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

Immune Oncology Research Institute

Status and phase: Enrolling; Phase 3

Conditions: Pediatric Cancer

Treatments: Drug: Ondansetron; Drug: Dexamethasone

Study type: Interventional

Funder types: Other

Identifiers

NCT05872893

IMMONC0009

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: Under 18 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

---

40 participants in 2 patient groups

ondansetron + dexamethasone, continuous infusion

Experimental group

Description:

Patients will receive a continuous infusion of age-adjusted doses of first-generation 5-HT3 receptor antagonist ondansetron in combination with dexamethasone

Treatment:

Drug: Dexamethasone

Drug: Ondansetron

ondansetron + dexamethasone, push injection

Active Comparator group

Description:

Patients will receive standard i/v push injections of first-generation 5-HT3 receptor antagonist ondansetron and dexamethasone

Treatment:

Drug: Dexamethasone

Drug: Ondansetron