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

This study has been terminated.
(change in development plan, not due to safety concerns.)
Sponsor:
Collaborator:
Fresenius Biotech North America
Information provided by:
Neovii Biotech
ClinicalTrials.gov Identifier:
NCT00522457
First received: August 28, 2007
Last updated: April 28, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Metastatic Breast Cancer
Advanced Breast Cancer
Drug: ertumaxomab
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Neovii Biotech:

Primary Outcome Measures:
  • Clinical Efficacy Measured by Objective Response Rate (Best Response During the Course of the Study) [ Time Frame: patients are monitored for 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of Response [ Time Frame: patients are monitored for 6 months ] [ Designated as safety issue: No ]
    The study was prematurely terminated, therefore no participants were analyzed

  • Clinical Benefit Rate [ Time Frame: patients are monitored for 6 months ] [ Designated as safety issue: No ]
    The study was prematurely terminated, therefore no participants were analyzed


Enrollment: 19
Study Start Date: January 2008
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: ertumaxomab
    Ertumaxomab will be intravenously administered to see if it can increase the patient's objective response rate.
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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00522457

Locations
United States, Minnesota
Minneapolis, Minnesota, United States
United States, New Hampshire
Lebanon, New Hampshire, United States
United States, New York
New York, New York, United States
Canada, Ontario
Ottawa, Ontario, Canada
Canada, Quebec
Montreal, Quebec, Canada
Sponsors and Collaborators
Neovii Biotech
Fresenius Biotech North America
Investigators
Principal Investigator: Gary Schwartz, MD Dartmouth Hitchcock Medical Center/Norris Cotton Cancer Center; Lebanon, NH
  More Information

Additional Information:
Publications:
Responsible Party: Manager of Regulatory Affairs, Fresenius Biotech North America
ClinicalTrials.gov Identifier: NCT00522457     History of Changes
Other Study ID Numbers: IV-ERT-BC-04
Study First Received: August 28, 2007
Results First Received: March 1, 2011
Last Updated: April 28, 2011
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Neovii Biotech:
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

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014