Study of the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Fosaprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Children (MK-0517-029)

NCT ID: NCT01697579

Last Updated: 2019-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-13
• Study Completion Date: 2016-11-21

Brief Summary

The purpose of this study was to determine the appropriate dosing regimen of fosaprepitant, when administered with ondansetron (with or without dexamethasone), for the prevention of CINV in children from birth to <17 years of age. Fosaprepitant is a prodrug to aprepitant. All participants who completed the randomized Cycle 1 could elect to receive open-label fosaprepitant during optional Cycles 2-6.

Detailed Description

Under Amendment 01, 0517-029 enrolled participants in the following age cohorts: 2-<6, 6-<12 and 12-17 years old. The study was randomized, partially-blinded, with parallel group assignment. Participants were randomized to one of three fosaprepitant doses or the control group. (Amendment 02 and Amendment 03 were country-specific amendments in Brazil that were required as per local regulations with no change in study design.) Under Amendment 04, the 12-17 year-old cohort was closed since that cohort fully enrolled. An additional fosaprepitant dose was added and all participants were allocated to this one treatment group. Amendment 04 was open-label and enrolled participants in the following age cohorts: 0-<2, 2-<6 and 6-<12 years old.

Conditions

Chemotherapy-induced Nausea and Vomiting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Fosaprepitant 5 mg/kg-Cycle 1

Participants were administered intravenous (IV) fosaprepitant at the following weight-adjusted doses: participants 4 months to \<12 years old were administered 5 mg/kg (not to exceed 150 mg); participants 1 to \<4 months old were administered 2.5 mg/kg; participants 0 to \<1 month old were administered 1.25 mg/kg. Participants were also administered IV ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children \<6 months of age), with or without dexamethasone.

Group Type: EXPERIMENTAL

Fosaprepitant

Intervention Type: DRUG

Administered intravenously (IV) as a single dose

Ondansetron

Intervention Type: DRUG

Administered IV according to local labeling and/or local standard of care

Fosaprepitant 3 mg/kg-Cycle 1

Participants 12 to 17 years old were administered 150 mg IV fosaprepitant. Participants 2 to \<12 years old were administered a weight-adjusted dose of 3 mg/kg (not to exceed 150 mg). Participants were also administered IV ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children \<6 months of age), with or without dexamethasone.

Group Type: EXPERIMENTAL

Fosaprepitant

Intervention Type: DRUG

Administered intravenously (IV) as a single dose

Ondansetron

Intervention Type: DRUG

Administered IV according to local labeling and/or local standard of care

Fosaprepitant 1.2 mg/kg-Cycle 1

Participants 12 to 17 years old were administered 60 mg IV fosaprepitant. Participants 2 to \<12 years old were administered a weight-adjusted dose of 1.2 mg/kg (not to exceed 60 mg). Participants were also administered IV ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children \<6 months of age), with or without dexamethasone.

Group Type: EXPERIMENTAL

Fosaprepitant

Intervention Type: DRUG

Administered intravenously (IV) as a single dose

Ondansetron

Intervention Type: DRUG

Administered IV according to local labeling and/or local standard of care

Fosaprepitant 0.4 mg/kg-Cycle 1

Participants 12 to 17 years old were administered 20 mg IV fosaprepitant. Participants 2 to \<12 years old were administered a weight-adjusted dose of 0.4 mg/kg (not to exceed 20 mg). Participants were also administered IV ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children \<6 months of age), with or without dexamethasone.

Group Type: EXPERIMENTAL

Fosaprepitant

Intervention Type: DRUG

Administered intravenously (IV) as a single dose

Ondansetron

Intervention Type: DRUG

Administered IV according to local labeling and/or local standard of care

Placebo Control-Cycle 1

Participants were administered IV normal saline at volume to match age and weight specific doses of fosaprepitant. Participants were also administered IV ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children \<6 months of age), with or without dexamethasone.

Group Type: PLACEBO_COMPARATOR

Fosaprepitant Placebo

Intervention Type: DRUG

Administered IV as a single dose

Ondansetron

Intervention Type: DRUG

Administered IV according to local labeling and/or local standard of care

Fosaprepitant 5 mg/kg-Cycles 2-6

For optional Cycles 2-6, participants from the 5 mg/kg fosaprepitant arm in Cycle 1 were administered fosaprepitant 5 mg/kg IV (or age-adjusted equivalent). For Cycle 2, fosaprepitant was administered IV plus ondansetron with or without dexamethasone. For Cycles 3-6, fosaprepitant was administered IV plus a 5- hydroxytryptamine 3 (5-HT3) antagonist with or without dexamethasone. Participants 1 year or less were required to receive ondansetron in all cycles as the 5-HT3 antagonist.

