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

August 25, 2015 updated by: Boehringer Ingelheim

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

121

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada
        • 1200.67.11004 Boehringer Ingelheim Investigational Site
    • Quebec
      • Greenfield Park, Quebec, Canada
        • 1200.67.11003 Boehringer Ingelheim Investigational Site
      • Montreal, Quebec, Canada
        • 1200.67.11002 Boehringer Ingelheim Investigational Site
  • Finland
      • Helsinki, Finland
        • 1200.67.35801 Boehringer Ingelheim Investigational Site
      • Tampere, Finland
        • 1200.67.35802 Boehringer Ingelheim Investigational Site
      • Turku, Finland
        • 1200.67.35803 Boehringer Ingelheim Investigational Site
  • France
      • Caen Cedex, France
        • 1200.67.33009 Boehringer Ingelheim Investigational Site
      • Clermont-Ferrand cedex 1, France
        • 1200.67.33010 Boehringer Ingelheim Investigational Site
      • Lille Cedex, France
        • 1200.67.33008 Boehringer Ingelheim Investigational Site
      • Lyon Cedex 08, France
        • 1200.67.33001 Boehringer Ingelheim Investigational Site
      • Marseille Cedex 09, France
        • 1200.67.33004 Boehringer Ingelheim Investigational Site
      • Nice Cedex 02, France
        • 1200.67.33011 Boehringer Ingelheim Investigational Site
      • Paris, France
        • 1200.67.33003 Boehringer Ingelheim Investigational Site
      • Paris Cedex 05, France
        • 1200.67.33002 Boehringer Ingelheim Investigational Site
      • Saint Cloud, France
        • 1200.67.33012 Boehringer Ingelheim Investigational Site
      • Saint Herblain Cedex, France
        • 1200.67.33005 Boehringer Ingelheim Investigational Site
  • Germany
      • Erlangen, Germany
        • 1200.67.49002 Boehringer Ingelheim Investigational Site
      • Essen, Germany
        • 1200.67.49008 Boehringer Ingelheim Investigational Site
      • Hannover, Germany
        • 1200.67.49005 Boehringer Ingelheim Investigational Site
      • Heidelberg, Germany
        • 1200.67.49006 Boehringer Ingelheim Investigational Site
      • München, Germany
        • 1200.67.49007 Boehringer Ingelheim Investigational Site
      • Oldenburg, Germany
        • 1200.67.49003 Boehringer Ingelheim Investigational Site
      • Tübingen, Germany
        • 1200.67.49004 Boehringer Ingelheim Investigational Site
  • Italy
      • Modena, Italy
        • 1200.67.39001 Boehringer Ingelheim Investigational Site
      • Reggio Emilia, Italy
        • 1200.67.39002 Boehringer Ingelheim Investigational Site
  • Korea, Republic of
      • Goyang, Korea, Republic of
        • 1200.67.82001 Boehringer Ingelheim Investigational Site
      • Seoul, Korea, Republic of
        • 1200.67.82002 Boehringer Ingelheim Investigational Site
      • Seoul, Korea, Republic of
        • 1200.67.82003 Boehringer Ingelheim Investigational Site
      • Seoul, Korea, Republic of
        • 1200.67.82004 Boehringer Ingelheim Investigational Site
  • Spain
      • Barcelona, Spain
        • 1200.67.34002 Boehringer Ingelheim Investigational Site
      • Córdoba, Spain
        • 1200.67.34006 Boehringer Ingelheim Investigational Site
      • L'Hospitalet de Llobregat, Spain
        • 1200.67.34005 Boehringer Ingelheim Investigational Site
      • Madrid, Spain
        • 1200.67.34003 Boehringer Ingelheim Investigational Site
      • Valencia, Spain
        • 1200.67.34004 Boehringer Ingelheim Investigational Site
  • United States
    • California
      • Bakersfield, California, United States
        • 1200.67.10106 Boehringer Ingelheim Investigational Site
      • Fullerton, California, United States
        • 1200.67.10105 Boehringer Ingelheim Investigational Site
      • Los Angeles, California, United States
        • 1200.67.10001 Boehringer Ingelheim Investigational Site
      • Santa Barbara, California, United States
        • 1200.67.10108 Boehringer Ingelheim Investigational Site
    • New York
      • Lake Success, New York, United States
        • 1200.67.10003 Boehringer Ingelheim Investigational Site
    • Ohio
      • Columbus, Ohio, United States
        • 1200.67.10004 Boehringer Ingelheim Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: arm A: Afatinib monotherapy
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
Afatinib monotherapy:once daily, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg.
Experimental: arm B: Afatinib in combination with vino
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: afatinib
Afatinib monotherapy:once daily, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg.
Drug: Vinorelbine
Vinorelbine 25 mg/m² on days 1, 8, 15 in a 3-weekly course
Active Comparator: arm C: investigator's choice of treatmen
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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient Benefit Rate at 12 Weeks
Time Frame: 12 weeks from randomisation
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival
Time Frame: From first drug administration until 28 days after end of treatment, up to 805 days

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.
From first drug administration until 28 days after end of treatment, up to 805 days
Overall Survival
Time Frame: From first drug administration until 28 days after end of treatment, up to 805 days
Overall Survival is defined as time from randomisation to the date of death from any cause.
From first drug administration until 28 days after end of treatment, up to 805 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2011

Primary Completion (Actual)

February 1, 2014

Study Completion (Actual)

August 1, 2014

Study Registration Dates

First Submitted

September 26, 2011

First Submitted That Met QC Criteria

September 26, 2011

First Posted (Estimate)

September 27, 2011

Study Record Updates

Last Update Posted (Estimate)

September 7, 2015

Last Update Submitted That Met QC Criteria

August 25, 2015

Last Verified

August 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1200.67
  • 2010-021415-16 (EudraCT Number: EudraCT)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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