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

Boehringer Ingelheim

Status and phase: Completed; Phase 2

Conditions: Neoplasm Metastasis; Breast Neoplasms

Treatments: Drug: Investigator's choice of treatment; Drug: Vinorelbine; Drug: afatinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01441596

2010-021415-16 (EudraCT Number)

1200.67

Details and patient eligibility

About

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

Enrollment: 121 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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121 participants in 3 patient groups

arm A: Afatinib monotherapy

Experimental group

Description:

Afatinib monotherapy: starting dose 40 mg per day, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg.

Treatment:

Drug: afatinib

Drug: afatinib

arm B: Afatinib in combination with vino

Experimental group

Description:

Afatinib 40 mg per day, continuous treatment, in combination with vinorelbine Vinorelbine 25 mg/m² on days 1, 8, 15 in a 3-weekly course.

Treatment:

Drug: Vinorelbine

Drug: afatinib

Drug: afatinib

arm C: investigator's choice of treatmen

Active Comparator group

Description:

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.

Treatment:

Drug: Investigator's choice of treatment