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

Chemotherapy Induced Nausea and Vomiting Clinical Trial

Official title:

Comparative Study of Fosaprepitant and Aprepitant for the Prevention of Chemotherapy-induced Nausea and Vomiting in Pediatric Cancer Patients：A Superiority Design, Phase III Randomized Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04873284
• Other study ID #: Fosaprepitant and aprepitant
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 1, 2021
• Est. completion date: December 30, 2021

Study information

• Verified date: May 2021
• Source: Shanghai Children's Medical Center
• Contact: Li-Ting Yu, MD
• Phone: 021-38626161
• Email: yuliting[@]scmc.com.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: December 30, 2021
• Est. primary completion date: December 25, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 12 Years

Eligibility

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

Related Conditions & MeSH terms

• Chemotherapy Induced Nausea and Vomiting
• Nausea
• Pediatric Cancer Patients
• Vomiting

Intervention

Drug:
• fosaprepitant
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
• aprepitant
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).
• Granisetron plus dexamethasone
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.

Locations

Country	Name	City	State
China	Shanghai Children's Medical Center	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Children's Medical Center

Country where clinical trial is conducted

China, 

References & Publications (5)

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Complete Remission rates in the delayed and overall phases	Complete Remission rates in the delayed and overall phases	up to 6 months
Secondary	Adverse events reported in study patients	All of the adverse reactions of aprepitant and fosaprepitant during the study.	up to 6 months