Lux-Breast 3; Afatinib Alone or in Combination With Vinorelbine in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) Positive Breast Cancer Suffering From Brain Metastases
Condition: Breast Neoplasms; Neoplasm Metastasis
MeSH terms: Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Breast Neoplasms
Intervention: Vinorelbine; Investigator's choice of treatment; afatinib; afatinib
Intervention description: Vinorelbine 25 mg/mÂ² on days 1, 8, 15 in a 3-weekly course; Patients will receive, at the investigator's discretion, the most appropriate medical treatment consisting of single agent or combination regimen approved for the treatment of metastatic breast cancer, and according to patient status and local guidelines.; Afatinib monotherapy:once daily, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg.; Afatinib monotherapy:once daily, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg.
Intervention MeSH terms: Vinorelbine; Afatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 121.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The aim of this study is to investigate the efficacy and safety of afatinib alone or in
      combination with vinorelbine, as treatment in patients with HER2-overexpressing metastatic
      breast cancer, who have progressive brain lesions after trastuzumab and/or lapatinib based
      therapy
    

Eligibility criteria:

        Inclusion criteria:

          1. patients with HER2 positive breast cancer with a documented central nervous system
             (CNS) recurrence/progression (by imaging) during or after a HER2 inhibitor
             (Trastuzumab and/or Lapatinib) based therapy (no leptomeningeal carcinomatosis as the
             only site of CNS metastases)

          2. at least one measurable and progressive lesion in the brain (=10 mm on T1-weighted,
             gadolinium-enhanced Magnetic Resonance Imaging). Measurable or non measurable
             extracranial metastases allowed.

          3. previous treatment with HER2 inhibitors to be discontinued prior to first study
             treatment administration (at least 14 days for trastuzumab and other antibodies, at
             least 7 days for lapatinib).

          4. previous chemotherapy and hormonal therapy (adjuvant and metastatic regimens) allowed,
             but chemotherapy must have been discontinued at least 14 days and hormonal therapy at
             least 7 days prior to first study treatment administration.

          5. Patients must have recovered to baseline condition or to Common Terminology Criteria
             for Adverse Events (CTCAE) version 3.0 grade = 1 from any acute CTCAE v. 3.0 grade =2
             side effects of previous treatments.

          6. prior surgery, whole brain radiotherapy or stereotactic radiosurgery allowed provided
             that there is unequivocal evidence of one or more new and/or progressive brain
             metastases after completion of whole brain radiotherapy or stereotactic radiosurgery.

        Exclusion criteria:

          1. Prior treatment with HER2- tyrosine kinase inhibitor other than lapatinib

          2. Any other current malignancy or malignancy diagnosed within the past five (5) years
             (other than bilateral primary breast cancer, metastases to the contralateral breast,
             non-melanomatous skin cancer and in situ cervical cancer).

          3. Significant chronic or recent acute gastrointestinal disorders with diarrhoea as a
             major symptom e.g. Crohn's disease, malabsorption or Common Terminology Criteria (CTC)
             grade =2 diarrhoea of any aetiology.