Background: Chemotherapy-induced nausea and vomiting (CINV) is a common adverse effect affecting quality of life of patients of cancer undergoing chemotherapy. Carboplatin alone or in combination with various other chemotherapy drugs is one of the most commonly used drug in solid malignancies. It is categorised as a highly emetogenic drug in doses above AUC≥4 and multiple past studies revealed high CINV incidence. Current international antiemetic guidelines suggest NK1 receptor antagonist based triplet drugs as an effective regimen of CINV control in these patients. However, the nausea control rates are largely inadequate. Olanzapine, an atypical antipsychotic drug, is another drug that has shown significant activity in CINV control and is an integral part of current chemotherapy induced emesis and nausea prevention. However, robust comparative studies of olanzapine based triplets with NK1 based combination have been lacking. Hence we planned this study to compare efficacy of olanzapine containing triplet with NK1 receptor antagonist (fosaprepitant) based triplet drug combination in a phase 3 randomised study. Methods: This study is an investigator initiated phase 3 prospective randomised double blind placebo controlled trial comparing efficacy of olanzapine, 5HT3 receptor antagonist(ondansetron) and dexamethasone (experimental arm) against fosaprepitant, 5HT3 receptor antagonist(ondansetron) and dexamethasone (standard arm) for prevention of CINV among chemo-naïve patients (aged ≥18 years) receiving carboplatin (AUC ≥4) based chemotherapy regimen. Primary objective is to compare the number of patients with no nausea during overall periods (0-120 hours post-chemotherapy). Secondary objectives are to compare complete response (no emetic episodes and no use of rescue medication) in the acute(0-24 hr), delayed(25-120 hr),overall periods(0-120 hr) and to assess the frequency of rescue medication use. The other secondary objective includes assessment of adverse events in both the arms. Statistical Design: Planned accrual is total 214 patients including 10% drop out rate. It is a superiority design with an absolute improvement of 20% in the proportion of patients with no nausea from a baseline prevalence of 40% in the standard arm and two sided alpha of 5% as well as power of 80%. Conduct to date :Study activation : March 2021. Enrolment : 138 subjects. Clinical trial information: CTRI/2021/03/032165.