Efficacy and Safety Study of Fosaprepitant (MK-0517) Plus Ondansetron Versus Ondansetron Alone for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Pediatric Participants (MK-0517-044)

February 28, 2019 updated by: Merck Sharp & Dohme LLC

A Phase III, Randomized, Placebo-Controlled Clinical Trial to Study the Efficacy and Safety of MK-0517/Fosaprepitant and Ondansetron Versus Ondansetron for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Pediatric Subjects Receiving Emetogenic Chemotherapy

The purpose of this study is to evaluate the efficacy and safety of fosaprepitant (MK-0517) plus ondansetron versus ondansetron alone for the prevention of chemotherapy-induced nausea and vomiting (CINV) in pediatric participants scheduled to receive chemotherapeutic agent(s) associated with moderate or high risk of causing emesis (vomiting), or chemotherapy agent(s) not previously tolerated due to vomiting. The primary hypothesis is that a single dose of fosaprepitant in combination with ondansetron provides superior control of CINV compared to ondansetron alone as measured by the percentage of participants with a Complete Response (no vomiting, no retching, and no use of rescue medications) in the delayed phase (>24 to 120 hours) following initiation of emetogneic chemotherapy in Cycle 1.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

In Cycle 1, participants will receive double-blind study drug (fosaprepitant plus ondansetron with or without dexamethasone OR placebo to fosaprepitant plus ondansetron with or without dexamethasone). Upon completion of Cycle 1, participants may have the option to continue for up to 5 additional open-label cycles, receiving fosaprepitant plus ondansetron with or without dexamethasone.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
75

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Is 0 (at least 37 weeks gestation) to 17 years of age at time of randomization
  • Has a Lansky Play Performance score ≥60 (participants ≤16 years of age) or a Karnofsky score ≥60 (participants >16 years of age)
  • Has a predicted life expectancy ≥3 months
  • Is receiving chemotherapeutic agent(s) associated with moderate or high risk of emetogenicity, or a chemotherapy regimen not previously tolerated due to vomiting
  • Has a preexisting functional central venous catheter available for study drug administration
  • Is male OR is female who is not of reproductive potential OR is female who is of reproductive potential and agrees to avoid becoming pregnant in the 28 days prior to receiving study drug, while receiving study drug and for at least 30 days after last dose of study drug

Exclusion Criteria:

  • Has vomited in the 24 hours prior to chemotherapy initiation on Treatment Day 1
  • Has a symptomatic primary or metastatic central nervous system (CNS) malignancy with nausea and/or vomiting (asymptomatic participants may participate in study)
  • Will be receiving stem cell rescue therapy in conjunction with study-related course of emetogenic chemotherapy or during the 14 days following administration of fosaprepitant/placebo for fosaprepitant
  • Has received or will receive total body irradiation of radiation therapy to the abdomen or pelvis in the week prior to Treatment Day 1 and/or during the diary reporting period (120 hours following initiation of chemotherapy)
  • Has had benzodiazepine, opioid or opioid like therapy initiated within 48 hours prior to study drug administration, or is expected to receive within 120 hours following initiation of chemotherapy except for single doses of midazolam, temazepam or triazolam
  • Has started on systemic corticosteroid therapy within 72 hours prior to study drug administration or is expected to receive a corticosteroid as part of the chemotherapy regimen
  • Is currently taking, or has taken within 48 hours of Treatment Day 1 the following drugs with antiemetic properties: 5-hydroxytryptamine 3 (5-HT3) antagonists (e.g., ondansetron), benzamides (e.g., haloperidol), cyclizine, domperidone, herbal therapies with potential antiemetic properties, olanzapine, phenothiazines (e.g., prochlorpenzine), scopolamine (this is not an exhaustive list)
  • Is or has an immediate family member who is investigational site or sponsor staff directly involved with this study
  • Is currently a user of any recreational or illicit drugs (including marijuana) or has current evidence of drug or alcohol abuse or dependence
  • Is mentally incapacitated or has a significant emotional or psychiatric disorder
  • Is pregnant or breast feeding
  • Is allergic to fosaprepitant, aprepitant (MK-0869), ondansetron, or any other 5-HT3 antagonist
  • Has a known history of QT prolongation or is taking any medication that is known to lead to QT prolongation
  • Has an active infection (e.g., pneumonia), congestive heart failure, bradyarrhythmia, any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction) except for malignancy
  • Has ever participated in a previous study of aprepitant or fosaprepitant or has taken an investigational drug with the last 4 weeks.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Fosaprepitant Regimen Cycle 1
Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.
Drug: Dexamethasone
Drug: Ondansetron
Other Names:
  • Zofran®
Drug: Fosaprepitant
Other Names:
  • EMEND for injection®
Placebo Comparator: Control Regimen Cycle 1
Participants received a single dose of matched placebo for fosaprepitant IV on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.
Drug: Dexamethasone
Drug: Ondansetron
Other Names:
  • Zofran®
Drug: Placebo for fosaprepitant
Experimental: Fosaprepitant Regimen Cycles 2-6
Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) IV on Day 1 prior to chemotherapy plus a 5-hydroxytryptamine 3 (5-HT3) antagonist on Day 1 prior to chemotherapy and per product label or standard of care. Participants may also have received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.
Drug: Dexamethasone
Drug: Fosaprepitant
Other Names:
  • EMEND for injection®
Drug: 5-HT3 antagonist

