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 treatmentEstudio de fase II de la administración repetida del anticuerpoanti-HER-2/neu x anti-CD3 trifuncional biespecífico ertumaxomab enpacientes con cáncer de mama avanzado o metastásico (estadio IIIb/IV) conexpresión de HER-2/neu 1+ o 2+/negativo en FISH que progresan después detratamiento hormonal

• Conditions: MedDRA version: 9.1Level: LLTClassification code 10006202Term: Breast cancer stage IV; Hormone therapy refractory advanced or metastatic breast cancer tumors (stage IIIb or IV), which are known to express HER-2/neu (1+ or 2+) and are FISH negative.Cáncer de mama avanzado o metastásico (estadio IIIb o IV) que se sepa que expresa HER-2/neu (1+ o 2+)/negativo en FISH y que es resistente a hormonoterapia; MedDRA version: 9.1Level: LLTClassification code 10006201Term: Breast cancer stage III

• Registration Number: EUCTR2006-005017-36-ES
• Lead Sponsor: Fresenius Biotech GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-03-05
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 40

Inclusion Criteria

1. Signed and dated informed consent form
2. Female gender, aged >= 18 years and with a life expectancy of at least 6 months
3. Negative pregnancy test at screening (and not more than 72 hours prior to the first ertumaxomab infusion) for women of childbearing potential and patients must agree to use adequate contraception during the study
4. Histologic diagnosis of adenocarcinoma originating in the breast
5. Evidence that the cancer is locally advanced (stage IIIb) or metastatic (stage IV) and not curable by local measures i.e., surgery, radiation
6. Measurable disease, defined as at least one lesion that is measurable in one dimension (Response Evaluation Criteria in Solid Tumors [RECIST] criteria)
7. HER-2/neu expression 1+ or 2+ (confirmed by Dako HercepTest®). HER-2/neu 2+ patients must have a negative FISH test
8. Hormone receptor status Estrogen Receptors (ERs) positive and/or Progesterone Receptors (PRs) positive
9. Prior adequate endocrine therapy for advanced or metastatic disease.
10. Disease progression during or after endocrine therapy
11. No prior treatment with mouse or rat antibodies
12. Eastern Cooperative Oncology Group (ECOG) performance score of = 1
13. Adequate hematological, liver and kidney function: Thrombocytes >= 100000/mm³ (= 100 x 10E9/L). Neutrophil count >= 1500/mm³ (= 1.5 x 10E9/L). Serum glutamic oxaloacetic transaminase (SGOT/aspartate aminotransferase [AST]) and serum glutamic pyruvate transaminase [SGPT]/alanine aminotransferase [ALT]) within limits of normal; in patients with liver metastases <= 2.5 x upper limit of normal (ULN). Serum bilirubin within normal limits; in patients with liver metastases serum bilirubin <= 1.5 x ULN. Creatinine <= 1.5 x ULN or clearance = 60 mL/min. Partial thromboplastin time (PTT) within limits of normal
14. Adequate recovery from prior systemic therapy
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Women who are pregnant or breast-feeding
2. Known Human Immunodeficiency Virus (HIV) infection
3. Unable or unwilling to comply fully with the protocol
4. Any history or symptoms indicative of brain or central nervous system metastases
5. Patients with a 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)
6. Presence of autoimmune disease
7. Documented acute or chronic infection requiring antibiotic treatment
8. Concurrent non-malignant co-morbidities that are uncontrolled
9. Any concurrent chemotherapy, hormonal therapy, immunotherapy or corticoid therapy
10. Any concurrent investigational treatment for advanced or metastatic disease
11. 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. Uncontrolled angina pectoris. Myocardial infarction during the last 2 years

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective 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+ expressing advanced or metastatic breast cancer (stage III b/IV) which has progressed after endocrine therapy. HER-2/neu 2+ patients must have a negative FISH test.;Secondary Objective: The secondary objectives of the study are the evaluation of safety data and determination of further efficacy data in terms of time to progression (TTP), duration of response, and clinical benefit.;Primary end point(s): The primary endpoint is objective response rate (ORR) to ertumaxomab (best response during the course of the study), defined as the proportion of patients with complete response (CR) or partial response (PR) according to RECIST, relative to the total analysis set of evaluable patients. Only patients having received at least two ertumaxomab infusions will be evaluable.