Efficacy and Safety of Fosaprepitant in Preventing Chemotherapy-induced Vomiting in Children Treated With Medium and High Emetic Chemotherapeutic Drugs

Overview

This study was a prospective, randomized, double-blind, parallel controlled clinical trial. The children who met the inclusion criteria and were treated with medium and high emetic chemotherapy drugs were randomly included in the experimental group (forsapitan group) and the control group (placebo group) in the ratio of 1 ∶ 1. The children in the experimental group were infused with fosapitan, dexamethasone and granisetron before chemotherapy, and then continued to be infused with granisetron and dexamethasone until 48 hours after the end of chemotherapy. The antiemetic regimen of children in the control group was placebo instead of fosapitan, and the others were the same as those in the experimental group. In this study, CNNC antiemetic scale and pediatric scale proposed by Dupuis were used to evaluate the vomiting data. The primary end point was the proportion of children who achieved complete remission (CR) in the delayed period (within 24-120 hours after the start of chemotherapy); The secondary end points were the CR rate in the acute phase (within 24 hours after the first chemotherapy administration) and the overall phase. The antiemetic efficacy and adverse reactions of the two groups were observed and analyzed.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Single (Investigator)
  • Study Primary Completion Date: April 1, 2022

Interventions

  • Drug: Fosaprepitant
    • Fosaprepitant: 4 mg/kg IV Granisetron+dexamethasone: granisetron:40mcg/kg, IV ; dexamethasone : S<0.6m2, 2 mg/dose, q12h IV/PO; S>0.6m2, 4 mg/dose, q12h , IV/PO. When used with fosaprepitant, dexamethasone dose was halved.
  • Drug: Placebo(normal saline)
    • Placebo(normal saline): 4 ml/kg IV Granisetron+dexamethasone: granisetron:40mcg/kg, IV ; dexamethasone : S<0.6m2, 2 mg/dose, q12h IV/PO; S>0.6m2, 4 mg/dose, q12h , IV/PO.

Arms, Groups and Cohorts

  • Experimental: fosaprepitant
    • Patients received intravenous Ganisetron plus dexamethasone followed by fosaprepitant infusion
  • Placebo Comparator: Placebo
    • Patients received intravenous Ganisetron plus dexamethasone followed by normal saline

Clinical Trial Outcome Measures

Primary Measures

  • Complete remission rates in the acute phases
    • Time Frame: up to 6 months
    • The primary end point was complete remission rates in the acute phase. Complete Remission was defined as no vomiting, no retching, and no use of rescue medecation

Secondary Measures

  • Complete Remission rates in the delayed and overall phases
    • Time Frame: up to 6 months
    • Complete Remission rates in the delayed and overall phases
  • Adverse events reported in study patients
    • Time Frame: up to 6 months
    • All of the adverse reaction of aprepitant and fosaprepitant during the study

Participating in This Clinical Trial

Inclusion Criteria

  • children aged 2-12 years at the time of study entry with documented cancer scheduled to receive MEC or HEC (more than 30% emetogenic potential) with Karnofsky score of 60 or more (for patients aged greater than 10 years) or Lansky play performance score of 60 or more (for patients aged 10 years or less) predicted life expectancy of at least 3 months; and written informed consent provided by parent or guardian Exclusion Criteria:

  • vomiting 24 hours before treatment day 1 known history of QT prolongation or allergic reaction to any of the study drugs symptomatic primary or metastatic CNS malignancy causing nausea or vomiting patients who received radiation therapy to the abdomen or pelvis in the week before treatment; active infection or any uncontrolled concurrent illness except for malignancy abnormal laboratory values at screening (peripheral absolute neutrophil count <1000 cells per μL, platelet count <100 000 cells per μL; alanine amino transferase or aspartate aminotransferase >5 times of the upper limit of normal for age, bilirubin or serum creatinine >1.5 times of the upper limit of normal for age) initiation of systemic corticosteroids within 72 hours before study drug administration or as part of the chemotherapy regimen; benzodiazepines or opioids initiated within 48 hours before treatment, except for single doses of triazolam, temazepam, or midazolam use of antiemetics within 48 hours of treatment use of CYP3A4 substrates or inhibitors within 7 days or CYP3A4 inducers within 30 days of treatment

Gender Eligibility: All

Minimum Age: 2 Years

Maximum Age: 12 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Shanghai Children’s Medical Center
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Yijin Gao, Study Director, Shanghai Children’s Medical Center
  • Overall Contact(s)
    • Liting Yu, 13636303912, yuliting20091396@163.com

References

Flank J, Robinson PD, Holdsworth M, Phillips R, Portwine C, Gibson P, Maan C, Stefin N, Sung L, Dupuis LL. Guideline for the Treatment of Breakthrough and the Prevention of Refractory Chemotherapy-Induced Nausea and Vomiting in Children With Cancer. Pediatr Blood Cancer. 2016 Jul;63(7):1144-51. doi: 10.1002/pbc.25955. Epub 2016 Mar 9.

Weinstein C, Jordan K, Green SA, Camacho E, Khanani S, Beckford-Brathwaite E, Vallejos W, Liang LW, Noga SJ, Rapoport BL. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: results of a randomized, double-blind phase III trial. Ann Oncol. 2016 Jan;27(1):172-8. doi: 10.1093/annonc/mdv482. Epub 2015 Oct 8.

Radhakrishnan V, Joshi A, Ramamoorthy J, Rajaraman S, Ganesan P, Ganesan TS, Dhanushkodi M, Sagar TG. Intravenous fosaprepitant for the prevention of chemotherapy-induced vomiting in children: A double-blind, placebo-controlled, phase III randomized trial. Pediatr Blood Cancer. 2019 Mar;66(3):e27551. doi: 10.1002/pbc.27551. Epub 2018 Nov 13.

Mora J, Valero M, DiCristina C, Jin M, Chain A, Bickham K. Pharmacokinetics/pharmacodynamics, safety, and tolerability of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in pediatric cancer patients. Pediatr Blood Cancer. 2019 Jun;66(6):e27690. doi: 10.1002/pbc.27690. Epub 2019 Mar 21.

Dupuis LL, Boodhan S, Holdsworth M, Robinson PD, Hain R, Portwine C, O'Shaughnessy E, Sung L; Pediatric Oncology Group of Ontario. Guideline for the prevention of acute nausea and vomiting due to antineoplastic medication in pediatric cancer patients. Pediatr Blood Cancer. 2013 Jul;60(7):1073-82. doi: 10.1002/pbc.24508. Epub 2013 Mar 19.

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