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

Metastatic Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00452140
• Other study ID #: IV-ERT-BC-03
• Secondary ID: EudraT number: 2
• Status: Terminated
• Phase: Phase 2
• First received: March 26, 2007
• Last updated: May 18, 2009
• Start date: March 2007
• Est. completion date: February 2009

Study information

• Verified date: May 2009
• Source: Neovii Biotech
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food SafetySpain: Spanish Agency of MedicinesItaly: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Neovii Biotech

Countries where clinical trial is conducted

Austria,  France,  Germany,  Italy,  Spain, 

References & Publications (4)

Kiewe P, Hasmüller S, Kahlert S, Heinrigs M, Rack B, Marmé A, Korfel A, Jäger 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. — View 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. — View Citation

Zeidler R, Mysliwietz J, Csánady 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical efficacy measured by objective response rate (best response during the course of the study)
Secondary	Efficacy:
Secondary	Clinical benefit rate
Secondary	Duration of response
Secondary	Time to progression (TTP)
Secondary	Safety:
Secondary	Incidence of adverse events (AEs)
Secondary	Presence of human anti-murine antibodies after ertumaxomab infusion
Secondary	Vital signs
Secondary	Laboratory parameters