X-Breast 1; An open label, randomised phase III trial of BIBW 2992 and vinorelbine versus trastuzumab and vinorelbine in patients with metastatic HER2-overexpressing breast cancer failing one prior trastuzumab treatment - LUX-Breast 1

Conditions: Patients with metastatic HER2 over-expressing breast cancer
MedDRA version: 9.1Level: LLTClassification code 10057654
MedDRA version: 9.1Level: LLTClassification code 10065430
MedDRA version: 9.1Level: LLTClassification code 10027475

Registration Number: EUCTR2009-015476-98-IT

Lead Sponsor: BOEHRINGER ING.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 950

Inclusion Criteria

1. Female patients >=18 years 2. Histologically confirmed diagnosis of HER2-overexpression breast cancer 3. Stage IV metastatic disease 4. Must have progressed on one prior trastuzumab treatment, i.e. patients with a. First-line metastatic breast cancer failing on adjuvant trastuzumab or failing within 12 months of completion of adjuvant trastuzumab treatment; prior trastuzumab treatment must have been at least 9 weeks; b. Second-line metastatic breast cancer failing on first-line trastuzumab or failing within 6 months of completion of first-line trastuzumab treatment; prior trastuzumab treatment must have been at least 6 weeks. 5. Must not have received and failed more than one prior trastuzumab based therapy regimen (either adjuvant or first-line) 6. Must have received anthracycline and/or taxane based chemotherapy for adjuvant treatment of breast cancer or first-line treatment of metastatic breast cancer 7. Must have (archived) tumour tissue sample available for central re-assessment of HER2-status and prove HER2-positive. HER2 status must be confirmed by sponsor contracted laboratory prior to randomisation. HER2 over-expression is defined as IHC 3+ or IHC 2+ with reflex FISH positive confirmation 8. At least one measurable lesion according to RECIST 1.1. Patient with only skin lesion will not be eligible. 9. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1. 10. Life expectancy of at least six (6) months. 11. Written informed consent that is consistent with ICH-GCP guidelines 12. Must be eligible for treatment with trastuzumab and vinorelbine
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. Prior treatment with EGFR/HER2-targeted small molecules or antibodies other than trastuzumab 2. Prior treatment with vinorelbine 3. Known pre-existing interstitial lung disease 4. Radiotherapy, chemotherapy, hormone therapy, immunotherapy or surgery (other than biopsy) within 4 weeks (2 weeks for hormone therapy) prior to randomisation. 5. Active brain metastases (defined as stable for <4 weeks and/or symptomatic and/or requiring changes of treatment with anticonvulsants or steroids within the past 4 weeks and/or leptomeningeal disease). Patients with known history of brain metastases should undergo a baseline brain image to ensure that the disease is stable 6. Any other current malignancy or malignancy diagnosed within the past five (5) years (other than non-melanomatous skin cancer and in situ cervical cancer). 7. Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom e.g. Crohn`s disease, malabsorption or CTC grade =2 diarrhoea of any aetiology. 8. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to randomisation. 9. Cardiac left ventricular function with resting ejection fraction of less than 50%. 10. Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug. 11. Absolute neutrophil count (ANC) < 1500 / mm**3. 12. Platelet count < 75,000 / mm**3 13. Calculated creatinine clearance < 60 ml / min (using Cockcroft-Gault formula for GFR estimate, see appendix 1) or serum creatinine > 1.5 times upper limit of normal. 14. Bilirubin > 1.5 times upper limit of normal. 15. Aspartate amino transferase (AST) or alanine amino transferase (ALT) > 2.5 times the upper limit of normal (ULN) (if related to liver metastases > 5 times ULN). 16. Women of childbearing potential, unwilling to use a medically acceptable method of contraception during the trial, see Section 5.2.2.4. 17. Pregnancy or breast-feeding. 18. Patients unable to comply with the protocol. 19. Known hepatitis B infection, known hepatitis C infection or known HIV carrier. 20. Known or suspected active drug or alcohol abuse. 21. Requirement for treatment with any of the prohibited concomitant medications listed in section 4.2.2.1. 22. Any contraindications for therapy with vinorelbine or trastuzumab. 23. Known hypersensitivity to BIBW 2992 or the excipients of any of the trial drugs. 24. Use of any investigational drug within 4 weeks of randomisation.