Continuous Infusion of First-Generation 5-HT3 Receptor Antagonists in Combination With Dexamethasone

Phase 3

Recruiting

• Conditions: Pediatric Cancer
• Interventions: Drug: Ondansetron; Drug: Dexamethasone

• Registration Number: NCT05872893
• Lead Sponsor: Immune Oncology Research Institute

Brief Summary

Chemotherapy-induced nausea and vomiting are serious side effects of cancer treatment that can have a significant negative impact on a patient's quality of life. Although the prevalence of nausea and vomiting has significantly decreased due to the implementation of new antiemetic drugs, several studies revealed that approximately 30% to 60% of patients still complain of acute or delayed chemotherapy-induced emesis. It is estimated that slow infusion of ondansetron in combination with dexamethasone can provide long-lasting stable concentrations of drugs in the blood serum contributing to better effect development. Therefore, the investigators suggest a continuous infusion of the above-mentioned drug combination as an alternative with potential superior activity.

Detailed Description

Chemotherapy-induced nausea and vomiting are serious side effects of cancer treatment that can have a significant negative impact on a patient's quality of life. It is estimated that 70-80% of patients receiving different chemotherapy regimens can experience emesis. Although the prevalence of nausea and vomiting has significantly decreased due to the implementation of new antiemetic drugs, several studies revealed that approximately 30% to 60% of patients still complain of acute or delayed chemotherapy-induced emesis. Currently, the three categories of drugs with the highest therapeutic index for preventing chemotherapy-induced nausea and vomiting are 5-HT3 receptor antagonists, NK1 receptor antagonists, and glucocorticoids (particularly Dexamethasone). Second-generation 5-HT3 receptor antagonists and NK1 receptor antagonists are more effective due to their prolonged influence but are very expensive and not available in the majority of resource-limited settings. Moreover, NK1 receptor antagonists are not still widely recommended for use in children \< 12 years of age. First-generation 5-HT3 receptor antagonists in combination with Dexamethasone have proven superior activity compared to single agents. It is estimated that slow infusion of the above-mentioned agents can provide long-lasting stable concentrations of drugs in the blood serum contributing to better effect development. It has been shown that Ondansetron continuous infusion has superior efficacy in preventing postsurgical nausea and vomiting. Therefore, the investigators suggest a continuous infusion of first-generation 5-HT3 receptor antagonists in combination with Dexamethasone as an alternative with potential superior activity.

Study Timeline

• Study First Submitted: 2023-05-15
• Study First Submitted QC: 2023-05-23
• Study First Posted: 2023-05-24
• Study Start: 2023-06-27
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-20
• Last Update Posted: 2023-07-21
• Primary Completion: 2025-01
• Study Completion: 2025-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Patients aged from 1 day to 18 years who are diagnosed with cancer and are eligible for chemotherapy.
• Voluntarily agree to participate by giving written parental permission and child assent.
• Patients with sufficient cardiac function, as determined by the investigator.

Exclusion Criteria

• Patients with a history of severe hypersensitivity reactions or anaphylaxis related to the use of 5-HT3 receptor antagonists.
• Patients receiving concurrent chemo-radiation therapy.
• Patients diagnosed with cardiac arrhythmias and congenital long QT interval syndrome.
• Known clinically significant drug interactions between chemotherapeutic agents and 5-HT3 receptor antagonists and/or Dexamethasone (e.g. more than 0.8 mg/ml concentrations of 5-fluorouracil may cause precipitation of ondansetron).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
ondansetron + dexamethasone, continuous infusion	Dexamethasone	Patients will receive a continuous infusion of age-adjusted doses of first-generation 5-HT3 receptor antagonist ondansetron in combination with dexamethasone
ondansetron + dexamethasone, continuous infusion	Ondansetron	Patients will receive a continuous infusion of age-adjusted doses of first-generation 5-HT3 receptor antagonist ondansetron in combination with dexamethasone
ondansetron + dexamethasone, push injection	Ondansetron	Patients will receive standard i/v push injections of first-generation 5-HT3 receptor antagonist ondansetron and dexamethasone
ondansetron + dexamethasone, push injection	Dexamethasone	Patients will receive standard i/v push injections of first-generation 5-HT3 receptor antagonist ondansetron and dexamethasone

Primary Outcome Measures

Name	Time	Method
Mean nausea score per patient	20 months	Mean nausea score will be calculated as a weighted average of the Visual Analogue Scale (VAS) or Baxter Animated Retching Faces (BARF) scale observations during each cycle of chemotherapy.

Secondary Outcome Measures

Name	Time	Method
Correlation between mean nausea score and demographic variables	20 months
Correlation between mean nausea score and disease characteristics	20 months

Trial Locations

Locations (1)

Hematology Center named after prof. R. Yeolyan; 🇦🇲 Yerevan, Armenia