Combined use of apatinib mesylate  and vinorelbine versus  single use of vinorelbine in recurrent or metastatic  triple-negative breast cancer: study protocol for a randomized controlled clinical trial

Abstract

Background: The emergence of new molecular targeted drugs provides new prospects for the treatment of advanced breast cancer; the future therapeutic trend includes chemotherapy combined with molecular targeted therapy. Apatinib mesylate, a novel, small anti-angiogenic agent, highly selectively inhibits the activity of vascular endothelial growth factor receptor-2 tyrosine kinase. Apatinib mesylate also blocks the signaling of vascular endothelial growth factor binding to its receptor, thereby, strongly inhibiting tumor angiogenesis and exerting an anti-tumor effect. However, a randomized controlled clinical trial of apatinib combined with vinorelbine for triple-negative breast cancer (TNBC) has not been reported. We will compare the therapeutic effect of vinorelbine alone or in combination with apatinib mesylate in patients with recurrent or metastatic TNBC in North China who have received at least two drug treatments including anthracyclines and taxanes. Methods/analysis: This study is a triple-blind, randomized, placebo-controlled, parallel-group clinical trial. We plan to include 164 female patients with locally recurrent or metastatic TNBC and without BRCA1 mutation (as BRCA -positive patients would have poor responses to the therapeutic methods designed in this study), admitted at the Liaoning Cancer Hospital & Institute, Northeast China. All enrolled patients will be randomized to orally take vinorelbine alone (40 mg orally, thrice a week (Mondays, Wednesdays, and Fridays) in each 3-week cycle) or combined with apatinib mesylate (500 mg orally, once daily of each 3-week cycle). Radiographic assessment will be performed every 6 weeks for 36 weeks, and every 9 weeks thereafter. The primary outcome is measurement of progression-free survival and secondary outcomes include overall survival, disease control rate, objective response rate, and incidence of adverse events at grades 3 and 4 as defined by the National Cancer Institute Common Toxicity Criteria [NCI-CTC] Version 4.0. Outcome measures will be evaluated at baseline (< 2 weeks before starting treatment), every 6 weeks during treatment, and at 4 weeks and every 3 months after treatment discontinuation. Discussion: Based on the data from this trial, we hope to identify a treatment plan that is suitable for female TNBC patients in Northeast China who have been treated with anthracyclines and taxanes. Trial registration: ClinicalTrials.gov (identifier: NCT03932526). Registered on April 30, 2019.