A Phase II Single-arm Clinical Trial of Inetetamab Combined With Pyrotinib and Chemotherapy in the Treatment of HER2 Positive Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 71
- 试验地点
- 1
- 主要终点
- Objective Response Rate，ORR
研究概览
简要总结
HER2-targeted therapy after the failure of trastuzumab treatment has become a new difficulty and challenge. Inetetamab, a new antibody to optimize the ADCC effect, has become one of the second-line treatment options after trastuzumab fails, showing good survival benefits. Pyrotinib, another second-line HER2 targeted drug, is a typical representative of TKI drugs, which not only has a strong HER2 antagonistic effect but also can synergize with monoclonal antibodies to amplify the ADCC effect. Pyrotinib and Inetetamab showed excellent anti-tumor efficacy and good safety in TKI and optimized ADCC respectively. we plan to carry out a phase II single-arm clinical study to evaluate the efficacy and safety of "Inetetamab combined with Pyrotinib and chemotherapy" in the treatment of her positive metastatic breast cancer.
详细描述
Trastuzumab is the first target drug for HER2 positive metastatic breast cancer, which can significantly improve the survival of patients with HER2 positive metastatic breast cancer and become the first-line standard treatment. However, the selection of second-line targeted drugs after the failure of trastuzumab treatment has become a new difficulty and challenge. Studies have shown that the ADCC effect is one of the main mechanisms of the anti-tumor effect of trastuzumab. Therefore, Inetetamab, a new antibody to optimize the ADCC effect, has become one of the second-line treatment options after trastuzumab fails, showing good survival benefits. Pyrotinib, another second-line HER2 targeted drug, is a typical representative of TKI drugs, which not only has a strong HER2 antagonistic effect but also can synergize with monoclonal antibodies to amplify the ADCC effect. As two important class 1.1 innovative drugs in China, Pyrotinib and Inetetamab showed excellent anti-tumor efficacy and good safety in TKI and optimized ADCC respectively. Considering that the current guidelines recommend the combination of multiple anti-HER2 targeted drugs, and basic research also shows that Pyrotinib and Inetetamab have a synergistic effect, we plan to carry out a phase II single-arm clinical study to evaluate the efficacy and safety of "Inetetamab combined with Pyrotinib and chemotherapy" in the treatment of her positive metastatic breast cancer, so as to provide better results for patients with HER2 positive metastatic breast cancer Treatment options!
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 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Subjects must meet all of the following conditions:
- •Adult female patients (age 18-70 years) with metastatic breast cancer confirmed by pathology or imaging;
- •Pathological diagnosis of HER-2 was positive (definition: immunohistochemical results were + + + or in situ hybridization results were positive);
- •Received trastuzumab treatment in the past;
- •the patients have received 1-3 treatments for metastatic breast cancer in the past;
- •According to RECIST 1.1, patients with at least one target lesion or simple bone metastasis can be evaluated;
- •ECoG score of physical status was less than 2, and the expected survival time was not less than 3 months;
- •Prior treatment-related toxicity should be reduced to NCI CTCAE (version 5.0) ≤ 1 degree (except for hair loss or other toxicity which is considered as no risk to patient's safety according to the investigator's judgment) 8）LVEF≥50%；
- •Sufficient functional reserve of bone marrow
- •White blood cell count (WBC) ≥ 3.0 × 10 ^ 9 / L,
- •Neutrophil count (ANC) ≥ 1.5 × 10 ^ 9 / L,
- •Platelet count (PLT) ≥ 100 × 10 ^ 9 / L 10) Previous treatment-related toxicity should be relieved as NCI CTCAE (version 5.0) ≤ 1 degree, total bilirubin (TBIL) ≤ 1.5 × upper limit of normal value (ULN), alanine aminotransferase (ALT / AST) ≤ 2.5 × ULN (liver metastasis patients ≤ 5xuln), serum creatinine ≤ 1.5 × ULN or creatinine clearance rate (CCR) ≥ 60 ml / min; 11) Be able to understand the research process, volunteer to participate in the study, and sign informed consent.
