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

NCT00452140 | Terminated Phase 2 DMC

• 2 other identifiers: IV-ERT-BC-03EudraT number: 2006-005017-36
• Study Type: interventional
• Target: 40
• Locations: 5 countries
• Sites: 5

Brief Summary

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.

Conditions

Metastatic Breast Cancer; Advanced Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Clinical efficacy measured by objective response rate (best response during the course of the study)

Secondary Outcomes (9)

• Efficacy:

• Clinical benefit rate

• Duration of response

• Time to progression (TTP)

• Safety:

Interventions

ertumaxomab BIOLOGICAL

10 µg, IV on day 0 followed by 100 µg every 7 days up to a maximum of 12 infusions.

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Neovii Biotech: lead

Study Sites (5)

Unknown Facility

Study Site, Austria

Location

Unknown Facility

Study Site, France

Location

Unknown Facility

Study Sites, Germany

Location

Unknown Facility

Study Site, Italy

Location

Unknown Facility

Barcelona, Spain

Location

Related Publications (4)

• 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.

  PMID: 16707606 BACKGROUND

• 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.

  PMID: 10901380 BACKGROUND

• 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.

  PMID: 10415020 BACKGROUND

• 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.

  PMID: 11588051 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ertumaxomab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• José Baselga / Javier Cortes

  Hospital Vall d'Hebron, Barcelona, Spain

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 26, 2007
• First Posted: March 27, 2007
• Study Start: March 1, 2007
• Study Completion: February 1, 2009
• Last Updated: May 19, 2009

Record last verified: 2009-05

Locations

AU (1); DE (1); IT (1); FR (1); ES (1)