Combined Use of Apatinib Mesylate and Vinorelbine Versus Single Use of Vinorelbine in Triple-negative Breast Cancer

Study Overview
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Brief Summary
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To compare the therapeutic effect of vinorelbine used alone or combined with apatinib mesylate for recurrent or metastatic TNBC patients who have at least received one chemotherapy regimen, including anthracyclines and taxanes, providing clinical evidence for multi-line treatment options for advanced TNBC.

Detailed Description
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The emergence of new molecular targeted drugs provides new prospects for the treatment of advanced breast cancer; and its future therapeutic trend includes chemotherapy combined with molecular targeted therapy. Apatinib mesylate (Aitan), a novel small molecule anti-angiogenic agent, highly selectively inhibits the activity of vascular endothelial growth factor receptor-2 tyrosine kinase. Aitan also blocks the signaling of vascular endothelial growth factor binding to its receptor, thereby strongly inhibiting tumor angiogenesis and exerting anti-tumor effect.However, a randomized controlled clinical trial of apatinib combined with vinorelbine for TNBC has not been reported. The objective of this study is to compare the therapeutic effect of vinorelbine alone or combined with apatinib mesylate for recurrent or metastatic triple-negative breast cancer (TNBC) patients who have received at least two regimens containing anthracyclines and taxanes.

Official Title
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Combined Use of Apatinib Mesylate and Vinorelbine Versus Single Use of Vinorelbine in Recurrent or Metastatic Triple-negative Breast Cancer: a Double-blinded Randomized Controlled Clinical Trial

Conditions
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Triple-negative Breast Cancer

Intervention / Treatment
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* Drug: Vinorelbine + placebo
* Drug: Vinorelbine + Apatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients with recurrent or metastatic TNBC, as confirmed by histological or cytological examination Age 18-70 years old According to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, there is at least one measurable lesion. The Eastern Cooperative Oncology Group (ECOG) scores 0-2 Expected survival ≥ 12 weeks Negative for ER/PR All patients will be tested for bone marrow capacity, liver and renal functions within 7 days prior to enrollment Previous use of anthracyclines and/or taxanes The medication history of vinorelbine Female patients of childbearing age must take adequate contraception; otherwise the patients must be proven to be infertile No history of serious heart, lung, liver, and kidney diseases Provision of written informed consent Exclusion Criteria: Patients who receive chemotherapy, radiation therapy, targeted drugs, or hormone therapy within 3 weeks of administration Patients using corticosteroids for untreated brain or subdural metastatic lesions, need to have stopped it, at least for 4 weeks or until there are no signs of brain metastasis and/or symptoms must have stabilized for at least 4 weeks, if local treatment has been completed. Enhanced computed tomography (CT) or magnetic resonance imaging (MRI) images during screening are compared with those performed at least 4 weeks earlier to determine radiological stability. Patients with severe vascular diseases, including unstable angina, myocardial infarction, or severe arrhythmia in the past 6 months History of HIV infection or active chronic hepatitis B or C Patients with other serious infectious diseases Patients positive for ER/PR/HER-2 positive Patients with allogeneic organ transplants requiring immunosuppressive therapy History of other malignant tumors within 5 years, except for cured cervical carcinoma in situ or basal cell carcinoma of the skin Other destabilizing factors that may interfere with patients or have an impact on the trial results Allergic to target drugs or allergic to related drugs applied in the trial Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vinorelbine + placebo group<br>92 enrolled patients will be assigned to receive oral vinorelbine plus placebo until disease progression or other criteria for administration termination. | Drug: Vinorelbine + placebo<br>* Combined administration of vinorelbine and placebo. Based on oral administration of vinorelbine, the patients will be given oral placebo (starch as an ingredient). The placebo appearance, including shape, size, color and weight, taste, labeling and packing are the same with those of apatinib mesylate tablets.<br>* Other names: AiTan+ placebo;|
| Experimental: Vinorelbine + Apatinib group<br>92 enrolled patients will be assigned to receive oral patatinib mesylate in combination with vinorelbine until disease progression or other criteria for administration termination. | Drug: Vinorelbine + Apatinib<br>* Combined administration of vinorelbine and apatinib. Vinorelbine tartrate soft capsule (also named Navelbine; registration No. H20140657; Pierre Fabre Medicament, Boulogne, France) 40 mg once orally, taken in the morning (at least 1 hour before or at least 1 hour after meals), three times a week (Mondays, Wednesdays, and Fridays), for a continuous 21-day cycle. Apatinib mesylate tablets (also named Aitan, State Medical Permission No. H20140103; Jiangsu Hengrui Pharmaceutical Co., Ltd., China), 500 mg orally, taken once a day for a continuous 21-day cycle.<br>* Other names: Navelbine+AiTan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress-Free Survival(PFS) | PFS refers to the length of time from random enrollment to any recorded tumor progression or death from any cause. | Day 1 of treatment until disease progression or death from any cause, assessed up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | OS indicates the length of time from enrollment to death from any cause.When no information on death is collected in the clinical database, the last date when the patient is still known to have survived is used as the cut-off point. | Up to 24 months | 
| Disease control rate (DCR) | DCR indicates the percentage of patients with CR, partial remission, and disease stabilization; and maintenance over 4 weeks, accounts for all the subjects with evaluable efficacy. | Up to 24 months | 
| Overall remission rate (ORR) | ORR is the proportion of patients who achieve a complete or partial response ((CR+PR)/total number of cases x 100%), as assessed by the RECIST v1.1. | Up to 24 months | 
| Adverse events at levels 3 and 4 | Patients with adverse events at levels 3 and 4 will be assessed according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 4.0. | every 6 weeks (two cycles) and 4 weeks after treatment discontinuation |