Clinical trial NCT05872893: Continuous Infusion of First-Generation 5-HT3 Receptor Antagonists in Combination With Dexamethasone
Official title: Continuous Infusion of First-Generation 5-HT3 Receptor Antagonists in Combination With Dexamethasone. Can This Modality Improve the Antiemetic Effect
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Pediatric Cancer
Lead sponsor: Immune Oncology Research Institute
Sponsor class: OTHER
First posted: 2023-05-24
Enrollment: 40
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Each patient will serve as his or her own control. Study participants will be randomly assigned to the sequence of treatment. If the patient is assigned to the experimental arm during the first cycle of chemotherapy, he or she will receive the comparator treatment during the second cycle and vice versa. Treatment modalities will follow each other throughout the whole study period.

Mean nausea score during each chemotherapy cycle will be calculated. To achieve statistically significant results, 140 chemotherapy cycles must be included in the analysis.
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Mean nausea score per patient
timeFrame: 20 months
Secondary outcomes:
measure: Correlation between mean nausea score and demographic variables
timeFrame: 20 months
measure: Correlation between mean nausea score and disease characteristics
timeFrame: 20 months
Other outcomes:
Locations:
city: Yerevan
country: Armenia
facility: Hematology Center named after prof. R. Yeolyan
Study officials:
affiliation: Immune Oncology Research Institute
name: Julieta Hoveyan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Immune Oncology Research Institute
name: Ruzanna Papyan, MD
role: STUDY_CHAIR
affiliation: Immune Oncology Research Institute
name: Samvel Bardakhchyan, MD, PhD
role: STUDY_CHAIR
affiliation: Immune Oncology Research Institute
name: Gevorg Tamamyan, MD, PhD, DSc
role: STUDY_DIRECTOR
References: