Phase II Study With the Trifunctional Antibody Ertumaxomab to Treat Metastatic Breast Cancer Progressing After Endocrine Treatment

Study Overview
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Brief Summary
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The purpose of the study is to demonstrate clinical efficacy of the investigational trifunctional bispecific antibody ertumaxomab for treatment of patients with HER-2/neu 1+ or 2+ (FISH-) expressing advanced or metastatic breast cancer (stage III b/IV) which has progressed after endocrine therapy. Ertumaxomab is a trifunctional bispecific antibody targeting Her-2/neu 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 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
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An open-label, non-randomized, uncontrolled, one-stage, phase II study evaluating the efficacy and safety of the investigational trifunctional bispecific antibody ertumaxomab (anti-Her-2/neu x anti-CD3) for the treatment of hormone therapy refractory advanced or metastatic breast cancer tumours (stage IIIb or IV) which are known to express HER-2/neu (1+ or 2+/FISH negative).Ertumaxomab will be administered at 7 day intervals by constant rate 3 hour intravenous (i.v.) infusions according to the following sequential dose schedule: 10 µg (day 0) and thereafter 100 µg flat doses once every 7 days (± 1 day) for a maximum of up to 12 weeks or until disease progression or any other unacceptable toxicity.

Official Title
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Phase II Study for Repeated Dosing of the Trifunctional Bispecific Anti-HER-2/Neu x Anti-CD3 Antibody Ertumaxomab in Patients With HER-2/Neu 1+ or 2+/FISH Negative Expressing Advanced or Metastatic Breast Cancer (Stage IIIb/IV) Progressing After Endocrine Treatment

Conditions
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Metastatic Breast Cancer, Advanced Breast Cancer

Intervention / Treatment
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* Biological: ertumaxomab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent form Women ≥ 18 years, negative pregnancy test at screening life expectancy of at least 6 months Locally advanced (stage IIIb) or 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/neu expression 1+ or 2+ / FISH negative Estrogen Receptors (ERs) and/or Progesterone Receptors (PRs) positive Prior adequate endocrine therapy for advanced or metastatic disease Disease progression during or after endocrine therapy No prior treatment with mouse or rat antibodies ECOG performance score of ≤ 1 Adequate hematological, liver and kidney function Exclusion Criteria: Women who are pregnant or breast-feeding Known HIV infection or Presence of autoimmune disease or other Concurrent non-malignant co-morbidities that are uncontrolled History or symptoms indicative of brain or CNS 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) Documented acute or chronic infection requiring antibiotic treatment Any concurrent chemo-, hormonal, immuno- or corticoid therapy Any prior chemotherapy for advanced or metastatic disease Any concurrent investigational treatment for advanced or metastatic disease History of relevant cardiovascular disease as follows: Left ventricular ejection fraction (LVEF) below the institution's lower limit of normal, based on echocardiography (ECG) at rest Uncontrolled or symptomatic congestive heart failure (New York Heart Association (NYHA) > 2 Uncontrolled or symptomatic arrhythmia and/or angina pectoris Myocardial infarction during the last 2 years

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: ertumaxomab|10 µg, IV on day 0 followed by 100 µg every 7 days up to a maximum of 12 infusions.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical efficacy measured by objective response rate (best response during the course of the study) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: |  |  | 
| Clinical benefit rate |  |  | 
| Duration of response |  |  | 
| Time to progression (TTP) |  |  | 
| Safety: |  |  | 
| Incidence of adverse events (AEs) |  |  | 
| Presence of human anti-murine antibodies after ertumaxomab infusion |  |  | 
| Vital signs |  |  | 
| Laboratory parameters |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, investigational drug, drug therapy, Antineoplastic Protocols, Immunotherapy, Metastatic breast cancer, Advanced breast cancer, Stage III to IV breast cancer, Hormonal therapy refractory, Failure of hormonal therapy, Her-2/neu expressing breast cancer, Her-2/neu