Sample size calculation, Feasibility, and Safety profile with Olanzapine for preventing Radiation Induced Nausea and Vomiting: Pilot Study for phase III Randomized Placebo-controlled Trial – CTRI No/2022/01/039723

Radiotherapy-induced nausea and vomiting (RINV) significantly affects overall health outcomes in cancer patients. Olanzapine has substantial potential in controlling RINV by blocking multiple receptors that regulate vomiting. This pilot study aims to determine the appropriate sample size for the future main trial and assess the feasibility and safety of olanzapine in combination with ondansetron for initiating phase III randomized trial.

Prospective, randomized, placebo-controlled study to be conducted at tertiary care teaching hospital in South India. Based on a statistical thumb rule, we enrolled 24 patients, test group (n=12) and control group (n=12). Simple randomization was employed for allocating the patients to receive either a placebo plus ondansetron or olanzapine 5mg plus ondansetron. All the adverse drug reactions were observed and graded for intensity by the scale of CTCAE v5. An appropriate formula to determine the sample size was used based on the percentage of occurrence of nausea between two groups.

Nausea was less common in olanzapine arm (16.7%) than control group (41.7%) (p=0.371). and was found to be clinically significant. Both groups exhibit similar levels of toxicity. Patients in the control group reported grade 2 nausea (33.3%) where in patients in olanzapine arm reported grade 1 (16.7%) nausea. Additionally, 100% of the patients who were recruited complied with the treatment plan.

This pilot study confirms that olanzapine combined with ondansetron shows promise for managing RINV with a favourable safety profile. A full study enrolling with minimum sample size of 152 patients would be required to fully characterize the role of olanzapine in improving patient care during radiotherapy.