排除标准
- •Subjects were not allowed to participate in the study if they had any of the following conditions:
- •No trastuzumab treatment was received;
- •Have received more than 3 therapeutic regimens for metastatic breast cancer;
- •No treatment for metastatic breast cancer was received;
- •Patients who are known to be allergic to active or other components of the study drug.
- •They received radiotherapy, chemotherapy, endocrine therapy within 4 weeks before enrollment, or were participating in any clinical trials of intervention drugs;
- •Pregnant or lactating women, women of childbearing age who refused to take effective contraceptive measures during the study period.
- •Any other situation in which the researcher considers that the patient is not suitable for the study may interfere with the concomitant diseases or conditions involved in the study, or there are any serious medical barriers that may affect the safety of the subjects (e.g., uncontrollable heart disease, hypertension, active or uncontrollable infection, active hepatitis B virus infection)
研究组 & 干预措施
Inetetamab Combined With Pyrotinib and Chemotherapy
Inetetamab: 8mg/kg for the first dose, 6mg/kg for the following doses, every 3 weeks for one cycle.
Pyrotinib: 400mg, oral, every day.
Chemotherapy: the choice of physicians，as the following regimens:
Capecitabine, 1000 mg/m2, d1-d14, 3-week cycle Gemcitabine, 1000 mg/m2, D1, D8, 3-week cycle Vinorelbine, 25-30 mg/m2, D1, D8, 3-week cycle Carboplatin, AUC = 6, 3-week cycle Albumin paclitaxel, 100 mg/m2, weekly Eribulin, 1.4 mg/m2, D1, D8, 3-week cycle
干预措施: Inetetamab (Drug)
Inetetamab Combined With Pyrotinib and Chemotherapy
Inetetamab: 8mg/kg for the first dose, 6mg/kg for the following doses, every 3 weeks for one cycle.
Pyrotinib: 400mg, oral, every day.
Chemotherapy: the choice of physicians，as the following regimens:
Capecitabine, 1000 mg/m2, d1-d14, 3-week cycle Gemcitabine, 1000 mg/m2, D1, D8, 3-week cycle Vinorelbine, 25-30 mg/m2, D1, D8, 3-week cycle Carboplatin, AUC = 6, 3-week cycle Albumin paclitaxel, 100 mg/m2, weekly Eribulin, 1.4 mg/m2, D1, D8, 3-week cycle
干预措施: Pyrotinib (Drug)
Inetetamab Combined With Pyrotinib and Chemotherapy
Inetetamab: 8mg/kg for the first dose, 6mg/kg for the following doses, every 3 weeks for one cycle.
Pyrotinib: 400mg, oral, every day.
Chemotherapy: the choice of physicians，as the following regimens:
Capecitabine, 1000 mg/m2, d1-d14, 3-week cycle Gemcitabine, 1000 mg/m2, D1, D8, 3-week cycle Vinorelbine, 25-30 mg/m2, D1, D8, 3-week cycle Carboplatin, AUC = 6, 3-week cycle Albumin paclitaxel, 100 mg/m2, weekly Eribulin, 1.4 mg/m2, D1, D8, 3-week cycle
干预措施: Capecitabine (Drug)
Inetetamab Combined With Pyrotinib and Chemotherapy
Inetetamab: 8mg/kg for the first dose, 6mg/kg for the following doses, every 3 weeks for one cycle.
Pyrotinib: 400mg, oral, every day.
