Afatinib alone or in combination with vinorelbine in patients with HER2 positive breast cancer suffering from brain metastases

Conditions: HER2 positive breast cancer with progressive brain metastases after trastuzumab or lapatinib based therapy
MedDRA version: 14.0Level: PTClassification code 10006198Term: Breast cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2010-021415-16-FI

Lead Sponsor: Boehringer Ingelheim

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 120

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

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%.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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, <br>;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 Outcome Measures

Name	Time	Method
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.<br>Overall survival is the time from randomisation to death from any cause.