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

Breast Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01441596
• Other study ID #: 1200.67
• Secondary ID: 2010-021415-16
• Status: Completed
• Phase: Phase 2
• First received: September 26, 2011
• Last updated: August 25, 2015
• Start date: October 2011
• Est. completion date: August 2014

Study information

• Verified date: August 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaFinland: Finnish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesItaly: Ethics CommitteeSouth Korea: Ministry of Food and Drug Safety (MFDS)Spain: Ministry of HealthUnited States: Food and Drug Administration
• Study type: Interventional

Clinical 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: August 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Neoplasm Metastasis
• Neoplasms

Intervention

Drug:
• Vinorelbine
Vinorelbine 25 mg/m² on days 1, 8, 15 in a 3-weekly course
• 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.
• afatinib
Afatinib monotherapy:once daily, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg.
• afatinib
Afatinib monotherapy:once daily, continuous treatment in a 3-weekly course. If well tolerated, the dose may be escalated to 50 mg.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Canada,  Finland,  France,  Germany,  Italy,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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.	From first drug administration until 28 days after end of treatment, up to 805 days	No
Secondary	Overall Survival	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	No

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