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

Metastatic Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00522457
• Other study ID #: IV-ERT-BC-04
• Status: Terminated
• Phase: Phase 2
• First received: August 28, 2007
• Last updated: April 28, 2011
• Start date: January 2008
• Est. completion date: December 2009

Study information

• Verified date: April 2011
• Source: Neovii Biotech
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• ertumaxomab
Ertumaxomab will be intravenously administered to see if it can increase the patient's objective response rate.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Neovii Biotech	Fresenius Biotech North America

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (5)

Kiewe P, Hasmüller S, Kahlert S, Heinrigs M, Rack B, Marmé A, Korfel A, Jäger 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. — View 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. — View 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. — View Citation

Zeidler R, Mysliwietz J, Csánady 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Efficacy Measured by Objective Response Rate (Best Response During the Course of the Study)		patients are monitored for 6 months	No
Secondary	Duration of Response	The study was prematurely terminated, therefore no participants were analyzed	patients are monitored for 6 months	No
Secondary	Clinical Benefit Rate	The study was prematurely terminated, therefore no participants were analyzed	patients are monitored for 6 months	No

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