Safety and Efficacy Study of the Trifunctional Antibody Ertumaxomab to Treat Patients With Advanced or Metastatic Breast Cancer

Breast Cancer Clinical Trial

— IV REXBC 02  

Official title:

Phase II Study of the Trifunctional Anti-HER-2/Neu x Anti-CD3 Antibody Ertumaxomab for Hormone Therapy Refractory Patients With Her-2/Neu 1+ or 2+ Expressing Advanced or Metastatic Breast Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00351858
• Other study ID #: FBT-IVREXBC 02
• Secondary ID: EudraT number: 2
• Status: Terminated
• Phase: Phase 2
• First received: July 12, 2006
• Last updated: April 30, 2015
• Start date: July 2006
• Est. completion date: February 2009

Study information

• Verified date: April 2015
• Source: Neovii Biotech
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentSpain: Spanish Agency of MedicinesRussia: Pharmacological Committee, Ministry of HealthItaly: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety and efficacy of the investigational trifunctional anti-Her-2/neu x anti-CD3 antibody ertumaxomab as treatment for hormone therapy refractory Her-2/neu 1+ or 2+ expressing advanced or metastatic breast cancer

Description:

A multi-centre, phase II study of ertumaxomab in metastatic breast cancer patients who became progressive after hormonal therapy. Each eligible patient will receive three ascending doses of ertumaxomab, administered intravenously. Ertumaxomab will be administered as a 3-hour constant rate infusion with a dosing interval of 7 days. Each patient will participate in this study for up to 7 months (includes the up to 21 days screening period, 14 days treatment period, and up to 180 days/6 months follow-up), with 3-monthly post-study follow-up until the patient becomes progressive.

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:

• Female gender, and if of child-bearing potential must have negative pregnancy test result within 2 days before enrolment and must agree to practice effective birth control during the study.

• Aged 18 years and older.

• Histologically or cytologically confirmed invasive breast cancer with stage IIIb or IV disease with documented progression.

• Measurable disease according to RECIST.

• Histologically documented advanced primary breast cancer or biopsy of metastatic site demonstrating HER-2/neu expression (HER-2/neu 1+ or 2+, determined by immunohistochemistry [IHC]). HER-2/neu 2+ patients must have a negative Fluorescence In Situ Hybridization [FISH] test result.

• Hormone receptor status Estrogen Receptors (ERs) positive and/or Progesterone Receptors (PRs) positive.

• No prior treatment with mouse or rat antibodies.

• Life expectancy of at least six months (if the life expectancy of a patient is unspecified she will be allowed to enter the study).

• An Eastern Cooperative Oncology Group (ECOG) performance score of £ 1.

• Patients must have had disease progression after hormonal therapy including at least one aromatase inhibitor.

• Adequate hematological, liver and kidney function:

• Thrombocytes ³ 100000 / mm³ (= 100 x 109 /l)

• Hemoglobin ³ 10 g/dl

• Neutrophil count ³ 1500/mm³ (= 1.5 x 109 /l)

• WBC ³ 3 X 109 /l

• Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT) = 2.5 x upper limit of normal (ULN)

• Serum bilirubin = 2 x ULN

• Creatinine = 1.5 x ULN or clearance ³ 60 ml/min

• No life-threatening visceral disease.

• No known brain or central nervous system metastases.

• No symptomatic pleural effusions.

• No symptomatic pericardial effusions.

• No subjects whose only site of metastatic involvement is bone metastases with the exception of those with a measurable soft tissue component of the bone lesion seen with imaging that does not require palliative radiation intervention and/or the patient has a lytic bone lesion ³ 1 cm measured with radiography that can be followed for evidence of re-calcification.

• No history of relevant cardiovascular disease:

• LVEF within the institutional ranges of normal as measured by echocardiogram or MUGA scan

• No prior uncontrolled or symptomatic congestive heart failure NYHA ³ 2

• No myocardial infarction within the past two years

• No uncontrolled or symptomatic cardiac arrhythmias

• No severe dyspnea.

• No pulmonary dysfunction or need for continuous supportive oxygen inhalation.

• No other concurrent uncontrolled co-morbid illness.

• No other concurrent malignancy, except treated basal cell or squamous cell carcinoma of the skin, or in situ carcinoma of the cervix.

• Patients with documented autoimmune diseases (such as lupus) are excluded from participation in the study unless a waiver is granted by the responsible medical monitor.

• Patients with a human immunodeficiency virus, hepatitis B or hepatitis C positive status are excluded from participation in the study.

• No prior or concurrent chemotherapy regimen for advanced or metastatic disease.

• Prior neo-adjuvant or adjuvant chemotherapy is allowed provided it was stopped at least six months before study entry.

• No concurrent hormone therapy (hormone therapy must be stopped at the screening visit).

• At least 4 weeks since prior radiotherapy.

• No concurrent immune therapy.

• No concurrent corticosteroid therapy.

• No regularly used medication for a health condition or comorbidity that might result in undue risk to the patient.

• No prior investigational treatment for advanced or metastatic disease.

• Able and willing to comply fully with the protocol.

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

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• ertumaxomab

Locations

Country	Name	City	State
Belgium	Jules Bordet Institute, Free University of Brussels	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Neovii Biotech

Country where clinical trial is conducted

Belgium, 

References & Publications (6)

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

Lindhofer H, Mocikat R, Steipe B, Thierfelder S. Preferential species-restricted heavy/light chain pairing in rat/mouse quadromas. Implications for a single-step purification of bispecific antibodies. J Immunol. 1995 Jul 1;155(1):219-25. — 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, Mayer A, Gires O, Schmitt B, Mack B, Lindhofer H, Wollenberg B, Walz A. TNFalpha contributes to the antitumor activity of a bispecific, trifunctional antibody. Anticancer Res. 2001 Sep-Oct;21(5):3499-503. — 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	To demonstrate clinical efficacy of the investigational trifunctional antibody ertumaxomab for the treatment of hormone therapy refractory advanced or metastatic breast cancer tumors (stage IIIb or IV) which are known to express Her-2/neu (1+ or 2+)
Secondary	Time to progression
Secondary	Duration of response
Secondary	Time to response
Secondary	Clinical benefit of ertumaxomab (defined as the rate of confirmed complete remission, partial remission and stable disease)
Secondary	Tumor marker levels (CA 15-3 and CEA)