Phase II Study of the Trifunctional Anti-HER-2/Neu x Anti-CD3 Antibody Ertumaxomab for Hormone Therapy Refractory Patients With Her-2/Neu 1+ or 2+ Expressing Advanced or Metastatic Breast Cancer
- Female gender, and if of child-bearing potential must have negative pregnancy test
result within 2 days before enrolment and must agree to practice effective birth
control during the study.
- Aged 18 years and older.
- Histologically or cytologically confirmed invasive breast cancer with stage IIIb or
IV disease with documented progression.
- Measurable disease according to RECIST.
- Histologically documented advanced primary breast cancer or biopsy of metastatic site
demonstrating HER-2/neu expression (HER-2/neu 1+ or 2+, determined by
immunohistochemistry [IHC]). HER-2/neu 2+ patients must have a negative Fluorescence
In Situ Hybridization [FISH] test result.
- Hormone receptor status Estrogen Receptors (ERs) positive and/or Progesterone
Receptors (PRs) positive.
- No prior treatment with mouse or rat antibodies.
- Life expectancy of at least six months (if the life expectancy of a patient is
unspecified she will be allowed to enter the study).
- An Eastern Cooperative Oncology Group (ECOG) performance score of £ 1.
- Patients must have had disease progression after hormonal therapy including at least
one aromatase inhibitor.
- Adequate hematological, liver and kidney function:
- Thrombocytes ³ 100000 / mm³ (= 100 x 109 /l)
- Hemoglobin ³ 10 g/dl
- Neutrophil count ³ 1500/mm³ (= 1.5 x 109 /l)
- WBC ³ 3 X 109 /l
- Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate
transaminase (SGPT) ≤ 2.5 x upper limit of normal (ULN)
- Serum bilirubin ≤ 2 x ULN
- Creatinine ≤ 1.5 x ULN or clearance ³ 60 ml/min
- No life-threatening visceral disease.
- No known brain or central nervous system metastases.
- No symptomatic pleural effusions.
- No symptomatic pericardial effusions.
- No subjects whose only site of metastatic involvement is bone metastases with the
exception of those with a measurable soft tissue component of the bone lesion seen
with imaging that does not require palliative radiation intervention and/or the
patient has a lytic bone lesion ³ 1 cm measured with radiography that can be followed
for evidence of re-calcification.
- No history of relevant cardiovascular disease:
- LVEF within the institutional ranges of normal as measured by echocardiogram or
- No prior uncontrolled or symptomatic congestive heart failure NYHA ³ 2
- No myocardial infarction within the past two years
- No uncontrolled or symptomatic cardiac arrhythmias
- No severe dyspnea.
- No pulmonary dysfunction or need for continuous supportive oxygen inhalation.
- No other concurrent uncontrolled co-morbid illness.
- No other concurrent malignancy, except treated basal cell or squamous cell carcinoma
of the skin, or in situ carcinoma of the cervix.
- Patients with documented autoimmune diseases (such as lupus) are excluded from
participation in the study unless a waiver is granted by the responsible medical
- Patients with a human immunodeficiency virus, hepatitis B or hepatitis C positive
status are excluded from participation in the study.
- No prior or concurrent chemotherapy regimen for advanced or metastatic disease.
- Prior neo-adjuvant or adjuvant chemotherapy is allowed provided it was stopped at
least six months before study entry.
- No concurrent hormone therapy (hormone therapy must be stopped at the screening
- At least 4 weeks since prior radiotherapy.
- No concurrent immune therapy.
- No concurrent corticosteroid therapy.
- No regularly used medication for a health condition or comorbidity that might result
in undue risk to the patient.
- No prior investigational treatment for advanced or metastatic disease.
- Able and willing to comply fully with the protocol.