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

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, there have been no reports of a randomized controlled clinical trial of apatinib combined with vinorelbine for the treatment of triple-negative breast cancer (TNBC). 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 238 female patients with locally recurrent or metastatic TNBC, admitted to the Liaoning Cancer Hospital & Institute, Northeast China. All enrolled patients will be randomized to oral vinorelbine alone (40 mg, thrice a week (Mondays, Wednesdays, and Fridays) in each 3-week cycle), or in combination with oral apatinib mesylate (500 mg, once daily in each 3-week cycle). Radiographic assessment will be performed every 6 weeks for 36 weeks and every 9 weeks thereafter. The primary outcome is 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 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 patients with TNBC, who have been treated with anthracyclines and taxanes, in Northeast China. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03932526. Registered on 30 April 2019.