Chemotherapy-induced nausea and vomiting (CINV) associated with emetogenic chemotherapy MedDRA version: 15.0 Level: LLT Classification code 10036899 Term: Prophylaxis against chemotherapy induced vomiting System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Trade Name: IVEMEND
Product Name: fosaprepitant
Product Code: MK-0517
Pharmaceutical Form: Lyophilisate and solvent for suspension for injection
INN or Proposed INN: FOSAPREPITANT
CAS Number: 172673-2
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patient is 0 (at least 37 weeks gestation) to 17 years of age at time of study entry (randomization). - Parent/guardian (legally authorized representative) agrees to the patients participation as indicated by parent/legal guardian signature on the informed consent form. Patient 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. The parent/guardian or patient may also provide consent/assent for Future Biomedical Research. However, the patient may participate in the main trial without participating in the Future Biomedical Research. - Patient is 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. - Female patient who has begun menses has a negative urine pregnancy test prior to randomization. A female patient who is of reproductive potential agrees to remain abstinent or use a barrier form of contraception for at least 14 days prior to, throughout, and for at least one month following the last dose of study medication. Women taking oral contraception must agree to add a barrier form of contraception. For countries where abstinence is not considered an acceptable method of birth control, a locally acceptable birth control method must be used. - Patient has a preexisting functioning central venous catheter available for study drug administration. - Patients weight should not be less than the 3rd percentile for age and gender (and no less than 3.0 kg) per investigator judgment using available local growth chart(s). Are the trial subjects under 18? yes Number of subjects for this age range: 256 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Patient has vomited in the 24 hours prior to chemotherapy initiation on Treatment Day 1. - Patient is currently a user of any illicit drugs (including marijuana) or has current evidence of alcohol abuse (defined using the Diagnostic and Statistical Manual-IV [DSM-IV] criteria) as determined by the investigator. - Patient has received or will receive radiation therapy to the abdomen or pelvis in the week prior to Treatment Day 1 and/or during the course of the study. - Patient is allergic to fosaprepitant, aprepitant, ondansetron, or any other 5-HT3 antagonist. - Patient has an active infection (e.g., pneumonia), congestive heart failure, bradyarrythmia, any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction) except for malignancy, or a history of 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 patient. - Patient is mentally incapacitated or has a significant emotional or psychiatric disorder that, in the opinion of the investigator, precludes study entry. - Patient has a known history of QT prolongation or is taking any medication that is known to lead to QT prolongation. - Patient has had benzodiazepine or opioid therapy initiated within 48 hours of study drug administration, except for single daily doses of triazolam, temazepam, or midazolam. * Continuation of chronic benzodiazepine or opioid therapy is permitted provided it was initiated at least 48 hours prior to study drug administration. - Patient has been started on systemic corticosteroid therapy within 72 hours prior to study drug administration or is planned to receive a corticosteroid as part of the chemotherapy regimen. Exceptions: ? Patients who are 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, patients are 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. - Patient is currently taking warfarin. - Patient has ever participated in a study of aprepitant or fosaprepitant, or has taken a non-approved (investigational) drug within the last 4 weeks. Note: Patients in investigational studies with marketed chemotherapeutic agents (whether explicitly for children or only marketed for adults and usually administered to children with the appropriate dose adjustments) are allowed to enroll if they fulfill all other entry criteria.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the appropriate dosing regimen of fosaprepitant for the prevention of CINV in pediatric patients birth to 17 years of age, by assessing the pharmacokinetic and pharmacodynamic parameters, and the safety and tolerability of the administered dose of fosaprepitant, concomitantly with IV ondansetron, in patients from birth to 17 years of age receiving emetogenic chemotherapy (very highly emetogenic chemotherapy [VHEC], highly emetogenic chemotherapy [HEC], or moderately emetogenic chemotherapy [MEC]), or a chemotherapy regimen not previously tolerated due to vomiting, for a documented malignancy.;Secondary Objective: The efficacy, with respect to Complete Response and No Vomiting, of the fosaprepitant regimen when administered concomitantly with ondansetron, with or without dexamethasone, will be explored in pediatric patients birth to 17 years of age receiving emetogenic chemotherapy (VHEC, HEC, or MEC), or a chemotherapy regimen not previously tolerated due to vomiting, for a documented malignancy.;Primary end point(s): - Pharmacokinetic (PK) Endpoints: Cmax, Tmax, AUC0-infinity, t1/2, CL/F estimated by population methods, including the use of historic data in population modeling, in each age group for the 3 fosaprepitant treatment groups in Cycle 1. - Safety Endpoints: Clinical and laboratory adverse events that are considered drug-related, serious, serious drug-related, or lead to discontinuation of study therapy.;Timepoint(s) of evaluation of this end point: For PK: Five scheduled time points for PK sampling 1. End of the fosaprepitant infusion 2. 2 to 4 hours after (completion of) fosaprepitant dosing 3. 5 to 7 hours after fosaprepitant dosing 4. 8 to 10 hours after fosaprepitant dosing 5. 23 to 25 hours after fosaprepitant dosing For Safety: Throughout the study (Screening, Treatment, Post-Treatment, and/or Follow-Up/DC). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Pharmacodynamic (PD) Endpoints: The proportion of patients with Complete Response (CR) in the 25 to 120 hours after initiation of chemotherapy (delayed phase). Other PD endpoints will be the proportion of patients with CR in the 0 to 24 hours after chemotherapy (acute phase); and the proportion of patients with CR in the 0 to 120 hours after chemotherapy (overall phase); and also, the proportion of patients with No Vomiting. Irrespective of use of rescue medication, in the overall, acute, and delayed phases.;Timepoint(s) of evaluation of this end point: For PD: Over the first 120 hours (to Day 6) following the initiation of chemotherapy (Tzero). | — |
Countries
Argentina, Austria, Brazil, Canada, Chile, Colombia, Estonia, Germany, Greece, Hungary, India, Italy, Lithuania, Mexico, Peru, Portugal, Romania, Russian Federation, South Africa, Spain, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactEduardo Portuondo
Merck, Sharp & Dohme de España, S.A.
Outcome results
None listed