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

NCT ID: NCT01441596

Last Updated: 2015-09-07

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

121 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-10-31

Study Completion Date

2014-08-31

Brief Summary

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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

Detailed Description

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Conditions

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Breast Neoplasms Neoplasm Metastasis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

afatinib

Intervention Type 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

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.

Group Type EXPERIMENTAL

Vinorelbine

Intervention Type DRUG

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

afatinib

Intervention Type DRUG

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

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.

Group Type ACTIVE_COMPARATOR

Investigator's choice of treatment

Intervention Type 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.

Interventions

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Vinorelbine

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

Intervention Type 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.

Intervention Type DRUG

afatinib

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

afatinib

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

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Boehringer Ingelheim

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

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1200.67.10106 Boehringer Ingelheim Investigational Site

Bakersfield, California, United States

Site Status

1200.67.10105 Boehringer Ingelheim Investigational Site

Fullerton, California, United States

Site Status

1200.67.10001 Boehringer Ingelheim Investigational Site

Los Angeles, California, United States

Site Status

1200.67.10108 Boehringer Ingelheim Investigational Site

Santa Barbara, California, United States

Site Status

1200.67.10003 Boehringer Ingelheim Investigational Site

Lake Success, New York, United States

Site Status

1200.67.10004 Boehringer Ingelheim Investigational Site

Columbus, Ohio, United States

Site Status

1200.67.11004 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Site Status

1200.67.11003 Boehringer Ingelheim Investigational Site

Greenfield Park, Quebec, Canada

Site Status

1200.67.11002 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

Site Status

1200.67.35801 Boehringer Ingelheim Investigational Site

Helsinki, , Finland

Site Status

1200.67.35802 Boehringer Ingelheim Investigational Site

Tampere, , Finland

Site Status

1200.67.35803 Boehringer Ingelheim Investigational Site

Turku, , Finland

Site Status

1200.67.33009 Boehringer Ingelheim Investigational Site

Caen, , France

Site Status

1200.67.33010 Boehringer Ingelheim Investigational Site

Clermont-Ferrand, , France

Site Status

1200.67.33008 Boehringer Ingelheim Investigational Site

Lille, , France

Site Status

1200.67.33001 Boehringer Ingelheim Investigational Site

Lyon, , France

Site Status

1200.67.33004 Boehringer Ingelheim Investigational Site

Marseille, , France

Site Status

1200.67.33011 Boehringer Ingelheim Investigational Site

Nice, , France

Site Status

1200.67.33002 Boehringer Ingelheim Investigational Site

Paris, , France

Site Status

1200.67.33003 Boehringer Ingelheim Investigational Site

Paris, , France

Site Status

1200.67.33012 Boehringer Ingelheim Investigational Site

Saint-Cloud, , France

Site Status

1200.67.33005 Boehringer Ingelheim Investigational Site

Saint-Herblain, , France

Site Status

1200.67.49002 Boehringer Ingelheim Investigational Site

Erlangen, , Germany

Site Status

1200.67.49008 Boehringer Ingelheim Investigational Site

Essen, , Germany

Site Status

1200.67.49005 Boehringer Ingelheim Investigational Site

Hanover, , Germany

Site Status

1200.67.49006 Boehringer Ingelheim Investigational Site

Heidelberg, , Germany

Site Status

1200.67.49007 Boehringer Ingelheim Investigational Site

München, , Germany

Site Status

1200.67.49003 Boehringer Ingelheim Investigational Site

Oldenburg, , Germany

Site Status

1200.67.49004 Boehringer Ingelheim Investigational Site

Tübingen, , Germany

Site Status

1200.67.39001 Boehringer Ingelheim Investigational Site

Modena, , Italy

Site Status

1200.67.39002 Boehringer Ingelheim Investigational Site

Reggio Emilia, , Italy

Site Status

1200.67.82001 Boehringer Ingelheim Investigational Site

Goyang, , South Korea

Site Status

1200.67.82002 Boehringer Ingelheim Investigational Site

Seoul, , South Korea

Site Status

1200.67.82003 Boehringer Ingelheim Investigational Site

Seoul, , South Korea

Site Status

1200.67.82004 Boehringer Ingelheim Investigational Site

Seoul, , South Korea

Site Status

1200.67.34002 Boehringer Ingelheim Investigational Site

Barcelona, , Spain

Site Status

1200.67.34006 Boehringer Ingelheim Investigational Site

Córdoba, , Spain

Site Status

1200.67.34005 Boehringer Ingelheim Investigational Site

L'Hospitalet de Llobregat, , Spain

Site Status

1200.67.34003 Boehringer Ingelheim Investigational Site

Madrid, , Spain

Site Status

1200.67.34004 Boehringer Ingelheim Investigational Site

Valencia, , Spain

Site Status

Countries

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United States Canada Finland France Germany Italy South Korea Spain

References

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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.

Reference Type DERIVED
PMID: 26596672 (View on PubMed)

Other Identifiers

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2010-021415-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1200.67

Identifier Type: -

Identifier Source: org_study_id

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