Phase II Study With the Trifunctional Antibody Ertumaxomab to Treat Metastatic Breast Cancer After Progression on Trastuzumab Therapy
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
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.
研究概览
详细说明
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Key Inclusion Criteria:
- 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
Key Exclusion Criteria:
- 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
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:非随机化
- 介入模型:单组作业
- 屏蔽:无(打开标签)
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
---|---|
Clinical Efficacy Measured by Objective Response Rate (Best Response During the Course of the Study)
大体时间:patients are monitored for 6 months
|
patients are monitored for 6 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Duration of Response
大体时间:patients are monitored for 6 months
|
The study was prematurely terminated, therefore no participants were analyzed
|
patients are monitored for 6 months
|
Clinical Benefit Rate
大体时间:patients are monitored for 6 months
|
The study was prematurely terminated, therefore no participants were analyzed
|
patients are monitored for 6 months
|
合作者和调查者
调查人员
- 首席研究员:Gary Schwartz, MD、Dartmouth Hitchcock Medical Center/Norris Cotton Cancer Center; Lebanon, NH
出版物和有用的链接
一般刊物
- Ruf P, Lindhofer H. Induction of a long-lasting antitumor immunity by a trifunctional bispecific antibody. Blood. 2001 Oct 15;98(8):2526-34. doi: 10.1182/blood.v98.8.2526.
- Riesenberg R, Buchner A, Pohla H, Lindhofer H. Lysis of prostate carcinoma cells by trifunctional bispecific antibodies (alpha EpCAM x alpha CD3). J Histochem Cytochem. 2001 Jul;49(7):911-7. doi: 10.1177/002215540104900711.
- Zeidler R, Mysliwietz J, Csanady M, Walz A, Ziegler I, Schmitt B, Wollenberg B, Lindhofer H. The Fc-region of a new class of intact bispecific antibody mediates activation of accessory cells and NK cells and induces direct phagocytosis of tumour cells. Br J Cancer. 2000 Jul;83(2):261-6. doi: 10.1054/bjoc.2000.1237.
- Zeidler R, Reisbach G, Wollenberg B, Lang S, Chaubal S, Schmitt B, Lindhofer H. Simultaneous activation of T cells and accessory cells by a new class of intact bispecific antibody results in efficient tumor cell killing. J Immunol. 1999 Aug 1;163(3):1246-52.
- Kiewe P, Hasmuller S, Kahlert S, Heinrigs M, Rack B, Marme A, Korfel A, Jager M, Lindhofer H, Sommer H, Thiel E, Untch M. Phase I trial of the trifunctional anti-HER2 x anti-CD3 antibody ertumaxomab in metastatic breast cancer. Clin Cancer Res. 2006 May 15;12(10):3085-91. doi: 10.1158/1078-0432.CCR-05-2436.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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