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

Primary Purpose

Metastatic Breast Cancer, Advanced Breast Cancer

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ertumaxomab
Sponsored by
Neovii Biotech
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Efficacy:
Clinical benefit rate
Duration of response
Time to progression (TTP)
Safety:
Incidence of adverse events (AEs)
Presence of human anti-murine antibodies after ertumaxomab infusion
Vital signs
Laboratory parameters

Full Information

First Posted
March 26, 2007
Last Updated
May 18, 2009
Sponsor
Neovii Biotech
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1. Study Identification

Unique Protocol Identification Number
NCT00452140
Brief Title
Phase II Study With the Trifunctional Antibody Ertumaxomab to Treat Metastatic Breast Cancer Progressing After Endocrine Treatment
Official Title
Phase II Study for Repeated Dosing of the Trifunctional Bispecific Anti-HER-2/Neu x Anti-CD3 Antibody Ertumaxomab in Patients With HER-2/Neu 1+ or 2+/FISH Negative Expressing Advanced or Metastatic Breast Cancer (Stage IIIb/IV) Progressing After Endocrine Treatment
Study Type
Interventional

2. Study Status

Record Verification Date
May 2009
Overall Recruitment Status
Terminated
Why Stopped
company focus on other projects
Study Start Date
March 2007 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
February 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Neovii Biotech

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
An open-label, non-randomized, uncontrolled, one-stage, phase II study evaluating the efficacy and safety of the investigational trifunctional bispecific antibody ertumaxomab (anti-Her-2/neu x anti-CD3) for the treatment of hormone therapy refractory advanced or metastatic breast cancer tumours (stage IIIb or IV) which are known to express HER-2/neu (1+ or 2+/FISH negative).Ertumaxomab will be administered at 7 day intervals by constant rate 3 hour intravenous (i.v.) infusions according to the following sequential dose schedule: 10 µg (day 0) and thereafter 100 µg flat doses once every 7 days (± 1 day) for a maximum of up to 12 weeks or until disease progression or any other unacceptable toxicity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
ertumaxomab
Intervention Description
10 µg, IV on day 0 followed by 100 µg every 7 days up to a maximum of 12 infusions.
Primary Outcome Measure Information:
Title
Clinical efficacy measured by objective response rate (best response during the course of the study)
Secondary Outcome Measure Information:
Title
Efficacy:
Title
Clinical benefit rate
Title
Duration of response
Title
Time to progression (TTP)
Title
Safety:
Title
Incidence of adverse events (AEs)
Title
Presence of human anti-murine antibodies after ertumaxomab infusion
Title
Vital signs
Title
Laboratory parameters

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
José Baselga / Javier Cortes
Organizational Affiliation
Hospital Vall d'Hebron, Barcelona, Spain
Official's Role
Principal Investigator
Facility Information:
City
Study site
Country
Austria
City
Study site
Country
France
City
Study sites
Country
Germany
City
Study site
Country
Italy
City
Barcelona
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
16707606
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.
Results Reference
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PubMed Identifier
10901380
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.
Results Reference
background
PubMed Identifier
10415020
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.
Results Reference
background
PubMed Identifier
11588051
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.
Results Reference
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Phase II Study With the Trifunctional Antibody Ertumaxomab to Treat Metastatic Breast Cancer Progressing After Endocrine Treatment

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