Chemotherapy: the choice of physicians，as the following regimens:
Capecitabine, 1000 mg/m2, d1-d14, 3-week cycle Gemcitabine, 1000 mg/m2, D1, D8, 3-week cycle Vinorelbine, 25-30 mg/m2, D1, D8, 3-week cycle Carboplatin, AUC = 6, 3-week cycle Albumin paclitaxel, 100 mg/m2, weekly Eribulin, 1.4 mg/m2, D1, D8, 3-week cycle
干预措施: Gemcitabine (Drug)
Inetetamab Combined With Pyrotinib and Chemotherapy
Inetetamab: 8mg/kg for the first dose, 6mg/kg for the following doses, every 3 weeks for one cycle.
Pyrotinib: 400mg, oral, every day.
Chemotherapy: the choice of physicians，as the following regimens:
Capecitabine, 1000 mg/m2, d1-d14, 3-week cycle Gemcitabine, 1000 mg/m2, D1, D8, 3-week cycle Vinorelbine, 25-30 mg/m2, D1, D8, 3-week cycle Carboplatin, AUC = 6, 3-week cycle Albumin paclitaxel, 100 mg/m2, weekly Eribulin, 1.4 mg/m2, D1, D8, 3-week cycle
干预措施: Vinorelbine (Drug)
Inetetamab Combined With Pyrotinib and Chemotherapy
Inetetamab: 8mg/kg for the first dose, 6mg/kg for the following doses, every 3 weeks for one cycle.
Pyrotinib: 400mg, oral, every day.
Chemotherapy: the choice of physicians，as the following regimens:
Capecitabine, 1000 mg/m2, d1-d14, 3-week cycle Gemcitabine, 1000 mg/m2, D1, D8, 3-week cycle Vinorelbine, 25-30 mg/m2, D1, D8, 3-week cycle Carboplatin, AUC = 6, 3-week cycle Albumin paclitaxel, 100 mg/m2, weekly Eribulin, 1.4 mg/m2, D1, D8, 3-week cycle
干预措施: Carboplatin (Drug)
Inetetamab Combined With Pyrotinib and Chemotherapy
Inetetamab: 8mg/kg for the first dose, 6mg/kg for the following doses, every 3 weeks for one cycle.
Pyrotinib: 400mg, oral, every day.
Chemotherapy: the choice of physicians，as the following regimens:
Capecitabine, 1000 mg/m2, d1-d14, 3-week cycle Gemcitabine, 1000 mg/m2, D1, D8, 3-week cycle Vinorelbine, 25-30 mg/m2, D1, D8, 3-week cycle Carboplatin, AUC = 6, 3-week cycle Albumin paclitaxel, 100 mg/m2, weekly Eribulin, 1.4 mg/m2, D1, D8, 3-week cycle
干预措施: Albumin paclitaxel (Drug)
Inetetamab Combined With Pyrotinib and Chemotherapy
Inetetamab: 8mg/kg for the first dose, 6mg/kg for the following doses, every 3 weeks for one cycle.
Pyrotinib: 400mg, oral, every day.
Chemotherapy: the choice of physicians，as the following regimens:
Capecitabine, 1000 mg/m2, d1-d14, 3-week cycle Gemcitabine, 1000 mg/m2, D1, D8, 3-week cycle Vinorelbine, 25-30 mg/m2, D1, D8, 3-week cycle Carboplatin, AUC = 6, 3-week cycle Albumin paclitaxel, 100 mg/m2, weekly Eribulin, 1.4 mg/m2, D1, D8, 3-week cycle
干预措施: Eribulin (Drug)
结局指标
主要结局
Objective Response Rate，ORR
时间窗: 18 weeks after enrollment
Objective response rate assessed at 18 weeks after enrollment，that is about 6 cycles of treatment
次要结局
- Progression Free Survival，PFS(2 years)
- the rate of adverse events(up to 24 weeks after enrollment)
- overall survival，OS(4 years)
- Clinical Benefit Rate，CBR(24 weeks after enrollment)
- Quality of life scale score，QoL(1 year)
- Exploration of biomarkers(the first week after the enrollment)
研究者
Jianli Zhao
Attending Doctor
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University