search
Back to results

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

Primary Purpose

Breast Neoplasms, Neoplasm Metastasis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Vinorelbine
Investigator's choice of treatment
afatinib
afatinib
Sponsored by
Boehringer Ingelheim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept 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.

Sites / Locations

  • 1200.67.10106 Boehringer Ingelheim Investigational Site
  • 1200.67.10105 Boehringer Ingelheim Investigational Site
  • 1200.67.10001 Boehringer Ingelheim Investigational Site
  • 1200.67.10108 Boehringer Ingelheim Investigational Site
  • 1200.67.10003 Boehringer Ingelheim Investigational Site
  • 1200.67.10004 Boehringer Ingelheim Investigational Site
  • 1200.67.11004 Boehringer Ingelheim Investigational Site
  • 1200.67.11003 Boehringer Ingelheim Investigational Site
  • 1200.67.11002 Boehringer Ingelheim Investigational Site
  • 1200.67.35801 Boehringer Ingelheim Investigational Site
  • 1200.67.35802 Boehringer Ingelheim Investigational Site
  • 1200.67.35803 Boehringer Ingelheim Investigational Site
  • 1200.67.33009 Boehringer Ingelheim Investigational Site
  • 1200.67.33010 Boehringer Ingelheim Investigational Site
  • 1200.67.33008 Boehringer Ingelheim Investigational Site
  • 1200.67.33001 Boehringer Ingelheim Investigational Site
  • 1200.67.33004 Boehringer Ingelheim Investigational Site
  • 1200.67.33011 Boehringer Ingelheim Investigational Site
  • 1200.67.33002 Boehringer Ingelheim Investigational Site
  • 1200.67.33003 Boehringer Ingelheim Investigational Site
  • 1200.67.33012 Boehringer Ingelheim Investigational Site
  • 1200.67.33005 Boehringer Ingelheim Investigational Site
  • 1200.67.49002 Boehringer Ingelheim Investigational Site
  • 1200.67.49008 Boehringer Ingelheim Investigational Site
  • 1200.67.49005 Boehringer Ingelheim Investigational Site
  • 1200.67.49006 Boehringer Ingelheim Investigational Site
  • 1200.67.49007 Boehringer Ingelheim Investigational Site
  • 1200.67.49003 Boehringer Ingelheim Investigational Site
  • 1200.67.49004 Boehringer Ingelheim Investigational Site
  • 1200.67.39001 Boehringer Ingelheim Investigational Site
  • 1200.67.39002 Boehringer Ingelheim Investigational Site
  • 1200.67.82001 Boehringer Ingelheim Investigational Site
  • 1200.67.82002 Boehringer Ingelheim Investigational Site
  • 1200.67.82003 Boehringer Ingelheim Investigational Site
  • 1200.67.82004 Boehringer Ingelheim Investigational Site
  • 1200.67.34002 Boehringer Ingelheim Investigational Site
  • 1200.67.34006 Boehringer Ingelheim Investigational Site
  • 1200.67.34005 Boehringer Ingelheim Investigational Site
  • 1200.67.34003 Boehringer Ingelheim Investigational Site
  • 1200.67.34004 Boehringer Ingelheim Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

arm A: Afatinib monotherapy

arm B: Afatinib in combination with vino

arm C: investigator's choice of treatmen

Arm 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.

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Progression-Free Survival
Progression-Free Survival is defined as the time from the date of randomisation to the date of disease progression or death whichever came first. Disease progression was defined as either disease progression in CNS lesions (including worsening in NSS and use of corticosteroid) or disease progression in extra-CNS lesions according to RECIST 1.1.
Overall Survival
Overall Survival is defined as time from randomisation to the date of death from any cause.

Full Information

First Posted
September 26, 2011
Last Updated
August 25, 2015
Sponsor
Boehringer Ingelheim
search

1. Study Identification

Unique Protocol Identification Number
NCT01441596
Brief Title
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

2. Study Status

Record Verification Date
August 2015
Overall Recruitment Status
Completed
Study Start Date
October 2011 (undefined)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
August 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim

4. Oversight

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Neoplasms, Neoplasm Metastasis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
121 (Actual)

8. Arms, Groups, and Interventions

Arm Title
arm A: Afatinib monotherapy
Arm Type
Experimental
Arm 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.
Arm Title
arm B: Afatinib in combination with vino
Arm Type
Experimental
Arm 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.
Arm Title
arm C: investigator's choice of treatmen
Arm Type
Active Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Vinorelbine
Intervention Description
Vinorelbine 25 mg/m² on days 1, 8, 15 in a 3-weekly course
Intervention Type
Drug
Intervention Name(s)
Investigator's choice of treatment
Intervention 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.
Intervention Type
Drug
Intervention Name(s)
afatinib
Intervention Description
Afatinib monotherapy:once daily, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg.
Intervention Type
Drug
Intervention Name(s)
afatinib
Intervention Description
Afatinib monotherapy:once daily, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg.
Primary Outcome Measure Information:
Title
Patient Benefit Rate at 12 Weeks
Description
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
Time Frame
12 weeks from randomisation
Secondary Outcome Measure Information:
Title
Progression-Free Survival
Description
Progression-Free Survival is defined as the time from the date of randomisation to the date of disease progression or death whichever came first. Disease progression was defined as either disease progression in CNS lesions (including worsening in NSS and use of corticosteroid) or disease progression in extra-CNS lesions according to RECIST 1.1.
Time Frame
From first drug administration until 28 days after end of treatment, up to 805 days
Title
Overall Survival
Description
Overall Survival is defined as time from randomisation to the date of death from any cause.
Time Frame
From first drug administration until 28 days after end of treatment, up to 805 days

