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

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, 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.

Keywords: Advanced breast cancer; Apatinib; Metastatic; Triple-negative breast cancer; Vinorelbine.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1

Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT). Timepoint (t): -t1: baseline evaluations (conducted within 2 weeks of the start of protocol therapy); t0: random allocation; t1: during treatment (evaluations will be conducted every 6 weeks (two cycles)); t2: patients will be monitored for new or existing AEs at 4 weeks after treatment discontinuation; t3: follow up for survival will be monitored every 3 months after treatment discontinuation until patient death or study completion. *Eligible patients will be randomly assigned to receive either oral vinorelbine plus placebo (control group) or oral vinorelbine combined with apatinib mesylate (experimental group). a Concomitant medication includes opioid analgesics and new anticancer treatment. b Laboratory examinations include hematology (hemoglobin, white blood cell count, neutrophil count, and platelet count); blood biochemical tests (total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, serum creatinine, total protein, Na+, K+, Mg2+, Cl−, Ca2+, urea, and pregnancy test (if applicable); and tumor marker detection (breast cancer-associated antigen CA153 and carcinoembryonic antigen). ECOG PS, Eastern Cooperative Oncology Group performance status; EORTC QLQ-C30, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30

Fig. 2

Schedule of enrollment, interventions, and assessments. ECOG PS, Eastern Cooperative Oncology Group performance status; EORTC QLQ-C30, version 3, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30; CT, computed tomography; MRI, magnetic resonance imaging