A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Clinical Trial, Conducted Under In-House Blinding Conditions, to Examine the Efficacy and Safety of Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Pediatric Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 307
- 主要终点
- Percentage of Participants With a Complete Response in the Delayed Phase of Cycle 1
研究概览
简要总结
This study will compare the safety and efficacy of a three-day oral aprepitant regimen (aprepitant plus ondansetron) to ondansetron alone in the prevention of chemotherapy-induced nausea and vomiting (CINV) in the 120 hours following the initiation of chemotherapy in pediatric participants. Those who complete this first cycle of treatment and meet certain eligibility criteria will have the option of continuing for 5 additional cycles of open-label aprepitant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 6 Months 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Is 6 months to 17 years of age at time of study entry
- •Is scheduled to receive chemotherapeutic agent(s) associated with moderate, high risk or very high risk of vomiting for a documented malignancy, or a chemotherapy regimen not previously tolerated due to vomiting
- •Is expected to receive ondansetron as part of their antiemetic regimen
- •If female and has begun menses, must has a negative urine pregnancy test prior to
- •randomization. A female 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
- •If >10 years old, have a Karnofsky score ≥ 60; if ≤ 10 years have a Lansky Play Performance score ≥ 60
- •Have a predicted life expectancy of ≥ 3 months
- •Optional Cycles 2-6:
- •Participant has, in the opinion of the investigator, completed the preceding cycle of chemotherapy and related study procedures satisfactorily
排除标准
- •Has vomited in the 24 hours prior to Treatment Day 1
- •Is scheduled to receive stem cell rescue therapy in conjunction with study related course(s) of emetogenic chemotherapy
- •Has received or will receive radiation therapy to the abdomen or pelvis within a week prior to Treatment Day 1 or during the course of the study
- •Is pregnant or breast feeding
- •Is allergic to aprepitant, ondansetron, or any other 5-hydroxytryptamine type-3 receptor (5-HT3) antagonist
- •Has a symptomatic primary or metastatic CNS malignancy causing nausea and/or vomiting
- •History of QT prolongation or taking other medicinal products that lead to QT prolongation
- •Has an active infection (e.g., pneumonia), congestive heart failure, bradyarrhythmia, or any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction) except for malignancy, which in the opinion of the investigator, might confound the results of the study or pose unwarranted risk in administering study drug to the participant
- •Has had benzodiazepine or opioid therapy initiated within 48 hours of study drug administration, except for single daily doses of triazolam, temazepam, or midazolam
- •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
- •Is currently taking warfarin
- •Optional Cycles 2-6:
- •All exclusion criteria from Cycle 1 apply except for vomiting in the 24 hours prior to Treatment Day 1
研究组 & 干预措施
Aprepitant Regimen
Cycle 1:
Participants 12 to 17 years of age, Day 1: aprepitant 125 mg capsule orally (PO) + ondansetron, Days 2 to 3: aprepitant 80 mg capsule PO. Participants 6 months to <12 years of age, Day 1: aprepitant powder for suspension (PFS), 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: aprepitant PFS, 2.0 mg/kg (up to 80 mg).
Optional Cycles 2-6:
Open-label aprepitant administered in the same manner as in Cycle 1.
干预措施: Aprepitant 125 mg (Drug)
Aprepitant Regimen
Cycle 1:
Participants 12 to 17 years of age, Day 1: aprepitant 125 mg capsule orally (PO) + ondansetron, Days 2 to 3: aprepitant 80 mg capsule PO. Participants 6 months to <12 years of age, Day 1: aprepitant powder for suspension (PFS), 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: aprepitant PFS, 2.0 mg/kg (up to 80 mg).
Optional Cycles 2-6:
Open-label aprepitant administered in the same manner as in Cycle 1.
干预措施: Aprepitant 80 mg (Drug)
Aprepitant Regimen
Cycle 1:
Participants 12 to 17 years of age, Day 1: aprepitant 125 mg capsule orally (PO) + ondansetron, Days 2 to 3: aprepitant 80 mg capsule PO. Participants 6 months to <12 years of age, Day 1: aprepitant powder for suspension (PFS), 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: aprepitant PFS, 2.0 mg/kg (up to 80 mg).