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: 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. Exclusion criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Organizational Affiliation
Boehringer Ingelheim
Official's Role
Study Chair
Facility Information:
Facility Name
1200.67.10106 Boehringer Ingelheim Investigational Site
City
Bakersfield
State/Province
California
Country
United States
Facility Name
1200.67.10105 Boehringer Ingelheim Investigational Site
City
Fullerton
State/Province
California
Country
United States
Facility Name
1200.67.10001 Boehringer Ingelheim Investigational Site
City
Los Angeles
State/Province
California
Country
United States
Facility Name
1200.67.10108 Boehringer Ingelheim Investigational Site
City
Santa Barbara
State/Province
California
Country
United States
Facility Name
1200.67.10003 Boehringer Ingelheim Investigational Site
City
Lake Success
State/Province
New York
Country
United States
Facility Name
1200.67.10004 Boehringer Ingelheim Investigational Site
City
Columbus
State/Province
Ohio
Country
United States
Facility Name
1200.67.11004 Boehringer Ingelheim Investigational Site
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
1200.67.11003 Boehringer Ingelheim Investigational Site
City
Greenfield Park
State/Province
Quebec
Country
Canada
Facility Name
1200.67.11002 Boehringer Ingelheim Investigational Site
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
1200.67.35801 Boehringer Ingelheim Investigational Site
City
Helsinki
Country
Finland
Facility Name
1200.67.35802 Boehringer Ingelheim Investigational Site
City
Tampere
Country
Finland
Facility Name
1200.67.35803 Boehringer Ingelheim Investigational Site
City
Turku
Country
Finland
Facility Name
1200.67.33009 Boehringer Ingelheim Investigational Site
City
Caen Cedex
Country
France
Facility Name
1200.67.33010 Boehringer Ingelheim Investigational Site
City
Clermont-Ferrand cedex 1
Country
France
Facility Name
1200.67.33008 Boehringer Ingelheim Investigational Site
City
Lille Cedex
Country
France
Facility Name
1200.67.33001 Boehringer Ingelheim Investigational Site
City
Lyon Cedex 08
Country
France
Facility Name
1200.67.33004 Boehringer Ingelheim Investigational Site
City
Marseille Cedex 09
Country
France
Facility Name
1200.67.33011 Boehringer Ingelheim Investigational Site
City
Nice Cedex 02
Country
France
Facility Name
1200.67.33002 Boehringer Ingelheim Investigational Site
City
Paris Cedex 05
Country
France
Facility Name
1200.67.33003 Boehringer Ingelheim Investigational Site
City
Paris
Country
France
Facility Name
1200.67.33012 Boehringer Ingelheim Investigational Site
City
Saint Cloud
Country
France
Facility Name
1200.67.33005 Boehringer Ingelheim Investigational Site
City
Saint Herblain Cedex
Country
France
Facility Name
1200.67.49002 Boehringer Ingelheim Investigational Site
City
Erlangen
Country
Germany
Facility Name
1200.67.49008 Boehringer Ingelheim Investigational Site
City
Essen
Country
Germany
Facility Name
1200.67.49005 Boehringer Ingelheim Investigational Site
City
Hannover
Country
Germany
Facility Name
1200.67.49006 Boehringer Ingelheim Investigational Site
City
Heidelberg
Country
Germany
Facility Name
1200.67.49007 Boehringer Ingelheim Investigational Site
City
München
Country
Germany
Facility Name
1200.67.49003 Boehringer Ingelheim Investigational Site
City
Oldenburg
Country
Germany
Facility Name
1200.67.49004 Boehringer Ingelheim Investigational Site
City
Tübingen
Country
Germany
Facility Name
1200.67.39001 Boehringer Ingelheim Investigational Site
City
Modena
Country
Italy
Facility Name
1200.67.39002 Boehringer Ingelheim Investigational Site
City
Reggio Emilia
Country
Italy
Facility Name
1200.67.82001 Boehringer Ingelheim Investigational Site
City
Goyang
Country
Korea, Republic of
Facility Name
1200.67.82002 Boehringer Ingelheim Investigational Site
City
Seoul
Country
Korea, Republic of
Facility Name
1200.67.82003 Boehringer Ingelheim Investigational Site
City
Seoul
Country
Korea, Republic of
Facility Name
1200.67.82004 Boehringer Ingelheim Investigational Site
City
Seoul
Country
Korea, Republic of
Facility Name
1200.67.34002 Boehringer Ingelheim Investigational Site
City
Barcelona
Country
Spain
Facility Name
1200.67.34006 Boehringer Ingelheim Investigational Site
City
Córdoba
Country
Spain
Facility Name
1200.67.34005 Boehringer Ingelheim Investigational Site
City
L'Hospitalet de Llobregat
Country
Spain
Facility Name
1200.67.34003 Boehringer Ingelheim Investigational Site
City
Madrid
Country
Spain
Facility Name
1200.67.34004 Boehringer Ingelheim Investigational Site
City
Valencia
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
26596672
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.
Results Reference
derived
Links:
URL
http://trials.boehringer-ingelheim.com/
Description
Related Info

Learn more about this trial

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

We'll reach out to this number within 24 hrs