Group Type: EXPERIMENTAL

Fosaprepitant

Intervention Type: DRUG

Administered intravenously (IV) as a single dose

5-hydroxytryptamine 3 antagonist

Intervention Type: DRUG

Administered IV according to local labeling and/or local standard of care

Fosaprepitant 3 mg/kg-Cycles 2-6

For optional Cycles 2-6, participants from Cycle 1 fosaprepitant arms (3, 1.2, or 0.4 mg/kg) or Cycle 1 control arm were administered fosaprepitant 3 mg/kg IV (or age-adjusted equivalent). For Cycle 2, fosaprepitant was administered IV plus ondansetron with or without dexamethasone. For Cycles 3-6, fosaprepitant was administered IV plus a 5-HT3 antagonist with or without dexamethasone.

Group Type: EXPERIMENTAL

Fosaprepitant

Intervention Type: DRUG

Administered intravenously (IV) as a single dose

5-hydroxytryptamine 3 antagonist

Intervention Type: DRUG

Administered IV according to local labeling and/or local standard of care

Interventions

Fosaprepitant

Administered intravenously (IV) as a single dose

Intervention Type: DRUG

Fosaprepitant Placebo

Administered IV as a single dose

Intervention Type: DRUG

Ondansetron

Administered IV according to local labeling and/or local standard of care

Intervention Type: DRUG

5-hydroxytryptamine 3 antagonist

Administered IV according to local labeling and/or local standard of care

Intervention Type: DRUG

Other Intervention Names

Fosaprepitant dimeglumine; MK-0517; EMEND® for Injection; Ondansetron hydrochloride; Zofran® Injection; 5-HT3

Eligibility Criteria

Inclusion Criteria

• Is 0 months (at least 37 weeks gestation) to <18 years of age
• Scheduled to receive chemotherapeutic agent(s) associated with moderate, high, or very high risk of emetogenicity for no more than 5 consecutive days for a documented malignancy, or a chemotherapy regimen not previously tolerated due to vomiting
• Expected to receive ondansetron as part of antiemetic regimen (Cycle 1); Expected to receive a 5-HT3 antagonist as part of antiemetic regimen (Cycles 2-6)
• If female and has begun menstruating, must have a negative pregnancy test prior to study participation and agree to remain abstinent or use a barrier form of contraception
• Predicted life expectancy of ≥3 months
• Pre-existing functioning central venous catheter
• Weight ≥3rd percentile for age and gender (and ≥3.0 kg)

Exclusion Criteria

• Vomited in the 24 hours prior study drug administration (Cycle 1)
• Current user of any illicit drugs (including marijuana) or current evidence of alcohol abuse
• Scheduled to receive stem cell rescue therapy in conjunction with study related course(s) of emetogenic chemotherapy
• Received or will receive radiation therapy to the abdomen or pelvis in the week prior to study drug administration and/or during the course of the study
• Pregnant or breast feeding
• Allergic to fosaprepitant, aprepitant, ondansetron, or any other 5-HT3 antagonist
• Has a symptomatic central nervous system (CNS) tumor causing nausea and/or vomiting
• Has an active infection, congestive heart failure, slow heart rate, or other uncontrolled disease other than cancer
• Mentally incapacitated or has a significant emotional or psychiatric disorder
• Known history of QT prolongation or is taking any medication known to lead to QT prolongation
• Taking other excluded medications
• Participated in any previous study of aprepitant or fosaprepitant, or taken an investigational drug within 4 weeks prior to study participation

• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Mora J, Valero M, DiCristina C, Jin M, Chain A, Bickham K. Pharmacokinetics/pharmacodynamics, safety, and tolerability of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in pediatric cancer patients. Pediatr Blood Cancer. 2019 Jun;66(6):e27690. doi: 10.1002/pbc.27690. Epub 2019 Mar 21.

Reference Type: RESULT

PMID: 30900392 (View on PubMed)

Other Identifiers

2012-002340-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-0517-029

Identifier Type: OTHER

Identifier Source: secondary_id

0517-029

Identifier Type: -

Identifier Source: org_study_id