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

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 IV breast cancer, Her-2/neu expressing breast cancer, Her-2/neu, Trastuzumab refractory

Eligibility Criteria

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

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

Sites / Locations

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Duration of Response
The study was prematurely terminated, therefore no participants were analyzed
Clinical Benefit Rate
The study was prematurely terminated, therefore no participants were analyzed

Full Information

First Posted
August 28, 2007
Last Updated
April 28, 2011
Sponsor
Neovii Biotech
Collaborators
Fresenius Biotech North America
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1. Study Identification

Unique Protocol Identification Number
NCT00522457
Brief Title
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

2. Study Status

Record Verification Date
April 2011
Overall Recruitment Status
Terminated
Why Stopped
change in development plan, not due to safety concerns.
Study Start Date
January 2008 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
December 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Neovii Biotech
Collaborators
Fresenius Biotech North America

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

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 IV breast cancer, Her-2/neu expressing breast cancer, Her-2/neu, Trastuzumab refractory

7. Study Design

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

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
ertumaxomab
Intervention Description
Ertumaxomab will be intravenously administered to see if it can increase the patient's objective response rate.
Primary Outcome Measure Information:
Title
Clinical Efficacy Measured by Objective Response Rate (Best Response During the Course of the Study)
Time Frame
patients are monitored for 6 months
Secondary Outcome Measure Information:
Title
Duration of Response
Description
The study was prematurely terminated, therefore no participants were analyzed
Time Frame
patients are monitored for 6 months
Title
Clinical Benefit Rate
Description
The study was prematurely terminated, therefore no participants were analyzed
Time Frame
patients are monitored for 6 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gary Schwartz, MD
Organizational Affiliation
Dartmouth Hitchcock Medical Center/Norris Cotton Cancer Center; Lebanon, NH
Official's Role
Principal Investigator
Facility Information:
City
Minneapolis
State/Province
Minnesota
Country
United States
City
Lebanon
State/Province
New Hampshire
Country
United States
City
New York
State/Province
New York
Country
United States
City
Ottawa
State/Province
Ontario
Country
Canada
City
Montreal
State/Province
Quebec
Country
Canada

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
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
background
PubMed Identifier
11410615
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.
Results Reference
background
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
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Phase II Study With the Trifunctional Antibody Ertumaxomab to Treat Metastatic Breast Cancer After Progression on Trastuzumab Therapy

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