Study protocol for a double-blind, comparative, randomised Japanese trial of triplet standard antiemetic therapies with or without 5 mg olanzapine to prevent chemotherapy-induced nausea and vomiting for patients with breast cancer treated with an anthracycline/cyclophosphamide regimen (JTOP-B)

INTRODUCTION: Triple antiemetic therapy with neurokinin-1 receptor antagonist, 5-hydroxytryptamine type 3 receptor antagonist, and dexamethasone has been widely recommended for high emetogenic chemotherapeutic (HEC) agents and regimens, including anthracycline combined with cyclophosphamide (AC). The addition of olanzapine (OLZ) 5 mg or 10 mg to the recommended triple antiemetic therapy has demonstrated superiority in antiemetic efficacy compared with the standard triplet therapy for a cisplatin-based HEC regimen. Although OLZ plus the triple antiemetic treatment may also be effective for patients on an AC-based HEC regimen, no study has investigated its efficacy at a lower dose of 5 mg. METHODS AND ANALYSIS: To assess whether 5 mg OLZ, as compared with placebo, in combination with triple combination therapy, significantly improves nausea and vomiting, we are conducting a randomised, parallel-group controlled clinical trial with a total of 500 patients at 15 study centres in Japan. The primary outcome is the complete response rate, defined as no emetic episodes and no use of rescue medication during 120 hours after the initiation of chemotherapy. Treatment group comparison for the primary endpoint will be done by using the Cochran-Mantel-Haenszel test. ETHICS AND DISSEMINATION: The study was approved by the institutional review board of Juntendo University Hospital and relevant approval was obtained from all participating centres. All participants will be required to provide written informed consent. The trial results will be reported at conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Japan Registry of Clinical Trials (jRCT) jRCT1031200134; protocol date: 30 July 2020, version: 1.3, approval: 25 August 2020.