Clinical trial protocol of doublet therapy and olanzapine for carboplatin-induced nausea and vomiting in patients with thoracic cancer: a multicentre phase II trial

BMJ Open. 2019 Jul 4;9(7):e028056. doi: 10.1136/bmjopen-2018-028056.

Abstract

Introduction: Adding neurokinin-1 receptor antagonist (NK1RA) to 5-hydroxytryptamine-3 receptor antagonist and dexamethasone (DEX) improved carboplatin (CBDCA)-induced chemotherapy-induced nausea and vomiting (CINV) in patients with thoracic cancer. NK1RAs with high-drug cost are raising medical expenses. Olanzapine (OLZ) is less expensive and can be expected to have an excellent effect on CINV. This phase II trial aimed at evaluating the efficacy and safety of 5 mg OLZ plus granisetron (GRN) and DEX in CBDCA combination therapy with area under curve (AUC) ≥5 mg/mL/min for the prevention of nausea and vomiting in patients with thoracic cancer.

Methods and analysis: This is an open-label, single-arm, multicentre, phase II trial. Patients who receive CBDCA-based therapies (AUC ≥5) and have never been administered moderate to high emetogenic chemotherapy will be enrolled. All patients will receive a combination of GRN, DEX and OLZ. The primary endpoint is complete response (CR) rate, defined as the absence of emetic episodes and no use of rescue medication for 120 hours after the initiation of CBDCA. Forty-eight patients are required based on our hypothesis that this regimen can improve CR rate from 65% (null hypothesis) to 80% (alternative hypothesis) with a one-sided type I error of 0.1 and a power of 0.8. We set the target sample size at 50 considering dropouts.

Ethics and dissemination: The study protocol was approved by the institutional review board at each of the participating centres. Data will be presented at international conferences and published in peer-reviewed journals.

Trial registration number: UMIN000031267.

Keywords: carboplatin; nausea; olanzapine; vomiting.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiemetics / therapeutic use*
  • Antineoplastic Agents / adverse effects*
  • Carboplatin / adverse effects*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Nausea / drug therapy*
  • Olanzapine / therapeutic use*
  • Thoracic Neoplasms / drug therapy*
  • Vomiting / chemically induced
  • Vomiting / drug therapy*
  • Young Adult

Substances

  • Antiemetics
  • Antineoplastic Agents
  • Carboplatin
  • Olanzapine

Associated data

  • UMIN-CTR/UMIN000031267