Phase II Study Of The Trifunctional Bispecific Anti-HER-2/Neu x Anti-CD3 Antibody Ertumaxomab In Patients With HER-2/Neu Overexpressing (3+ Or 2+/FISH+) Metastatic Breast Cancer Progressing After Trastuzumab Treatment
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 19
- 试验地点
- 5
- 主要终点
- Clinical Efficacy Measured by Objective Response Rate (Best Response During the Course of the Study)
研究概览
简要总结
This study has the purpose to demonstrate clinical efficacy of the investigational new drug ertumaxomab in patients with human epidermal growth factor receptor-2 (HER-2/neu) overexpressing (3+ or 2+ with a positive Fluorescence In Situ Hybridization (FISH) test result) metastatic breast cancer progressing after trastuzumab treatment.
Ertumaxomab is a trifunctional bispecific antibody targeting Her-2/neu on tumor cells and CD3 on T cells. Trifunctional antibodies represent a new concept for targeted anticancer therapy. This new antibody class has the capability to redirect T cells and accessory immune effector cells (e.g. macrophages, dendritic cells [DCs] and natural killer [NK] cells) to the tumor site. According to preclinical data, trifunctional antibodies activate these immune cells, which can trigger a complex anti-tumor immune response.
详细描述
This study is an open-label, non-randomized, uncontrolled, two-stage phase II study evaluating the efficacy and safety of ertumaxomab. Ertumaxomab will be administered three times at 7 day intervals by constant rate 3 hour intravenous (i.v.) infusions according to the following dose schedule: 10 µg (day 0); 100 µg (day 7 ± 1 day) and 100 µg (day 14 ± 1 day) (flat doses).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Women ≥ 18 years, Negative pregnancy test at screening and life expectancy of at least 3 months
- •metastatic (stage IV) and not curable adenocarcinoma of the breast
- •Measurable disease, defined as at least one lesion that is measurable in one dimension (RECIST)
- •HER-2 overexpression 3+ or 2+ FISH positive
- •Patients must have received one prior therapy with trastuzumab as last treatment before entry into the study. If trastuzumab was given as single agent treatment, patients must have received prior chemotherapy for metastatic disease
- •Trastuzumab has been discontinued before study entry
- •disease had progressed during or after trastuzumab therapy
- •Eastern Cooperative Oncology Group (ECOG)performance score of ≤ 2
- •Adequate hematological, liver and kidney function
排除标准
- •Women who are pregnant or breast feeding
- •Any history or symptoms indicative of brain or central nervous system metastases
- •Prior diagnosis of any malignancy not cured by surgery alone less than 5 years before study entry (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin)
- •Human anti-murine antibody positive or hypersensitivity to murine proteins and any other component of the study drug
- •Known autoimmune diseases, Human immunodeficiency virus (HIV), hepatitis B or C infection as well as other acute or chronic infection or other concurrent non-malignant co-morbidities that are uncontrolled
- •Any concurrent chemotherapy, hormonal therapy, immunotherapy or corticoid therapy
- •Concurrent antibiotic treatment
- •Any concurrent investigational treatment for metastatic disease
- •Cardiovascular exclusion criteria:
- •Unstable or uncontrolled pectorial angina
- •Myocardial infarction during the last 6 months
- •Valvular heart disease that requires treatment
- •Cardiomyopathy (congestive, hypertrophic or restrictive)
- •Acute myocarditis
- •Congestive heart failure (CHF): dyspnea, clinically or radiologically diagnosed
- •Left ventricular ejection fraction (LVEF)outside institution's normal range based on echocardiography at rest
- •Left ventricular diameter > 56 mm based on M-mode echocardiography at rest
- •Arrhythmias that require treatment (atrioventricular block II/III degree, atrial fibrillation, ventricular tachycardia)
- •Poorly or uncontrolled hypertension, asthma, seizures, allergies, pulmonary dysfunction
结局指标
主要结局
Clinical Efficacy Measured by Objective Response Rate (Best Response During the Course of the Study)
时间窗: patients are monitored for 6 months
次要结局
- Duration of Response(patients are monitored for 6 months)
- Clinical Benefit Rate(patients are monitored for 6 months)