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

Chemotherapy-induced Nausea and Vomiting Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04054193
• Other study ID #: 0517-045
• Secondary ID: 2018-004844-43MK
• Status: Completed
• Phase: Phase 4
• Start date: September 9, 2019
• Est. completion date: February 11, 2021

Study information

• Verified date: September 2021
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: February 11, 2021
• Est. primary completion date: February 11, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Chemotherapy-induced Nausea and Vomiting
• Nausea
• Vomiting

Intervention

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

Locations

Country	Name	City	State
Greece	Athens Childrens Hospital Aglaia Kyriakou ( Site 0101)	Athens	Attiki
Greece	University of Athens - Aghia Sophia Childrens Hospital ( Site 0102)	Athens	Attiki
Greece	University General Hospital of Thessaloniki "AHEPA" ( Site 0103)	Thessaloniki
Hungary	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
Lithuania	LSMUL Kauno Klinikos ( Site 0402)	Kaunas
Lithuania	Vaiku ligonine VsI VUL Santaros kliniku filialas ( Site 0401)	Vilnius
Netherlands	Prinses Maxima Centrum ( Site 0501)	Utrecht
Peru	Clinica Anglo Americana ( Site 1501)	Lima
Peru	Clinica Delgado ( Site 1503)	Lima
Peru	Instituto Nacional de Enfermedades Neoplasicas ( Site 1502)	Lima
Poland	Instytut Matki i Dziecka ( Site 0601)	Warszawa	Mazowieckie
Poland	Instytut Pomnik Centrum Zdrowia Dziecka ( Site 0602)	Warszawa	Mazowieckie
Russian Federation	Chelyabinsk Regional Children Clinical Hospital ( Site 0705)	Chelyabinsk	Chelyabinskaya Oblast
Russian Federation	Blokhin National Medical Oncology ( Site 0701)	Moscow	Moskva
Russian Federation	Dmitry Rogachev National Research Center ( Site 0704)	Moscow	Moskva
Russian Federation	Clinical Research Center of specialized types medical care-Oncology ( Site 0706)	Saint Petersburg	Sankt-Peterburg
United Kingdom	Leeds Teaching Hospitals NHS Trust ( Site 1002)	Leeds
United Kingdom	Alder Hey Childrens NHS Foundation Trust Hospital ( Site 1003)	Liverpool
United Kingdom	Royal Manchester Children's Hospital ( Site 1005)	Manchester
United States	Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 1106)	Chicago	Illinois
United States	Southern California Permanente Medical Group ( Site 1104)	Los Angeles	California
United States	St. Jude Children's Research Hospital ( Site 1111)	Memphis	Tennessee
United States	Children's Hospitals and Clinics of Minnesota ( Site 1109)	Minneapolis	Minnesota
United States	Phoenix Childrens Hospital ( Site 1101)	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

United States,  Greece,  Hungary,  Lithuania,  Netherlands,  Peru,  Poland,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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