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Experienced a Complete Response During the Delayed Phase (>24 to 120 Hours Post Initiation of Chemotherapy) in Cycle 1
Time Frame: >24 to 120 hours post initiation of chemotherapy (1 to 15 days after the dose of study drug)
Complete Response was defined as no vomiting, no retching, and no use of rescue medication following the initiation of emetogenic chemotherapy in Cycle 1. A vomiting episode was specified as one or more episodes of emesis (expulsion of stomach contents through the mouth) or retching/dry heaves (an attempt to vomit that is not productive of stomach contents). Distinct vomiting episodes were separated by the absence of emesis and retching for at least one minute. The date and time of each vomiting episode was recorded by participants in diaries at the time of occurrence. The percentage of participants with no vomiting and no retching episodes in the delayed phase, defined as the time period of >24 to120 hours post initiation of chemotherapy in Cycle 1, was calculated.
>24 to 120 hours post initiation of chemotherapy (1 to 15 days after the dose of study drug)
Percentage of Participants Who Experienced One or More Adverse Events
Time Frame: Up to 6.5 months (up to 2 weeks after last dose of study drug)
An adverse event (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. A statistical analysis was performed for Tier 2 AEs in Cycle 1 to compare the percentage of participants who received fosaprepitant regimen and experienced at least 1 Tier 2 AE compared with the percentage of participants in the control regimen. The Tier 2 endpoint included broad clinical and laboratory AE categories consisting of the percentage of participants with any AE, drug-related AE, serious AE, and AEs that are both drug-related and serious. Tier 2 AEs were not pre-specified as events of interest and inclusion in the Tier 2 analysis required that at least 4 participants in any treatment group exhibited the AE.
Up to 6.5 months (up to 2 weeks after last dose of study drug)
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event
Time Frame: Up to 6 months (up to last dose of study drug)
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. A statistical analysis was performed to compare the percentage of participants who discontinued in Cycle 1 due to an AE and received fosaprepitant regimen compared with the percentage of participants who received control regimen.
Up to 6 months (up to last dose of study drug)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Experienced a Complete Response During the Acute Phase (0 to 24 Hours Post Initiation of Chemotherapy) in Cycle 1
Time Frame: 0 to 24 hours post initiation of chemotherapy (up to 1 day after the dose of study drug)
Complete Response was defined as no vomiting, no retching, and no use of rescue medication following the initiation of emetogenic chemotherapy in Cycle 1. A vomiting episode was specified as one or more episodes of emesis (expulsion of stomach contents through the mouth) or retching/dry heaves (an attempt to vomit that is not productive of stomach contents). Distinct vomiting episodes were separated by the absence of emesis and retching for at least one minute. The date and time of each vomiting episode was recorded by participants in diaries at the time of occurrence. The percentage of participants with no vomiting and no retching episodes in the acute phase, defined as the time period of 0 to 24 hours post initiation of chemotherapy in Cycle 1, was calculated.
0 to 24 hours post initiation of chemotherapy (up to 1 day after the dose of study drug)
Percentage of Participants Who Experienced a Complete Response During the Overall Phase (0 to 120 Hours Post Initiation of Chemotherapy) in Cycle 1
Time Frame: 0 to 120 hours post initiation of chemotherapy (up to 15 days after the dose of study drug)
Complete Response was defined as no vomiting, no retching, and no use of rescue medication following the initiation of emetogenic chemotherapy in Cycle 1. A vomiting episode was specified as one or more episodes of emesis (expulsion of stomach contents through the mouth) or retching/dry heaves (an attempt to vomit that is not productive of stomach contents). Distinct vomiting episodes were separated by the absence of emesis and retching for at least one minute. The date and time of each vomiting episode was recorded by participants in diaries at the time of occurrence. The percentage of participants with no vomiting and no retching episodes in the overall phase, defined as the time period of 0 to 120 hours post initiation of chemotherapy in Cycle 1, was calculated.
0 to 120 hours post initiation of chemotherapy (up to 15 days after the dose of study drug)
Percentage of Participants Who Experienced No Vomiting, Regardless of Rescue Medication Use, During the Overall Phase (0 to 120 Hours Post Initiation of Chemotherapy) in Cycle 1
Time Frame: 0 to 120 hours post initiation of chemotherapy (up to 15 days after the dose of study drug)
Vomiting was assessed, regardless of rescue medicine use, following the initiation of emetogenic chemotherapy in Cycle 1. A vomiting episode was specified as one or more episodes of emesis (expulsion of stomach contents through the mouth) or retching/dry heaves (an attempt to vomit that is not productive of stomach contents). Distinct vomiting episodes were separated by the absence of emesis and retching for at least one minute. The date and time of each vomiting episode was recorded by participants in diaries at the time of occurrence. Rescue medication was permitted to alleviate symptoms of established nausea or vomiting; but not as preventive medication. The percentage of participants with no vomiting and no retching episodes in the overall phase, defined as the time period of 0 to 120 hours post initiation of chemotherapy in Cycle 1, was calculated.
0 to 120 hours post initiation of chemotherapy (up to 15 days after the dose of study drug)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Merck Sharp & Dohme LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 14, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 24, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 24, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 7, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 7, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 11, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 15, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 28, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0517-044
  • 2014-001783-34 (EudraCT Number)
  • MK-0517-044 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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