Anti-Emetic Prophylaxis for Chemotherapy-Induced Nausea and Vomiting with Fosaprepitant for Children and Adolescents Receiving Moderately Emetogenic Chemotherapy: An Investigator-Initiated, Double-blinded, Superiority, Phase III Randomized Controlled Trial.
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 192
- 试验地点
- 1
- 主要终点
- 1.To estimate and compare the proportion of patients with complete response (CR) for vomiting during the overall period between triple drug regimen (DPF) and two drug regimen for CINV prophylaxis (DP).
研究概览
简要总结
Review of Literature:
The recently published clinical practice guidelines (CPG) for prevention of acute and delayed CINV in pediatric cancer patients strongly recommends the combination of 5-Hydroxytryptamine receptor antagonist (5HT3RA) and dexamethasone to prevent acute phase CINV among children receiving moderately emetogenic chemotherapy (MEC). However, this recommendation is based on meta-analysis of 3 randomised controlled trials (RCTs) among adult patients comparing 5HT3RA and dexamethasone with 5HT3RA alone (RR 1.29, 95% CI: 1.21–1.39).
Based on the meta-analysis of 11 RCTs comprising of no pediatric patients, the recent CPG concluded that triple drug prophylaxis with 5HT3RA, dexamethasone, and neurokinin-1 (NK-1) antagonist provided no added benefit compared with dual agent (5HT3RA and dexamethasone) prophylaxis in acute phase CIV control (RR 1.03, 95% CI: 1.00–1.07) or acute phase CIN control (RR 1.02, 95% CI: 0.91–1.16). This is in contrary to the results of a subgroup analysis of our previous trial which compared three drug (ondansetron, dexamethasone and fosaprepitant) with two drug (ondansetron and dexamethasone) anti-emetic prophylaxis for children receiving MEC [CR rate of acute CINV: 92% vs 67%; (p value = 0.001)].
Rationale for the study:
· After the review of literature, we identified the lacunae of pediatric specific data supporting the recommendation of anti-emetic prophylaxis for children receiving MEC.
Despite the guideline consistent anti-emetic prophylaxis with Dexamethasone and 5HT3 RA, 30-40% of patients receiving MEC still experience breakthrough vomiting. Aprepitant and Fosaprepitant are the other potent anti-emetic agents, which has shown its efficacy in children receiving HEC. Since the recommended doublet anti-emetic prophylactic regimen has not reduced the incidence of CINV to the desirable level of <10%, we propose to study the benefit of adding Fosaprepitant to the standard two drug prophylaxis among children receiving MEC. This study may help to optimize the anti-emetic prophylaxis for children receiving MEC, thereby ensuring emesis free chemotherapy delivery. This study may contribute to the pediatric specific evidence required for formulating the CINV prophylactic guidelines for children.
RESEARCH QUESTION
Does the triple drug regimen (DPF) for CINV prophylaxis improve the complete response rate during the overall period by 20% (from 50% to 70%) compared to the two-drug regimen (DP) in children aged 4 years to 18 years receiving MEC on a single day regimen?
HYPOTHESIS
· Null hypothesis (H0):Triple drug DPF regimen for CINV prophylaxis does not result in improvement of complete response rate during the overall period by 20% (from 50% to 70%) compared to the two-drug regimen (DP) in children aged 4 years to 18 years receiving MEC.
· Alternate hypothesis (HA): Triple drug DPF regimen for CINV prophylaxis results in improvement of complete response rate during the overall period by 20% (from 50% to 70%) compared to the two-drug regimen (DP) in children aged 4 years to 18 years receiving MEC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Stratified block randomization
- 盲法
- Participant and Outcome Assessor Blinded
入排标准
- 年龄范围
- 4.00 Year(s) 至 18.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Age between 4 to 18 years and diagnosed with cancer.
- •Patients under four years have not been included as nausea assessment cannot be performed.
- •2.Receiving single-day regimen of moderately emetogenic chemotherapy (MEC).
- •3.Patients could have received prior chemotherapy.
- •They need not be chemotherapy naïve.
- •4.Lansky play performance score of 60 or more for less than 16 years.
- •Eastern Cooperative Oncology Group performance status of 0, 1, or 2 for 16-18 years.
- •5.Adequate organ function as confirmed by laboratory investigations within two weeks [Aspartate transaminase (AST) and Alanine transaminase (ALT) within four times upper limit of normal (ULN), serum bilirubin less than 2 mg/dL, serum creatinine within ULN].
- •6.Written informed consent from parents before enrollment.
- •Children above 7-12 years of age will need to provide verbal assent.
排除标准
- •1.Benzodiazepines or opioids are initiated 48 hours before treatment, except for single doses of triazolam, temazepam, or midazolam.
- •2.History of vomiting 24 hours before enrollment.
- •3.Use of antiemetics within 48 hours before treatment.
- •4.Patients receiving corticosteroids as a part of their chemotherapy protocol.
- •5.Patients with a primary brain tumor or brain metastasis.
- •6.Patients receiving concurrent radiotherapy with chemotherapy.
- •7.Patients in whom there are contraindications for corticosteroid use like uncontrolled diabetes mellitus, uncontrolled hypertension, active peptic ulcer disease and gastrointestinal bleeding.
- •8.History of allergy to any of the drugs used for anti-emetic prophylaxis.
- •9.Pregnant or breastfeeding patients.
结局指标
主要结局
1.To estimate and compare the proportion of patients with complete response (CR) for vomiting during the overall period between triple drug regimen (DPF) and two drug regimen for CINV prophylaxis (DP).
时间窗: 0-120 hrs
次要结局
- 1.To compare the proportion of patients with complete response (CR) rates for vomiting during the acute period between triple drug regimen (DPF) and two drug regimen (DP) for CINV prophylaxis.(0-24 hrs)
- 2.To compare the proportion of patients with complete response (CR) rates for vomiting during the delayed period between triple drug regimen (DPF) and two drug regimen (DP) for CINV prophylaxis(24-120 hrs)
- 3.To compare the proportion of patients with CR to nausea for the overall, acute and delayed period period between triple drug regimen (DPF) and two drug regimen (DP) for CINV prophylaxis.(0-120 hrs)
- 4.To compare the grade 3 and grade 4 toxicities between the two regimens(0-120 hrs)