Phase II Study With the Trifunctional Antibody Ertumaxomab to Treat Metastatic Breast Cancer After Progression on Trastuzumab Therapy
Condition: Metastatic Breast Cancer; Advanced Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: ertumaxomab
Intervention description: Ertumaxomab will be intravenously administered to see if it can increase the patient's objective response rate.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast Cancer; investigational drug; drug therapy; Antineoplastic Protocols; Immunotherapy; Metastatic breast cancer; Advanced breast cancer; Stage IV breast cancer; Her-2/neu expressing breast cancer; Her-2/neu; Trastuzumab refractory

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.
    

Eligibility criteria:

        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