An Open Labelled, Multicenter-phase II Study of Chiauranib Combine With Capecitabine in Advanced Triple-negative Breast Cancer Failed to Prior Anthracyclines and Taxanes Therapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 9
- 试验地点
- 4
- 主要终点
- ORR(Objective reponse rate)
研究概览
简要总结
This study is to evaluate the preliminary efficacy and safety of chiauranib in combine with capecitabine in advanced triple-negative breast cancer failed to prior anthracyclines and taxanes therapy
详细描述
Chiauranib is a novel orally active multi-target inhibitor that simultaneously inhibits the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3,PDGFRa and c-Kit), mitosis-related kinase Aurora B and chronic inflammationrelated kinase CSF-1R in a high potency manner with the IC50 at a single-digit nanomolar range. In particular, Chiauranib showed very high selectivity in the kinase inhibition profile with little activity on off-target nonreceptor kinases, proteins, GPCR and ion channels, indicative of a better drug safety profile in terms of clinical relevance.
This study including two phases: (1) dose-escalation , this phase using a 3+3design，9-18 patients will be enrolled and receive 25mg/35mg/50mg chiauranib and 1000mg/m2 capecitabine Q3W. (2) dose-expansion，About 20 patients will be enrolled and receive the MTD dose of chiauranib and 1000mg/m2 capecitabine Q3W.
This study also to explore the PK variation and gene expression via blood samples
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •All patients must have given signed, informed consent prior to registration on study
- •age ≥ 18 years
- •Histological or cytological evidence of estrogen-receptor negative (ER-), progesterone receptor negative (PgR-) and human epidermal growth factor-2 receptor negative (HER2-) Breast Cancer by local laboratory testing.
- •Patients with locally advanced inoperable or recurrent/metastatic TNBC and had failed treatment with anthracyclines and taxanes.
- •At least 1 lesion can be accurately measured, as defined by RECIST1.1
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •Laboratory criteria are as follows:
- •Complete blood count: hemoglobin (Hb) ≥90g/L ; absolute neutrophil count (ANC) ≥1.5×109/L ; platelets ≥90×109/L; 2) Biochemistry test: serum creatinine(cr) <1.5×ULN; total bilirubin<1.5×ULN; alanine aminotransferase(ALT) ,aspartateaminotransferase(AST)≤2.5×ULN; (ALT,AST#5×ULN if liver involved) 3) Coagulation test: International Normalized Ratio (INR) < 1.5
- •Life expectancy of at least 3 months
排除标准
- •Patients have used any anti-cancer therapy, including adiotherapy, chemotherapy, immunotherapy, target therapy, and other anti-tumor treatments within 28 days before the first dose
- •Patients received vascular endothelial growth factor(VEGF)/vascular endothelial growth factor receptor(VEGFR) inhibitor, like Apatinib, Anlotinib, Fruquintinib, Bevacizumab, etc., or Aurora kinase inhibitors, etc; Patients had treatment of capecitabine (except who received the treatment of capecitabine in Neoadjuvant/ Adjuvant therapy, and Recurrence occurs after 12 months)
- •Has known allegies to Chiauranib, capecitabine or any of the excipients
- •prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer
- •Treatment with an investigational agent/instrument within 28 days prior to first dose of study drug
- •Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1
- •Patients with prior invasive malignancies in the past five years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ
- •History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis
- •Have uncontrolled or significant cardiovascular disease, including:
- •Congestive heart failure, unstable angina pectoris, myocardial infarction within 6 months prior to study entry; arrhythmia, or Left Ventricular Ejection Fraction (LVEF) < 50% requiring treatment with agents during screening stage 2) primary cardiomyopathy(dilated cardiomyopathy, hypertrophic cardiomyocyte, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, et,al) 3) History of significant QT interval prolongation, or Corrected QT Interval (QTc) > 470 ms prior to study entry 4) Symptomatic coronary heart disease requiring treatment with agents 5) History of hypertension treated by≥2 agents, or the Blood pressure(Bp) ≥140/90 mmHg prior to study entry 6) Other condition investigator considered inappropriate
- •CT or MRI of the chest during the screening period shows interstitial lung disease or pulmonary fibrosis or lung inflammation that requires treatment, or within 6 months before the first dose, history of pneumonia requiring oral or intravenous steroid treatment
- •Have clinical significant gastrointestinal abnormality that would impair the ingestion, transportation or absorption of oral agents, history of gastrointestinal perforation or abdominal fistula, peptic ulcer disease within 6 months prior to first dose of study drug
- •Urinary protein ≥ 2+ and quantitative urinary protein ≥ 1g/24 h during the screening period
- •History of active bleeding within the past 2 months, patients with bleeding potential during the screening period, or receiving anticoagulation therapy
- •Pleural fluid, ascites or pericardial effusion with significant symptoms or required treatment of puncture or drainage during the screening period
- •History of deep venous thrombosis or Pulmonary embolism within the past 6 months
- •Active infection requiring oral or intravenous systemic antimicrobial therapy during the screening period
- •Screening for HIV antibody positive
- •Screening test for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive with virus replication, hepatitis C antibody (HCVAb) positive with virus replication
- •Any mental or cognitive disorder, that would impair the ability to understand the informed consent document, or the compliance of study
- •Candidates with drug and alcohol abuse
- •Participants of reproductive potential not willing to use adequate contraceptive measures for the duration of the study.Pregnant or breastfeeding women
- •Any other condition which is inappropriate for the study in the opinion of the investigators
研究组 & 干预措施
Experimental: Chiauranib + capecitabine
Patients receive the combined treatment of Chiauranib plus capecitabine, 21 days as a cycle until objective disease progression.
干预措施: Chiauranib (Drug)
Experimental: Chiauranib + capecitabine
Patients receive the combined treatment of Chiauranib plus capecitabine, 21 days as a cycle until objective disease progression.
干预措施: capecitabine (Drug)
结局指标
主要结局
ORR(Objective reponse rate)
时间窗: 2years
Overall response rate (ORR) is defined as the percentage of patients with complete or partial response evaluated by RECIST 1.1. Per RECIST 1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
次要结局
- DoR (Duration of response)(2years)
- PFS (Progression-free survival)(2years)
- CBR (Clinical Benefit Rate)(2years)
- OS(Overall survival)(2years)
- AEs(2years)