Breast NeoplasmsPhase 2NCT01441596
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
A Phase 2 study testing Vinorelbine, Investigator's choice of treatment and afatinib in people with Breast Neoplasms and Neoplasm Metastasis, run by Boehringer Ingelheim at 40 sites in 8 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Neoplasms, Neoplasm Metastasis
- What is being tested?
- Vinorelbine, Investigator's choice of treatment and afatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 121 participants
- Where
- 40 sitesin 8 countries
- Study dates
- Oct 2011to Aug 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
40 sites in 8 countries.
40 sites in 8 countries
France10 sites
1200.67.33009 Boehringer Ingelheim Investigational Site
Caen
1200.67.33010 Boehringer Ingelheim Investigational Site
Clermont-Ferrand
1200.67.33008 Boehringer Ingelheim Investigational Site
Lille
1200.67.33001 Boehringer Ingelheim Investigational Site
Lyon
1200.67.33004 Boehringer Ingelheim Investigational Site
Marseille
1200.67.33011 Boehringer Ingelheim Investigational Site
Nice
1200.67.33002 Boehringer Ingelheim Investigational Site
Paris
1200.67.33003 Boehringer Ingelheim Investigational Site
Paris
1200.67.33012 Boehringer Ingelheim Investigational Site
Saint-Cloud
1200.67.33005 Boehringer Ingelheim Investigational Site
Saint-Herblain
Germany7 sites
1200.67.49002 Boehringer Ingelheim Investigational Site
Erlangen
1200.67.49008 Boehringer Ingelheim Investigational Site
Essen
1200.67.49005 Boehringer Ingelheim Investigational Site
Hanover
1200.67.49006 Boehringer Ingelheim Investigational Site
Heidelberg
1200.67.49007 Boehringer Ingelheim Investigational Site
München
1200.67.49003 Boehringer Ingelheim Investigational Site
Oldenburg
1200.67.49004 Boehringer Ingelheim Investigational Site
Tübingen
United States6 sites
1200.67.10106 Boehringer Ingelheim Investigational Site
Bakersfield, California
1200.67.10004 Boehringer Ingelheim Investigational Site
Columbus, Ohio
1200.67.10105 Boehringer Ingelheim Investigational Site
Fullerton, California
1200.67.10003 Boehringer Ingelheim Investigational Site
Lake Success, New York
1200.67.10001 Boehringer Ingelheim Investigational Site
Los Angeles, California
1200.67.10108 Boehringer Ingelheim Investigational Site
Santa Barbara, California
Spain5 sites
1200.67.34002 Boehringer Ingelheim Investigational Site
Barcelona
1200.67.34006 Boehringer Ingelheim Investigational Site
Córdoba
1200.67.34005 Boehringer Ingelheim Investigational Site
L'Hospitalet de Llobregat
1200.67.34003 Boehringer Ingelheim Investigational Site
Madrid
1200.67.34004 Boehringer Ingelheim Investigational Site
Valencia
South Korea4 sites
1200.67.82001 Boehringer Ingelheim Investigational Site
Goyang
1200.67.82002 Boehringer Ingelheim Investigational Site
Seoul
1200.67.82003 Boehringer Ingelheim Investigational Site
Seoul
1200.67.82004 Boehringer Ingelheim Investigational Site
Seoul
Canada3 sites
1200.67.11003 Boehringer Ingelheim Investigational Site
Greenfield Park, Quebec
1200.67.11002 Boehringer Ingelheim Investigational Site
Montreal, Quebec
1200.67.11004 Boehringer Ingelheim Investigational Site
Toronto, Ontario
Finland3 sites
1200.67.35801 Boehringer Ingelheim Investigational Site
Helsinki
1200.67.35802 Boehringer Ingelheim Investigational Site
Tampere
1200.67.35803 Boehringer Ingelheim Investigational Site
Turku
Italy2 sites
1200.67.39001 Boehringer Ingelheim Investigational Site
Modena
1200.67.39002 Boehringer Ingelheim Investigational Site
Reggio Emilia
About this study
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
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
- Being tested
- Vinorelbine, Investigator's choice of treatment, afatinib
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VinorelbineDrug
Vinorelbine 25 mg/m² on days 1, 8, 15 in a 3-weekly course
Investigator's choice of treatmentDrug
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.
afatinibDrug
Afatinib monotherapy:once daily, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg.
afatinibDrug
Afatinib monotherapy:once daily, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Investigator's choice of treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 weeks from randomisation
Secondary outcomes (2)
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.
Measured: From first drug administration until 28 days after end of treatment, up to 805 days
Overall Survival
Overall Survival is defined as time from randomisation to the date of death from any cause.
Measured: From first drug administration until 28 days after end of treatment, up to 805 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2011 (estimated)
- Study startOct 2011
- Primary completionFeb 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01441596
- Sponsor's protocol ID
- 1200.67
- Other IDs
- 2010-021415-16
- Status last verified
- Aug 2015
- First submitted
- 26 Sep 2011
- Last updated
- 7 Sep 2015
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 26596672
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01441596
- Acronym / sponsor ID
- 1200.67
- Conditions
- Breast Neoplasms, Neoplasm Metastasis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 121 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Oct 2011
- Primary completion
- Feb 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 27 Sep 2011 (estimated)
- Results
- Posted 25 Feb 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| arm A: Afatinib monotherapy | Experimental | Drug: afatinibAfatinib 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 B: Afatinib in combination with vino | Experimental | Drug: Vinorelbine, Drug: afatinibAfatinib 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 C: investigator's choice of treatmen | Active comparator | Drug: Investigator's choice of treatmentPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VinorelbineVinorelbine 25 mg/m² on days 1, 8, 15 in a 3-weekly course | Drug | arm B: Afatinib in combination with vino |
| Investigator's choice of treatmentPatients 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 | arm C: investigator's choice of treatmen |
| afatinibAfatinib monotherapy:once daily, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg. | Drug | arm B: Afatinib in combination with vino |
| afatinibAfatinib monotherapy:once daily, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg. | Drug | arm A: Afatinib monotherapy |
Primary outcome
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
2 secondary outcomes
Progression-Free Survival
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26596672Cortes 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.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
40 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vinorelbine, Investigator's choice of treatment and afatinib in people with Breast Neoplasms and Neoplasm Metastasis, run by Boehringer Ingelheim at 40 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in France, Germany, United States, Spain, South Korea and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Feb 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patient Benefit Rate at 12 Weeks (time frame: 12 weeks from randomisation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01441596, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2015.