Comparative Study of Fosaprepitant and Aprepitant for the Prevention of Chemotherapy-induced Nausea and Vomiting in Pediatric Caner Patients

NCT04873284 | Unknown

• 1 other identifier: Fosaprepitant and aprepitant
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Children aged 2-12 years scheduled to receive moderately or highly emetogenic chemotherapy were randomly assigned to arm-A (fosaprepitant) or arm-B (aprepitant). Children recruited to arm-A received intravenous granisetron plus dexamethasone followed by fosaprepitant infusion. Children recruited to arm-B received the same drugs as those given to children in arm-A, except that fosaprepitant was substituted with aprepitant. Granisetron and dexamethasone were given continuously until 48 hours after completion of chemotherapy. The primary end point of the study was to determine the proportion of patients who achieved a CR, defined as no vomiting, no retching, and no use of rescue medication, the proportion of patients who achieved a CR during the acute phase (0-24 hours) after administration of the last dose of chemotherapy. Secondary end points were the proportion of patients who achieved a CR during the 24-120 hours (delayed phase) and overall after administration of the last dose of chemotherapy.

Conditions

Chemotherapy Induced Nausea and Vomiting; Pediatric Cancer Patients

Keywords

fosaprepitant; aprepitant; pediatric cancer; vomiting; efficacy; safety

Outcome Measures

Primary Outcomes (1)

• Complete Remission rates in the acute phases

  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 medication

  up to 6 months

Secondary Outcomes (2)

• Complete Remission rates in the delayed and overall phases

  up to 6 months

• Adverse events reported in study patients

  up to 6 months

Study Arms (2)

Fosaprepitant

EXPERIMENTAL

Patients received intravenous Granisetron plus dexamethasone followed by fosaprepitant infusion

Drug: fosaprepitant; Drug: Granisetron plus dexamethasone

Aprepitant

EXPERIMENTAL

Patients received intravenous Granisetron plus dexamethasone followed by oral aprepitant

Drug: aprepitant; Drug: Granisetron plus dexamethasone

Interventions

fosaprepitant DRUG

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. Fosaprepitant: 4 mg/kg IV

Fosaprepitant

aprepitant DRUG

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 aprepitant, dexamethasone dose was halved. Oral aprepitant: D1：Powder for suspension 3.0 mg/kg (up to 125 mg),D2，D3：Powder for suspension 2.0 mg/kg (up to 80 mg).

Aprepitant

Granisetron plus dexamethasone DRUG

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.

Aprepitant; Fosaprepitant

Eligibility Criteria

• Age: 2 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shanghai Children's Medical Center: lead

Study Sites (1)

Shanghai Children's Medical Center

Shanghai, China

Location

Related Publications (6)

• 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.

  PMID: 26960036 BACKGROUND

• 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.

  PMID: 26449391 BACKGROUND

• 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.

  PMID: 30426714 BACKGROUND

• 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.

  PMID: 30900392 BACKGROUND

• 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.

  PMID: 23512831 BACKGROUND

• Yu LT, Wang Z, Han YL, Zhou F, Wagner LM, Zhang SG, Li ZL, Gao YJ. Comparison of oral aprepitant and intravenous fosaprepitant for prevention of chemotherapy-induced nausea and vomiting in pediatric oncology patients: a randomized phase III trial. Transl Pediatr. 2024 Jan 29;13(1):110-118. doi: 10.21037/tp-23-598. Epub 2024 Jan 12.

  PMID: 38323173 DERIVED

MeSH Terms

Conditions

Vomiting; Neoplasms

Interventions

fosaprepitant; Aprepitant; Granisetron; Dexamethasone

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Indazoles; Pyrazoles; Azoles; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Yi-Jin Gao

  Shanghai Children's Medical Center

  STUDY DIRECTOR

Central Study Contacts

Li-Ting Yu, MD

CONTACT

021-38626161; yuliting@scmc.com.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2021
• First Posted: May 5, 2021
• Study Start: May 1, 2021
• Primary Completion: December 25, 2021
• Study Completion: December 30, 2021
• Last Updated: May 10, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)