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

NCT00522457 | Terminated Phase 2 Results DMC

• 1 other identifier: IV-ERT-BC-04
• Study Type: interventional
• Target: 19
• Locations: 2 countries
• Sites: 5

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.

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

Outcome Measures

Primary Outcomes (1)

• Clinical Efficacy Measured by Objective Response Rate (Best Response During the Course of the Study)

  patients are monitored for 6 months

Secondary Outcomes (2)

• Duration of Response

  patients are monitored for 6 months

• Clinical Benefit Rate

  patients are monitored for 6 months

Interventions

ertumaxomab DRUG

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

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Neovii Biotech: lead
• Fresenius Biotech North America: collaborator

Study Sites (5)

Unknown Facility

Minneapolis, Minnesota, United States

Location

Unknown Facility

Lebanon, New Hampshire, United States

Location

Unknown Facility

New York, New York, United States

Location

Unknown Facility

Ottawa, Ontario, Canada

Location

Unknown Facility

Montreal, Quebec, Canada

Location

Related Publications (5)

• 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

• 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

• 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.

  PMID: 11410615 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

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ertumaxomab

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

The study was prematurely terminated. This decision was based on strategic changes in the company's research and development program and resulted in limited patient data.

Results Point of Contact

• Title: Manager of Regulatory Affairs
• Organization: Fresenius Biotech North America

bao.le@fresenius-biotech.com

781-699-4652

Study Officials

• Gary Schwartz, MD

  Dartmouth Hitchcock Medical Center/Norris Cotton Cancer Center; Lebanon, NH

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: August 28, 2007
• First Posted: August 29, 2007
• Study Start: January 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: April 29, 2011
• Results First Posted: April 29, 2011

Record last verified: 2011-04

Locations

US (3); CA (2)