Clinical trial NCT02519842: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Chemotherapy-induced Nausea and Vomiting
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-08-11
Enrollment: 75
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Experienced a Complete Response During the Delayed Phase (>24 to 120 Hours Post Initiation of Chemotherapy) in Cycle 1
timeFrame: >24 to 120 hours post initiation of chemotherapy (1 to 15 days after the dose of study drug)
measure: Percentage of Participants Who Experienced One or More Adverse Events
timeFrame: Up to 6.5 months (up to 2 weeks after last dose of study drug)
measure: Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event
timeFrame: Up to 6 months (up to last dose of study drug)
Secondary outcomes:
measure: Percentage of Participants Who Experienced a Complete Response During the Acute Phase (0 to 24 Hours Post Initiation of Chemotherapy) in Cycle 1
timeFrame: 0 to 24 hours post initiation of chemotherapy (up to 1 day after the dose of study drug)
measure: Percentage of Participants Who Experienced a Complete Response During the Overall Phase (0 to 120 Hours Post Initiation of Chemotherapy) in Cycle 1
timeFrame: 0 to 120 hours post initiation of chemotherapy (up to 15 days after the dose of study drug)
measure: 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
timeFrame: 0 to 120 hours post initiation of chemotherapy (up to 15 days after the dose of study drug)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: