Metastatic breast cancer patients with intermediate HER2 expression (IHC 2+, HER2 FISH-negative) MedDRA version: 14.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: BIBW 2992 (Afatinib)
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Afatinib
CAS Number: 850140-72-6
Current Sponsor code: BIBW 2992
Other descriptive name: AFATINIB
Concen
Sponsors
Medizinische Fakultät der Otto-von-Guericke Universität Magdeburg Universitätsklinikum Magdeburg A.ö.R.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female patients = 18 years 2. Histologically confirmed diagnosis of intermediate HER2-overexpressing breast cancer 3. Stage IV metastatic disease 4. Must have received anthracycline-based chemotherapy for adjuvant treatment of breast cancer or first-line treatment of metastatic breast cancer 5. Must have received one first-line chemotherapy for metastatic breast cancer 6. Must have (archived) tumour tissue sample available for central re-assessment of HER2 status and prove to be intermediate HER2-positive. HER2 intermediate status is defined as IHC 2+ and FISH-negativity. 7. Must have at least one measurable lesion according to RECIST 1.1 (R09-0262). Patient with only skin lesions will not be eligible. 8. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 (R01-0787). 9. Life expectancy of at least six (6) months. 10. Written informed consent that is consistent with ICH-GCP guidelines. 11. Must be eligible for treatment with BIBW 2992 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 32 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: 1. Prior treatment with EGFR/HER2-targeted tyrosine kinase inhibitors, i.e. lapatinib 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 start of treatment with BIBW 2992 and vinorelbine. 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 imaging by e.g. CT scan or MRI to ensure that the disease is stable. 6. 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. 7. 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 start of study treatment. 8. Cardiac left ventricular function with resting ejection fraction of less than 50 %. 9. Women of childbearing potential, unwilling to use a medically acceptable method of contraception during the trial, see Section 5.2.2.4. 10. Pregnancy or breast-feeding. 11. Known hepatitis B infection, known hepatitis C infection or known HIV carrier.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the efficacy and safety of BIBW 2992 in combination with vinorelbine i.v. chemotherapy as treatment in patients with HER2 IHC 2+, HER2 FISH-negative , metastatic breast cancer after failure of first-line therapy for metastatic disease and having received anthracyclines;Secondary Objective: Objective Response Rate (ORR) based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1), Safety (Adverse events according to Common Terminology Criteria for Adverse Events (CTC AE Version 3.0)), Time-to-Progression (TTP), and Overall Survival (OS) ;Timepoint(s) of evaluation of this end point: Evaluation of primary objective will be done as soon as all relevant and corresponding data could be collected from all patients included ;Primary end point(s): The primary endpoint of this study is progression-free survival (PFS), defined as the time from the date of start of treatment to the date of disease progression, or to the date of death if a patient died earlier. The primary objective is to determine the 6-month PFS rate of BIBW 2992 and vinorelbine i.v. in patients with metastatic, HER2 IHC 2+, HER2 FISH-neg. breast cancer | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Objective Response Rate (ORR) based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1), Safety (Adverse events according to Common Terminology Criteria for Adverse Events (CTC AE Version 3.0)), Time-to-Progression (TTP), and Overall Survival (OS) ;Timepoint(s) of evaluation of this end point: Evaluation will be done after the last patient has completed the trial. | — |
Countries
Germany
Contacts
Public ContactKlinische Studienzentrale (CSC)
Medizinische Fakultät der Otto-von-Guericke Universität Magdeburg Universitätsklinikum Magdeburg A.ö.R.
Outcome results
None listed