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

In order to be eligible for participation in this trial, the subject must, for cycle 1:;1.have parent/legal guardian (legally authorized representative) agreement to the subject*s participation as indicated by parent/legal guardian signature on the informed consent form. Subject 12 to 17 years of age, or as required by local regulation, assents and has the ability to understand the nature and intent of the study including the ability to comply with study procedures, complete study diary, and is willing to keep scheduled study visits. ;2.be 0 (at least 37 weeks gestation) to 17 years of age at time of randomization.;3.have a Lansky Play Performance score >=60 (subjects <=16 years of age) or a Karnofsky score >=60 (subjects >16 years of age) as defined in Section 12.4 -Lansky and Karnofsky Performance Status Scales.;4.have a predicted life expectancy >=3 months.;5.be receiving chemotherapeutic agent(s) associated with moderate or high risk of emetogenicity for a documented malignancy, or a chemotherapy regimen not previously tolerated due to vomiting. ;Cycle 1 only: If a subject*s chemotherapy regimen has multiple chemotherapies with different emetogenic potential, then the most emetogenic agent must be part of the Day 1 regimen. ;6.have a preexisting functional central venous catheter available for study drug administration.;7.Meet one of the following:;If the subject is a female who is of reproductive potential, the subject must: have a negative urine pregnancy test prior to fosaprepitant dosing in a cycle; must agree to avoid becoming pregnant in the 28 days prior to receiving study drug, while receiving study drug and for at least 30 days (or local standard of care if longer) after the last dose of study drug (including the optional cycles) by complying with one of the following: (1) practice abstinence from heterosexual activity OR (2) use (or have her partner use) acceptable contraception during heterosexual activity.;The subject is a male.;The subject is a female who is not of reproductive potential, defined as a female who either: (1) has not begun menses; (2) has had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion at least 6 weeks prior to screening; OR (3) has a congenital or acquired condition that prevents childbearing.;In order to be eligible for participation in an optional cycle, subject must meet inclusion criteria 5, 6 and 7 above in addition to the following:;8.have completed the preceding study cycle and related study procedures satisfactorily, have no unresolved drug related adverse events and continued participation in an optional cycle poses no unwarranted risk to the subject as determined by the investigator. ;9.have parent/legal guardian (legally authorized representative) or subject (if subject is 18 years old) agreement to the subject*s participation as indicated by parent/legal guardian or subject (if subject is 18 years old) signature on the informed consent form for the optional cycles. Subject 12 to 17 years of age, or as required by local regulation, assents and has the ability to understand the nature and intent of the study including the ability to comply with study procedures and is willing to keep scheduled study visits.;Refer to Protocol for complete list

The subject must be excluded from participating in the trial if:;Exclusion criteria for Cycle 1 only:;1.has vomited in the 24 hours prior to chemotherapy initiation on Treatment Day 1.;2.has a symptomatic primary or metastatic central nervous system (CNS) malignancy with nausea and/or vomiting. Subject who is asymptomatic is allowed to participate.;3.has abnormal laboratory values as follows:;•peripheral absolute neutrophil count (ANC) <1000/mm3;•platelet count < 75,000/mm3;•aspartate aminotransferase (AST) > 5.0 x upper limit of normal (ULN) for age;•alanine aminotransferase (ALT) > 5.0 x ULN for age;•bilirubin > 1.5 x ULN for age;•creatinine > 1.5 x ULN for age;4.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. ;5.has received or will receive total body irradiation or radiation therapy to the abdomen (includes the level of the diaphragm and below) or pelvis in the week prior to Treatment Day 1 and/or during the diary reporting period (120 hours following initiation of chemotherapy).;6.has had benzodiazepine (potential to alleviate nausea and vomiting), opioid or opioid like (e.g., tramadol hydrochloride) therapy (potential to enhance nausea and vomiting) initiated within 48 hours prior to study drug administration, or is expected to receive within 120 hours following initiation of chemotherapy, except for single daily doses of midazolam, temazepam or triazolam. Continuation of chronic benzodiazepine, opioid or opioid like therapy is permitted provided it was initiated at least 48 hours prior to study drug administration.;7.has been 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.;Exceptions:;subject who is receiving chronic (>72 hours), daily steroid therapy can be enrolled provided the steroid dose is not >0.14 mg/kg (up to 10 mg) of prednisone daily or equivalent.;for supportive care, subject is permitted to receive a single dose of corticosteroid within 3 days prior (but not on the day of study drug administration) provided it is less than the equivalent of 20 mg of prednisone.;8.is currently taking, or has taken within 48 hours of Treatment Day 1 the following drugs with antiemetic properties: 5-HT3 antagonists (e.g., ondansetron), benzamides (e.g., metoclopramide), butyrophenones (e.g., haloperidol), cyclizine, domperidone, herbal therapies with potential antiemetic properties, olanzapine, phenothiazines (e.g., prochlorpenzine), scopolamine. ;Exclusion criteria for Cycle 1 and optional Cycles 2 to 6:;9.is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial. ;10.is currently a user of any recreational or illicit drugs (including marijuana) or has current evidence of drug or alcohol abuse or dependence as determined by the investigator.;11.is mentally incapacitated or has a significant emotional or psychiatric disorder that, in the opinion of the investigator, precludes study entry.;12.is pregnant or breast feeding. ;13.is allergic to fosaprepitant, aprepitant, ondansetron, or any other 5-HT3 antagonist.;14.has a known history of QT prolongation or is taking any medication that is known to lead to QT prolongation. ;15.has an active infection (e.g., pneumonia), congestive heart failure, bradyarrythmia, any uncontrolled disease (e.g., 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 drug or concomitant therapy to the subject.;16.has ever participated in a previous study of aprepitant or fosaprepitant or has taken a non-approved (investigational) drug within the last 4 weeks. Note: Subjects in investigational studies with marketed chemotherapeutic agents (whether explicitly for children or only marketed for adults and usually administered in children with the appropriate dose adjustments) are allowed to enroll if they fulfill all other entry criteria. Previous or current participation in an observational study is acceptable.;17.is currently taking, or has taken a CYP3A4 inducer (within 30 days of Treatment Day 1), a CYP3A4 substrate or inhibitor (within 7 days of Treatment Day 1) or is expected to receive within 120 hours following initiation of chemotherapy. Or, is currently taking warfarin or is expected to receive within 2 weeks following initiation of chemotherapy;Refer to Protocol for complete list