Optional Cycles 2-6:
Open-label aprepitant administered in the same manner as in Cycle 1.
干预措施: Aprepitant powder for suspension (PFS) (Drug)
Aprepitant Regimen
Cycle 1:
Participants 12 to 17 years of age, Day 1: aprepitant 125 mg capsule orally (PO) + ondansetron, Days 2 to 3: aprepitant 80 mg capsule PO. Participants 6 months to <12 years of age, Day 1: aprepitant powder for suspension (PFS), 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: aprepitant PFS, 2.0 mg/kg (up to 80 mg).
Optional Cycles 2-6:
Open-label aprepitant administered in the same manner as in Cycle 1.
干预措施: Ondansetron (Drug)
Aprepitant Regimen
Cycle 1:
Participants 12 to 17 years of age, Day 1: aprepitant 125 mg capsule orally (PO) + ondansetron, Days 2 to 3: aprepitant 80 mg capsule PO. Participants 6 months to <12 years of age, Day 1: aprepitant powder for suspension (PFS), 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: aprepitant PFS, 2.0 mg/kg (up to 80 mg).
Optional Cycles 2-6:
Open-label aprepitant administered in the same manner as in Cycle 1.
干预措施: Emetogenic chemotherapy (Drug)
Control Regimen
Cycle 1: Participants 12 to 17 years of age, Day 1: matching placebo for aprepitant 125 mg capsule oral (PO) + ondansetron Days 2 to 3: matching placebo for aprepitant 80 mg capsule PO. Participants 6 months to <12 years of age, Day 1: matching placebo PFS: 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: matching placebo PFS: 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.
干预措施: Ondansetron (Drug)
Control Regimen
Cycle 1: Participants 12 to 17 years of age, Day 1: matching placebo for aprepitant 125 mg capsule oral (PO) + ondansetron Days 2 to 3: matching placebo for aprepitant 80 mg capsule PO. Participants 6 months to <12 years of age, Day 1: matching placebo PFS: 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: matching placebo PFS: 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.
干预措施: Placebo for Aprepitant 125 mg (Drug)
Control Regimen
Cycle 1: Participants 12 to 17 years of age, Day 1: matching placebo for aprepitant 125 mg capsule oral (PO) + ondansetron Days 2 to 3: matching placebo for aprepitant 80 mg capsule PO. Participants 6 months to <12 years of age, Day 1: matching placebo PFS: 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: matching placebo PFS: 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.
干预措施: Placebo for Aprepitant 80 mg (Drug)
Control Regimen
Cycle 1: Participants 12 to 17 years of age, Day 1: matching placebo for aprepitant 125 mg capsule oral (PO) + ondansetron Days 2 to 3: matching placebo for aprepitant 80 mg capsule PO. Participants 6 months to <12 years of age, Day 1: matching placebo PFS: 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: matching placebo PFS: 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.
干预措施: Placebo for Aprepitant PFS (Drug)
Control Regimen
Cycle 1: Participants 12 to 17 years of age, Day 1: matching placebo for aprepitant 125 mg capsule oral (PO) + ondansetron Days 2 to 3: matching placebo for aprepitant 80 mg capsule PO. Participants 6 months to <12 years of age, Day 1: matching placebo PFS: 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: matching placebo PFS: 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.
干预措施: Emetogenic chemotherapy (Drug)
结局指标
主要结局
Percentage of Participants With a Complete Response in the Delayed Phase of Cycle 1
时间窗: 25 to 120 hours after the start of chemotherapy
Delayed Phase was defined as 25-120 hours after the start of chemotherapy. Complete response was defined as no vomiting or retching and no use of rescue medication in the delayed phase of Cycle 1.
次要结局
- Percentage of Participants With a Complete Response in the Acute Phase of Cycle 1(0 to 24 hours after initiation of chemotherapy)
- Percentage of Participants With a Complete Response in the Overall Phase of Cycle 1(0 to 120 hours after initiation of chemotherapy)
- Percentage of Participants With No Vomiting in the Overall Phase of Cycle 1(0 to 120 hours after initiation of chemotherapy)