Chemotherapy-induced Nausea and Vomiting
Conditions
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.
Interventions
Participants received IV fosaprepitant dimeglumine ≤115 mg on Day 1 and ≤80 mg on Days 2 and 3 (dose adjusted for age).
DRUG5-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.
DRUGDexamethasone
Participants received optional oral dexamethasone at the investigator's discretion according to product label or standard of care.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 17 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Greece, Hungary, Lithuania, Netherlands, Peru, Poland, Russia, United Kingdom, United States
Participant flow
Recruitment details
Eligible participants were recruited at 25 study sites in 9 countries.
Participants by arm
| Arm | Count |
|---|---|
| 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 \[5-HT\]) 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. | 103 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Cycle 1 | Allocated but not treated | 3 |
| Cycle 1 | Consent withdrawn by parent/guardian | 1 |
| Cycle 1 | Physician Decision | 1 |
| Cycles 2-3 | Consent withdrawn by parent/guardian | 2 |
| Cycles 2-3 | Physician Decision | 2 |
| Cycles 2-3 | Various reasons | 17 |
Baseline characteristics
| Characteristic | Fosaprepitant Treatment |
|---|---|
| Age, Continuous | 7.7 Years STANDARD_DEVIATION 5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 77 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 14 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 81 Participants |
| Sex: Female, Male Female | 50 Participants |
| Sex: Female, Male Male | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 103 | 0 / 69 |
| other Total, other adverse events | 64 / 100 | 27 / 69 |
| serious Total, serious adverse events | 30 / 100 | 27 / 69 |
Outcome results
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.
Time frame: Up to 3 days
Population: The analysis population consists of all allocated participants in Cycle 1 who received ≥1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fosaprepitant Treatment | Percentage of Participants in Cycle 1 Who Discontinued Study Drug Due to an Adverse Event (AE) | 2.0 Percentage of Participants |
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.
Time frame: Up to 17 days
Population: The analysis population consists of all allocated participants in Cycle 1 who received ≥1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fosaprepitant Treatment | Percentage of Participants in Cycle 1 Who Experienced One or More Adverse Events (AEs) | 80.0 Percentage of Participants |