HER2 positive breast cancer with progressive brain metastases after trastuzumab or lapatinib based therapy MedDRA version: 14.0 Level: PT Classification code 10006198 Term: Breast cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Afatinib
Product Code: BIBW 2992
Pharmaceutical Form: Tablet
INN or Proposed INN: afatinib
Current Sponsor code: BIBW 2992
Concentration unit: mg milligram(s)
Concentration type: equal
C
Sponsors
Boehringer Ingelheim
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically confirmed diagnosis of HER2-overexpressing breast cancer (HER2 status as previously assessed by local lab is acceptable). • Documented CNS recurrence/progression during or after a HER2 inhibitor (i.e. Trastuzumab, Lapatinib) based therapy (no leptomeningeal carcinomatosis as the only site of CNS metastases) • At least one measurable and progressive lesion in the CNS (=10 mm on T1-weighted, gadolinium-enhanced MRI) after prior systemic and/or radiation therapy. Measurable or non-measurable extra cranial metastases allowed. 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
Exclusion criteria: Prior treatment with HER2-targeted treatment other than lapatinib and trastuzumab. • Any other current malignancy or malignancy diagnosed within the past five years (other than non-melanomatous skin cancer and in situ cervical cancer). • Significant chronic 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. • History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension (investigator’s assessment), congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia in the investigator’s opinion. • Cardiac left ventricular function by echocardiogram or MUGA scan with resting ejection fraction of less than 50%.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the antitumour activity and safety of afatinib alone or in combination with vinorelbine versus investigator’s choice of treatment for the treatment of patients with HER2-positive breast cancer with progressive brain metastases after trastuzumab or lapatinib based therapy;Secondary Objective: Analysis of progression free survival and overall survival, ;Primary end point(s): Patient benefit at 12 weeks defined as absence of CNS disease progression according to RECIST 1.1 in addition to: no tumour related worsening of the neurological signs and symptoms (NSS), no tumour related increase in corticosteroid dosage and no progression of extra CNS disease.;Timepoint(s) of evaluation of this end point: Tumor assessment every 6 weeks, including assessment by imaging and assessment of the neurological signs and symptoms and corticosteroid dosage | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Progression-free survival (PFS) and overall survival;Timepoint(s) of evaluation of this end point: Progression-free survival (PFS) is the time from randomisation until the occurrence of disease progression or death, whichever comes first. Overall survival is the time from randomisation to death from any cause. | — |
Countries
Canada, Finland, Germany, Italy, Korea, Republic of, Spain, United States
Contacts
Public ContactQRPE PSC CT Information Disclosure
Boehringer Ingelheim Pharma GmbH & Co. KG
Outcome results
None listed