Phase II Study With the Trifunctional Antibody Ertumaxomab to Treat Metastatic Breast Cancer After Progression on Trastuzumab Therapy

Phase 2

Terminated

Brief Summary: 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.

Detailed Description: 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).

Recruitment & Eligibility

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

Primary Outcome Measures

Name	Time	Method
Clinical Efficacy Measured by Objective Response Rate (Best Response During the Course of the Study)	patients are monitored for 6 months

Secondary Outcome Measures

Name	Time	Method
Duration of Response	patients are monitored for 6 months	The study was prematurely terminated, therefore no participants were analyzed
Clinical Benefit Rate	patients are monitored for 6 months	The study was prematurely terminated, therefore no participants were analyzed