The Safety and Efficacy of Ondansetron in Reducing Immune Checkpoint Inhibitor-Related Toxicities

The Safety and Efficacy of Ondansetron in Reducing Immune Checkpoint Inhibitor-Related Toxicities: A Single-Center Randomized Controlled Clinical Trial

This study is a prospective, randomized, single-center randomized controlled clinical trial to investigate the safety and efficacy of ondansetron in reducing the toxicity associated with immune checkpoint inhibitor treatment. This study plans to enroll 134 patients with hepatocellular carcinoma who are scheduled to receive standard ICI treatment. This study will adopt the 2023 CSCO Guidelines for the Management of Immune checkpoint inhibitor-related toxicity as the main assessment criterion, and take the incidence and severity of irAEs as the main observation indicators to evaluate the effectiveness of ondansetron in reducing the toxicity related to immune checkpoint inhibitor treatment in patients with hepatocellular carcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma (HCC); IrAE
• Intervention / Treatment: Drug: ondansetron

• Study Type: Interventional
• Enrollment (Estimated): 134
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age: 18 to 80 years old, both male and female are acceptable.
2. The imaging or pathological diagnosis is hepatocellular carcinoma;
3. It is planned to carry out standard treatment for liver cancer, specifically including lenvatinib + tislelizumab or lenvatinib + pembrolizumab or atezolizumab + bevacizumab.
4. ECOG score: 0 to 2 points;
5. Expected survival period ≥12 weeks;

6. Baseline blood cell count tests and blood biochemistry must meet the following standards:

   White blood cell count ≥3.0×10^9/L; Hemoglobin ≥90 g/L; The absolute neutrophil count is ≥1.5×10^9/L; Platelet count ≥100×10^9/L; Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal (ULN). Total bilirubin ≤ twice ULN; Serum creatinine ≤ 1.5 times ULN; Albumin ≥30 g/L;

7. The subjects voluntarily joined this study, signed the informed consent form, had good compliance and cooperated with the follow-up.

Exclusion Criteria:

1. Those who have received treatment with ondansetron within 14 days;
2. Patients with autoimmune diseases;
3. Use of systemic glucocorticoids or other immunosuppressants within 14 days;
4. Those who have previously discontinued ICI treatment due to irAEs;
5. Those with severe liver dysfunction (Child-Pugh grade C);
6. Those with contraindications to ondansetron such as serotonin syndrome or phenylketonuria;
7. Patients allergic to ondansetron;
8. Those who are currently using drugs that may have serious interactions with ondansetron, such as apopmorphine;
9. The researcher evaluated that the patient was unable or unwilling to comply with the requirements of the research protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ondansetron Group; Standard treatment plan：For patients with hepatocellular carcinoma, the standard treatment plan for liver cancer is adopted, which specifically includes lenvatinib + tislelizumab or lenvatinib + pembrolizumab or atezolizumab + bevacizumab: Ondansetron: Maintained at 8mg/qd, orally, until disease progression or intolerance. Symptomatic treatments other than 5-HT3 receptor antagonists are permitted, and all concurrent medication situations should be recorded.	Drug: ondansetron; Ondansetron: Maintained at 8mg/qd, orally, until disease progression or intolerance.
No Intervention: Control Group; Standard treatment plan：For patients with hepatocellular carcinoma, the standard treatment plan for liver cancer is adopted, which specifically includes lenvatinib + tislelizumab or lenvatinib + pembrolizumab or atezolizumab + bevacizumab Symptomatic treatments other than 5-HT3 receptor antagonists are permitted, and all concurrent medication situations should be recorded.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence rate of irAEs	To evaluate whether the prophylactic use of ondansetron can reduce the incidence of immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitors (ICI). The evaluation criteria mainly refer to the "2023 CSCO Guidelines for the Management of Toxicity Related to Immune Checkpoint Inhibitors", with a focus on the incidence of all grades of irAEs and the incidence of severe irAEs at grade 3 and above. The monitoring scope covers liver and kidney functions, blood routine, cardiac function (electrocardiogram, myocardial injury markers), endocrine function (thyroid function, etc.) and imaging manifestations of pneumonia.	through study completion, an average of 1 year
The Severity of irAEs	To evaluate whether the prophylactic use of ondansetron can reduce the severity of immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitors (ICI). The evaluation criteria mainly refer to the "2023 CSCO Guidelines for the Management of Toxicity Related to Immune Checkpoint Inhibitors", with a focus on the incidence of all grades of irAEs and the incidence of severe irAEs at grade 3 and above. The monitoring scope covers liver and kidney functions, blood routine, cardiac function (electrocardiogram, myocardial injury markers), endocrine function (thyroid function, etc.) and imaging manifestations of pneumonia.	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective Response Rate，according to RECIST v1.1	through study completion, an average of 1 year
DCR	Disease Control Rate, according to RECIST v1.1	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Wenzhou Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): March 20, 2026
• Primary Completion (Estimated): December 20, 2026
• Study Completion (Estimated): June 20, 2027

Study Registration Dates

• First Submitted: January 3, 2026
• First Submitted That Met QC Criteria: January 26, 2026
• First Posted (Actual): February 2, 2026

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Imidazoles; Indoles; Heterocyclic Compounds, 3-Ring; Carbazoles; Ondansetron
• Other Study ID Numbers: KY2026-021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No