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

NCT07381634 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: KY2026-021
• Study Type: interventional
• Target: 134
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Hepatocellular Carcinoma (HCC); IrAE

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• ORR

  through study completion, an average of 1 year

• DCR

  through study completion, an average of 1 year

Study Arms (2)

Ondansetron Group

EXPERIMENTAL

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

Control Group

NO INTERVENTION

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.

Interventions

ondansetron DRUG

Ondansetron: Maintained at 8mg/qd, orally, until disease progression or intolerance.

Ondansetron Group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18 to 80 years old, both male and female are acceptable.
• The imaging or pathological diagnosis is hepatocellular carcinoma;
• It is planned to carry out standard treatment for liver cancer, specifically including lenvatinib + tislelizumab or lenvatinib + pembrolizumab or atezolizumab + bevacizumab.
• ECOG score: 0 to 2 points;
• Expected survival period ≥12 weeks;
• 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;
• The subjects voluntarily joined this study, signed the informed consent form, had good compliance and cooperated with the follow-up.

You may not qualify if:

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

Sponsors & Collaborators

• First Affiliated Hospital of Wenzhou Medical University: lead

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Ondansetron

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Hepatobiliary Surgery, Clinical Professor, Vice President

Study Record Dates

• First Submitted: January 3, 2026
• First Posted: February 2, 2026
• Study Start: March 20, 2026
• Primary Completion (Estimated): December 20, 2026
• Study Completion (Estimated): June 20, 2027
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share