A Multicentric, Phase 3 Randomized Controlled Trial (RCT) of Olanzapine as Antiemetic Prophylaxis in Moderately Emetogenic Chemotherapy

Chemotherapy-induced nausea and vomiting (CINV) remain one of the most distressing adverse effects of cancer chemotherapy and significantly affects patients’ quality of life, treatment adherence, and outcomes. Despite advances in guideline-based antiemetic prophylaxis using a 5-HT3 receptor antagonist and dexamethasone, with or without an NK-1 receptor antagonist, nausea—particularly delayed nausea—continues to be inadequately controlled in patients receiving moderately emetogenic chemotherapy (MEC). Most evidence for olanzapine as an antiemetic has been generated in highly emetogenic chemotherapy, while confirmatory data in MEC, especially from Indian populations, remain limited.

This is a multicentric, randomized, open-label, parallel-group, active-controlled Phase III clinical trial designed to evaluate the efficacy and safety of low-dose olanzapine as an add-on antiemetic prophylaxis in adult patients receiving MEC. Eligible patients will be randomized in a 1:1 ratio to receive either standard guideline-based antiemetic prophylaxis alone or standard prophylaxis plus olanzapine 5 mg orally once daily from Day 1 to Day 5 of chemotherapy.

The primary objective is to compare the proportion of patients achieving complete response, defined as no emesis, no use of rescue antiemetic medication, and minimal nausea, during the assessment period of 0–120 hours following chemotherapy. Secondary objectives include evaluation of complete response in acute and delayed phases, severity of nausea using a visual analog scale, quality of life assessed by the Functional Living Index–Emesis questionnaire, use of rescue antiemetic medication, and safety assessed using CTCAE version 5.0. The study will use intention-to-treat analysis. Given the low dose and short duration of olanzapine, the anticipated risk is minimal.