckie
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Children Clinical Hospital ( Site 0705)
state: Chelyabinskaya Oblast
city: Moscow
country: Russian Federation
facility: Blokhin National Medical Oncology ( Site 0701)
state: Moskva
city: Moscow
country: Russian Federation
facility: Dmitry Rogachev National Research Center ( Site 0704)
state: Moskva
city: Saint Petersburg
country: Russian Federation
facility: Clinical Research Center of specialized types medical care-Oncology ( Site 0706)
state: Sankt-Peterburg
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust ( Site 1002)
city: Liverpool
country: United Kingdom
facility: Alder Hey Childrens NHS Foundation Trust Hospital ( Site 1003)
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital ( Site 1005)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.