Clinical trial NCT00522457: Phase II Study With the Trifunctional Antibody Ertumaxomab to Treat Metastatic Breast Cancer After Progression on Trastuzumab Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Advanced Breast Cancer
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
Lead sponsor: Neovii Biotech
Sponsor class: INDUSTRY
Collaborators: name: Fresenius Biotech North America
First posted: 2007-08-29
Enrollment: 19
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Clinical Efficacy Measured by Objective Response Rate (Best Response During the Course of the Study)
timeFrame: patients are monitored for 6 months
Secondary outcomes:
measure: Duration of Response
timeFrame: patients are monitored for 6 months
measure: Clinical Benefit Rate
timeFrame: patients are monitored for 6 months
Other outcomes:
Locations:
city: Minneapolis
country: United States
state: Minnesota
city: Lebanon
country: United States
state: New Hampshire
city: New York
country: United States
state: New York
city: Ottawa
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
Study officials:
affiliation: Dartmouth Hitchcock Medical Center/Norris Cotton Cancer Center; Lebanon, NH
name: Gary Schwartz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.