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

NCT01441596 | Completed Phase 2 Results

• 2 other identifiers: 1200.672010-021415-16
• Study Type: interventional
• Target: 121
• Locations: 8 countries
• Sites: 40

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

Conditions

Breast Neoplasms; Neoplasm Metastasis

Outcome Measures

Primary Outcomes (1)

• Patient Benefit Rate at 12 Weeks

  Percentage of patients with patient benefit at week 12. Patient benefit was defined by the absence of central nervous system (CNS) disease progression according to Response Evaluation Criteria in Solid Tumours (RECIST) version 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 according to RECIST 1.1

  12 weeks from randomisation

Secondary Outcomes (2)

• Progression-Free Survival

  From first drug administration until 28 days after end of treatment, up to 805 days

• Overall Survival

  From first drug administration until 28 days after end of treatment, up to 805 days

Study Arms (3)

arm A: Afatinib monotherapy

EXPERIMENTAL

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.

Drug: afatinib

arm B: Afatinib in combination with vino

EXPERIMENTAL

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.

Drug: Vinorelbine; Drug: afatinib

arm C: investigator's choice of treatmen

ACTIVE COMPARATOR

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.

Drug: Investigator's choice of treatment

Interventions

Vinorelbine DRUG

Vinorelbine 25 mg/m² on days 1, 8, 15 in a 3-weekly course

arm B: Afatinib in combination with vino

Investigator's choice of treatment DRUG

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.

arm C: investigator's choice of treatmen

afatinib DRUG

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

arm B: Afatinib in combination with vino

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.
• 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).
• 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.
• 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.
• 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.

You may not qualify if:

• Prior treatment with HER2- tyrosine kinase inhibitor other than lapatinib
• 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).
• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (40)

1200.67.10106 Boehringer Ingelheim Investigational Site

Bakersfield, California, United States

Location

1200.67.10105 Boehringer Ingelheim Investigational Site

Fullerton, California, United States

Location

1200.67.10001 Boehringer Ingelheim Investigational Site

Los Angeles, California, United States

Location

1200.67.10108 Boehringer Ingelheim Investigational Site

Santa Barbara, California, United States

Location

1200.67.10003 Boehringer Ingelheim Investigational Site

Lake Success, New York, United States

Location

1200.67.10004 Boehringer Ingelheim Investigational Site

Columbus, Ohio, United States

Location

1200.67.11004 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Location

1200.67.11003 Boehringer Ingelheim Investigational Site

Greenfield Park, Quebec, Canada

Location

1200.67.11002 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

Location

1200.67.35801 Boehringer Ingelheim Investigational Site

Helsinki, Finland

Location

1200.67.35802 Boehringer Ingelheim Investigational Site

Tampere, Finland

Location

1200.67.35803 Boehringer Ingelheim Investigational Site

Turku, Finland

Location

1200.67.33009 Boehringer Ingelheim Investigational Site

Caen, France

Location

1200.67.33010 Boehringer Ingelheim Investigational Site

Clermont-Ferrand, France

Location

1200.67.33008 Boehringer Ingelheim Investigational Site

Lille, France

Location

1200.67.33001 Boehringer Ingelheim Investigational Site

Lyon, France

Location

1200.67.33004 Boehringer Ingelheim Investigational Site

Marseille, France

Location

1200.67.33011 Boehringer Ingelheim Investigational Site

Nice, France

Location

1200.67.33002 Boehringer Ingelheim Investigational Site

Paris, France

Location

1200.67.33003 Boehringer Ingelheim Investigational Site

Paris, France

Location

1200.67.33012 Boehringer Ingelheim Investigational Site

Saint-Cloud, France

Location

1200.67.33005 Boehringer Ingelheim Investigational Site

Saint-Herblain, France

Location

1200.67.49002 Boehringer Ingelheim Investigational Site

Erlangen, Germany

Location

1200.67.49008 Boehringer Ingelheim Investigational Site

Essen, Germany

Location

1200.67.49005 Boehringer Ingelheim Investigational Site

Hanover, Germany

Location

1200.67.49006 Boehringer Ingelheim Investigational Site

Heidelberg, Germany

Location

1200.67.49007 Boehringer Ingelheim Investigational Site

München, Germany

Location

1200.67.49003 Boehringer Ingelheim Investigational Site

Oldenburg, Germany

Location

1200.67.49004 Boehringer Ingelheim Investigational Site

Tübingen, Germany

Location

1200.67.39001 Boehringer Ingelheim Investigational Site

Modena, Italy

Location

1200.67.39002 Boehringer Ingelheim Investigational Site

Reggio Emilia, Italy

Location

1200.67.82001 Boehringer Ingelheim Investigational Site

Goyang, South Korea

Location

1200.67.82002 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1200.67.82003 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1200.67.82004 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1200.67.34002 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1200.67.34006 Boehringer Ingelheim Investigational Site

Córdoba, Spain

Location

1200.67.34005 Boehringer Ingelheim Investigational Site

L'Hospitalet de Llobregat, Spain

Location

1200.67.34003 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1200.67.34004 Boehringer Ingelheim Investigational Site

Valencia, Spain

Location

Related Publications (1)

• 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.

  PMID: 26596672 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Vinorelbine; Afatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Amides; Organic Chemicals; Quinazolines

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2011
• First Posted: September 27, 2011
• Study Start: October 1, 2011
• Primary Completion: February 1, 2014
• Study Completion: August 1, 2014
• Last Updated: September 7, 2015
• Results First Posted: February 25, 2015

Record last verified: 2015-08

Locations

CA (3); DE (7); KR (4); IT (2); ES (5); FI (3); US (6); FR (10)