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

Continuous Infusion of First-Generation 5-HT3 Receptor Antagonists in Combination With Dexamethasone. Can This Modality Improve the Antiemetic Effect

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.

Study Overview

• Status: Recruiting
• Conditions: Pediatric Cancer
• Intervention / Treatment: Drug: Ondansetron; Drug: Dexamethasone

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 Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Julieta Hoveyan, MD; Phone Number: +374 (10) 283800; Email: julia.hoveyan95@gmail.com
• Study Contact Backup: Name: Ruzanna Papyan, MD; Phone Number: +374 (10) 283800; Email: ruzannapapyan92@gmail.com

Study Locations

• Armenia
  • Yerevan, Armenia, 0014
    • Recruiting
    • Hematology Center named after prof. R. Yeolyan
    • Contact: Julieta Hoveyan, MD; Phone Number: +374 (010) 283800; Email: julia.hoveyan95@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ondansetron + dexamethasone, continuous infusion; Patients will receive a continuous infusion of age-adjusted doses of first-generation 5-HT3 receptor antagonist ondansetron in combination with dexamethasone	Drug: Ondansetron; Patients will receive age-adjusted doses of ondansetron 5mg/m2; Drug: Dexamethasone; Patients will receive dexamethasone 4mg/m2
Active Comparator: ondansetron + dexamethasone, push injection; Patients will receive standard i/v push injections of first-generation 5-HT3 receptor antagonist ondansetron and dexamethasone	Drug: Ondansetron; Patients will receive age-adjusted doses of ondansetron 5mg/m2; Drug: Dexamethasone; Patients will receive dexamethasone 4mg/m2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean nausea score per patient	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.	20 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Correlation between mean nausea score and demographic variables	20 months
Correlation between mean nausea score and disease characteristics	20 months

Collaborators and Investigators

• Sponsor: Immune Oncology Research Institute
• Investigators: Principal Investigator: Julieta Hoveyan, MD, Immune Oncology Research Institute; Study Chair: Ruzanna Papyan, MD, Immune Oncology Research Institute; Study Chair: Samvel Bardakhchyan, MD, PhD, Immune Oncology Research Institute; Study Director: Gevorg Tamamyan, MD, PhD, DSc, Immune Oncology Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2023
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: May 15, 2023
• First Submitted That Met QC Criteria: May 23, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Actual): July 21, 2023
• Last Update Submitted That Met QC Criteria: July 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Serotonin Agents; Serotonin Antagonists; Serotonin 5-HT3 Receptor Antagonists; Antipruritics; Dexamethasone; Ondansetron
• Other Study ID Numbers: IMMONC0009

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No