Clinical trial NCT01441596: 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
Official title: Lux-Breast 3; Randomised Phase II Study of Afatinib Alone or in Combination With Vinorelbine Versus Investigator's Choice of Treatment in Patients With HER2 Positive Breast Cancer With Progressive Brain Metastases After Trastuzumab and/or Lapatinib Based Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Neoplasms
Neoplasm Metastasis
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2011-09-27
Enrollment: 121
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Patient Benefit Rate at 12 Weeks
timeFrame: 12 weeks from randomisation
Secondary outcomes:
measure: Progression-Free Survival
timeFrame: From first drug administration until 28 days after end of treatment, up to 805 days
measure: Overall Survival
timeFrame: From first drug administration until 28 days after end of treatment, up to 805 days
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: 1200.67.10106 Boehringer Ingelheim Investigational Site
state: California
city: Fullerton
country: United States
facility: 1200.67.10105 Boehringer Ingelheim Investigational Site
state: California
city: Los Angeles
country: United States
facility: 1200.67.10001 Boehringer Ingelheim Investigational Site
state: California
city: Santa Barbara
country: United States
facility: 1200.67.10108 Boehringer Ingelheim Investigational Site
state: California
city: Lake Success
country: United States
facility: 1200.67.10003 Boehringer Ingelheim Investigational Site
state: New York
city: Columbus
country: United States
facility: 1200.67.10004 Boehringer Ingelheim Investigational Site
state: Ohio
city: Toronto
country: Canada
facility: 1200.67.11004 Boehringer Ingelheim Investigational Site
state: Ontario
city: Greenfield Park
country: Canada
facility: 1200.67.11003 Boehringer Ingelheim Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: 1200.67.11002 Boehringer Ingelheim Investigational Site
state: Quebec
city: Helsinki
country: Finland
facility: 1200.67.35801 Boehringer Ingelheim Investigational Site
city: Tampere
country: Finland
facility: 1200.67.35802 Boehringer Ingelheim Investigational Site
city: Turku
country: Finland
facility: 1200.67.35803 Boehringer Ingelheim Investigational Site
city: Caen Cedex
country: France
facility: 1200.67.33009 Boehringer Ingelheim Investigational Site
city: Clermont-Ferrand cedex 1
country: France
facility: 1200.67.33010 Boehringer Ingelheim Investigational Site
city: Lille Cedex
country: France
facility: 1200.67.33008 Boehringer Ingelheim Investigational Site
city: Lyon Cedex 08
country: France
facility: 1200.67.33001 Boehringer Ingelheim Investigational Site
city: Marseille Cedex 09
country: France
facility: 1200.67.33004 Boehringer Ingelheim Investigational Site
city: Nice Cedex 02
country: France
facility: 1200.67.33011 Boehringer Ingelheim Investigational Site
city: Paris Cedex 05
country: France
facility: 1200.67.33002 Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 1200.67.33003 Boehringer Ingelheim Investigational Site
city: Saint Cloud
country: France
facility: 1200.67.33012 Boehringer Ingelheim Investigational Site
city: Saint Herblain Cedex
country: France
facility: 1200.67.33005 Boehringer Ingelheim Investigational Site
city: Erlangen
country: Germany
facility: 1200.67.49002 Boehringer Ingelheim Investigational Site
city: Essen
country: Germany
facility: 1200.67.49008 Boehringer Ingelheim Investigational Site
city: Hannover
country: Germany
facility: 1200.67.49005 Boehringer Ingelheim Investigational Site
city: Heidelberg
country: Germany
facility: 1200.67.49006 Boehringer Ingelheim Investigational Site
city: MÃ¼nchen
country: Germany
facility: 1200.67.49007 Boehringer Ingelheim Investigational Site
city: Oldenburg
country: Germany
facility: 1200.67.49003 Boehringer Ingelheim Investigational Site
city: TÃ¼bingen
country: Germany
facility: 1200.67.49004 Boehringer Ingelheim Investigational Site
city: Modena
country: Italy
facility: 1200.67.39001 Boehringer Ingelheim Investigational Site
city: Reggio Emilia
country: Italy
facility: 1200.67.39002 Boehringer Ingelheim Investigational Site
city: Goyang
country: Korea, Republic of
facility: 1200.67.82001 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1200.67.82002 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1200.67.82003 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1200.67.82004 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1200.67.34002 Boehringer Ingelheim Investigational Site
city: CÃ³rdoba
country: Spain
facility: 1200.67.34006 Boehringer Ingelheim Investigational Site
city: L'Hospitalet de Llobregat
country: Spain
facility: 1200.67.34005 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1200.67.34003 Boehringer Ingelheim Investigational Site
city: Valencia
country: Spain
facility: 1200.67.34004 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Cortes J, Dieras V, Ro J, Barriere J, Bachelot T, Hurvitz S, Le Rhun E, Espie M, Kim SB, Schneeweiss A, Sohn JH, Nabholtz JM, Kellokumpu-Lehtinen PL, Taguchi J, Piacentini F, Ciruelos E, Bono P, Ould-Kaci M, Roux F, Joensuu H. Afatinib alone or afatinib plus vinorelbine versus investigator's choice of treatment for HER2-positive breast cancer with progressive brain metastases after trastuzumab, lapatinib, or both (LUX-Breast 3): a randomised, open-label, multicentre, phase 2 trial. Lancet Oncol. 2015 Dec;16(16):1700-10. doi: 10.1016/S1470-2045(15)00373-3. Epub 2015 Nov 17.