E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006201 |
E.1.2 | Term | Breast cancer stage III |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006202 |
E.1.2 | Term | Breast cancer stage IV |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 during or after endocrine therapy. HER-2/neu 2+ patients must have a negative FISH test. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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 prior or concurrent chemotherapy in advanced or metastatic setting 10. Any concurrent hormonal therapy, immunotherapy or corticoid therapy 11. Any concurrent investigational treatment for advanced or metastatic disease 12. History of relevant cardiovascular disease as follows: Left ventricular ejection fraction (LVEF) below the institution’s lower limit of normal, based on echocardiography (ECHO)/Multiple Gated Acquisition scan (MUGA) 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 |
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |