A Phase 2 Clinical Trial:Low -Dose-bevacizumab and Pemetrexed Versus Treatment of Physician's Choice in Metastatic HER2-negative Breast Cancer Patients After Failure of Taxanes and Anthracycline-containing Regimens
试验速览
- 阶段
- 2 期
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Objective response rare (ORR)
研究概览
简要总结
This is a single-center, open, randomized, controlled phase 2 clinical trial designed to compare low-dose-bevacizumab and pemetrexed with TPC in metastatic HER2-negative breast cancer patients after failure of taxanes and anthracycline-containing regimens.
详细描述
There is no standard therapy for advanced human epidermal growth factor receptor 2 (HER2) -negative breast cancer patients after failure of taxanes and anthracycline-containing regimens at present. Pemetrexed is a multitargeted antimetabolite. Its efficacy in metastatic breast cancer has been confirmed in several small sample size studies and meta-analyses. Its response rate (RR) is about 30%, and will be higher in HER2-negative breast cancer. However, there is no study focused on this subtype of breast cancer. Bevacizumab is also an effective alternative for metastatic breast cancer. Several studies indicate that the combination of bevacizumab and chemotherapy could improve both RR and overall survival, but its use is confined by its severe side effect and far from adequate treatment. Recent years, a lot of studies have assessed the efficacy of metronomic chemotherapy. Metronomic therapy refers to the chronic administration of low doses of cytotoxic drugs at close, regular intervals. It could promote the apoptosis of tumor endothelial cell , continuously inhibit tumor angiogenesis, and exhibit a significant superiority of low toxicity, reduced cost and prolonged combination therapy period. According to reports in literature, the expression of anti-angiogenic biomarkers, such as,vascular endothelial growth factor(VEGF)-A, VEGF-C, soluble vascular endothelial growth factor receptor (sVEGFR)-1, sVEGFR-2,thrombospondin-1(TSP-1), platelet factor 4 (PF-4) might be concerned with the efficacy of metronomic therapy. Since there are no reported clinical trials according to metronomic bevacizumab in HER2-negative breast cancer, the investigators come up with this study. In this study, the investigators try to make a comparison of the efficacy and safety of low-dose-bevacizumab and pemetrexed with treatment of physician's choice (TPC) in metastatic breast cancer after failure of taxanes and anthracycline-containing regimens, to validate the correlative biomarkers and to find an optimal choice for previously treated metastatic breast cancer patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Metastatic breast cancer females confirmed by pathological and/or cytological examination;
- •Breast cancer patients who received taxanes and anthracycline-containing regimens previously;
- •HER2-negative breast cancer patients confirmed by immunohistochemical test or fluorescent in situ hybridization(FISH);
- •Patients aged from 18-70 years old, and patients with Eastern Cooperative Oncology Group（ECOG） performance status scored 0-2;
- •One or more measurable lesions in imaging examination,with a diameter no less than 20mm in ordinary computed tomography (CT) or magnetic resonance imaging (MRI), or a scanning diameter no less than 10mm in spiral CT;
- •Any other kind of concomitant chemotherapy is not allowed during the research. If the patients had accepted other chemotherapy before recruitment, he can enter into the study until the drug is eliminated 30 days later;
- •Patients without any kind of major organ dysfunction: normal blood test results, normal function of heart, liver, kidney, marrow and so on.
排除标准
- •Patients who had received any chemotherapy, radiotherapy, biotherapy, or drugs and physical treatment in other clinical trials four weeks within the enrollment;
- •Patients who has no measurable or assessable lesions ;
- •Patients with moderate or severe liver dysfunction
- •Pregnant or lactational patients;
- •Patients with severe complications, including severe heart disease, cerebrovascular disease, uncontrolled diabet and hypertension, severe infection , active peptic ulcer and so on;
- •Patient who had previously received pemetrexed-containing regimens in metastatic setting.
研究组 & 干预措施
low-dose-bevacizumab/Pemetrexed
Low-dose-bevacizumab is given at a dose of 2 mg/kg once weekly by intravenous transfusion, which is on day 1, 8 and 15, and every three weeks are a treatment cycle .Pemetrexed is given at a dose of 500mg/m2 once on the first day by intravenous transfusion, and repeated every three weeks, too. The pretreatment of pemetrexed should be conducted within the study.
干预措施: low-dose-bevacizumab/pemetrexed (Drug)
Treatment of physician' choice
Treatment of physician's choice can be any drug or regimen that has been approved in metastatic cancer at present, including monotherapy, combination therapy, target therapy and palliative therapy. It can be drugs like taxanes,capecitabine, gemcitabine, cisplatin, everolimus or even nutrient solution,et al.
干预措施: Treatment of physician's choice (Drug)
结局指标
主要结局
Objective response rare (ORR)
时间窗: up to 24 months
Evaluated as complete remission(CR) and partial remission(PR) according to Response Evaluation Criteria in Solid Tumors (RECIST)version 1.1
次要结局
- progression free survival(PFS)(up to 48 months)
- Overall survival(OS)(up to 48 months)
研究者
Li Qiao
MD
Chinese Academy of Medical Sciences