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

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04054193
• Collaborator: (none)
• Enrollment: 103
• Locations: 26
• Arm: 1
• Actual Duration (Months): 17.1
• Patients Per Site: 4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chemotherapy-induced Nausea and Vomiting	Drug: Fosaprepitant Dimeglumine; Drug: 5-HT3 antagonist; Drug: Dexamethasone	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 103 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• 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
• Actual Study Start Date: Sep 9, 2019
• Actual Primary Completion Date: Feb 11, 2021
• Actual Study Completion Date: Feb 11, 2021

Arms and Interventions

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: EMEND for injection® MK-0517 ; 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.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 17, 2020

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT04054193
• Other Study ID Numbers: 0517-045; 2018-004844-43; MK-0517-045
• First Posted: Aug 13, 2019
• Last Update Posted: Sep 23, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Nausea; Vomiting; Dexamethasone; Fosaprepitant; Aprepitant; Serotonin 5-HT3 Receptor Antagonists

Study Results

Participant Flow

Recruitment Details	Eligible participants were recruited at 25 study sites in 9 countries.

Arm/Group Title	Fosaprepitant Treatment
Arm/Group Description	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-HT]) 3 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.
Period Title: Cycle 1
STARTED	103
Treated (≥1 Dose)	100
COMPLETED	98
NOT COMPLETED	5
Period Title: Cycle 1
STARTED	69
COMPLETED	48
NOT COMPLETED	21

Baseline Characteristics

Arm/Group Title	Fosaprepitant Treatment
Arm/Group Description	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-HT]) 3 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.
Overall Participants	103
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	7.7 (5.0)
Sex: Female, Male (Count of Participants)
Female	50 48.5%
Male	53 51.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	22 21.4%
Not Hispanic or Latino	77 74.8%
Unknown or Not Reported	4 3.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	14 13.6%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 1.9%
White	81 78.6%
More than one race	6 5.8%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants in Cycle 1 Who Experienced One or More Adverse Events (AEs)
Description	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.
Time Frame	Up to 17 days

Outcome Measure Data

Analysis Population Description

The analysis population consists of all allocated participants in Cycle 1 who received ≥1 dose of study intervention.

Arm/Group Title	Fosaprepitant Treatment
Arm/Group Description	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-HT]) 3 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.
Measure Participants	100
Number [Percentage of Participants]	80.0 77.7%

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis population consists of all allocated participants in Cycle 1 who received ≥1 dose of study intervention.

Arm/Group Title	Fosaprepitant Treatment
Arm/Group Description	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-HT]) 3 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.
Measure Participants	100
Number [Percentage of Participants]	2.0 1.9%

Adverse Events

Time Frame	Up to approximately 3.5 months
Adverse Event Reporting Description	All-cause mortality is reported for all allocated participants, and serious and nonserious adverse events are reported for all allocated participants who received ≥1 dose of study intervention. Findings from Cycle 1 and Cycles 2-3 are presented separately.
Arm/Group Title	Fosaprepitant Cycle 1		Fosaprepitant Cycles 2-3
Arm/Group Description	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-HT]) 3 receptor antagonist on Day 1 and optionally on Days 2-3 as background therapy.		Participants received fosaprepitant dimeglumine once daily (QD) for 3 days and were followed for 14 days during Cycles 2-3. Participants also optionally received dexamethasone as background therapy, and a 5-HT3 receptor antagonist on Day 1 and optionally on Days 2-3 as background therapy, of each 17-day cycle.
All Cause Mortality
	Fosaprepitant Cycle 1		Fosaprepitant Cycles 2-3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/103 (0%)		0/69 (0%)
Serious Adverse Events
	Fosaprepitant Cycle 1		Fosaprepitant Cycles 2-3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/100 (30%)		27/69 (39.1%)
Blood and lymphatic system disorders
Anaemia	1/100 (1%)	1	4/69 (5.8%)	5
Febrile neutropenia	17/100 (17%)	18	15/69 (21.7%)	20
Leukopenia	0/100 (0%)	0	2/69 (2.9%)	2
Lymphopenia	0/100 (0%)	0	1/69 (1.4%)	1
Myelosuppression	0/100 (0%)	0	1/69 (1.4%)	1
Neutropenia	0/100 (0%)	0	2/69 (2.9%)	2
Thrombocytopenia	0/100 (0%)	0	3/69 (4.3%)	3
Haematotoxicity	1/100 (1%)	1	1/69 (1.4%)	1
Pancytopenia	1/100 (1%)	1	1/69 (1.4%)	1
Gastrointestinal disorders
Nausea	2/100 (2%)	2	0/69 (0%)	0
Stomatitis	2/100 (2%)	2	2/69 (2.9%)	3
Vomiting	1/100 (1%)	1	1/69 (1.4%)	1
Abdominal pain	0/100 (0%)	0	1/69 (1.4%)	1
Colitis	0/100 (0%)	0	1/69 (1.4%)	1
General disorders
Fatigue	1/100 (1%)	1	1/69 (1.4%)	1
Pyrexia	1/100 (1%)	1	1/69 (1.4%)	1
Mucosal inflammation	0/100 (0%)	0	1/69 (1.4%)	1
Infections and infestations
Herpes zoster	1/100 (1%)	1	0/69 (0%)	0
Pharyngitis	1/100 (1%)	1	0/69 (0%)	0
Pneumocystis jirovecii pneumonia	1/100 (1%)	1	0/69 (0%)	0
Bacteraemia	0/100 (0%)	0	2/69 (2.9%)	2
Fungaemia	0/100 (0%)	0	1/69 (1.4%)	1
Upper respiratory tract infection	0/100 (0%)	0	1/69 (1.4%)	1
Injury, poisoning and procedural complications
Infusion related reaction	1/100 (1%)	1	0/69 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/100 (1%)	1	0/69 (0%)	0
Hypomagnesaemia	0/100 (0%)	0	1/69 (1.4%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/100 (1%)	1	0/69 (0%)	0
Nervous system disorders
Coordination abnormal	1/100 (1%)	1	0/69 (0%)	0
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome	0/100 (0%)	0	1/69 (1.4%)	1
Other (Not Including Serious) Adverse Events
	Fosaprepitant Cycle 1		Fosaprepitant Cycles 2-3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	64/100 (64%)		27/69 (39.1%)
Blood and lymphatic system disorders
Anaemia	24/100 (24%)	28	7/69 (10.1%)	8
Haematotoxicity	9/100 (9%)	9	10/69 (14.5%)	15
Neutropenia	15/100 (15%)	16	4/69 (5.8%)	4
Thrombocytopenia	11/100 (11%)	11	3/69 (4.3%)	3
Gastrointestinal disorders
Constipation	6/100 (6%)	6	3/69 (4.3%)	3
Nausea	24/100 (24%)	25	8/69 (11.6%)	9
Vomiting	16/100 (16%)	18	8/69 (11.6%)	13
Investigations
Neutrophil count decreased	14/100 (14%)	14	2/69 (2.9%)	2
Platelet count decreased	9/100 (9%)	9	4/69 (5.8%)	4
White blood cell count decreased	7/100 (7%)	8	1/69 (1.4%)	1
Metabolism and nutrition disorders
Decreased appetite	6/100 (6%)	6	0/69 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission.