LUX-Breast 1: BIBW 2992 (Afatinib) in HER2-positive Metastatic Breast Cancer Patients After One Prior Herceptin Treatment

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01125566
First received: May 10, 2010
Last updated: August 5, 2014
Last verified: August 2014

May 10, 2010
August 5, 2014
June 2010
June 2013   (final data collection date for primary outcome measure)
Progression-free Survival (PFS) [ Time Frame: From randomization until disease progression, death or data cut-off (08Jun2013); Up to 34 months ] [ Designated as safety issue: No ]

PFS is defined as time from randomisation to disease progression or death whichever occurs first. Assessed by investigator according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1).

Only data collected until the cut-off date for RECIST 1.1 based endpoints (08Jun2013) were considered.

Progression of disease was determined if at least 1 of the following criteria applied:

  • At least a 20% increase in the sum of the diameters (SoD) of target lesions taking as reference the smallest SoD recorded since the treatment started, together with an absolute increase in the SoD of at least 5 mm
  • Appearance of 1 or more new lesions
  • Unequivocal progression of existing non-target lesions
The primary endpoint of this study is progression-free survival, defined as the time from the date of randomisation to the date of disease progression, or to the date of death if a patient died earlier [ Time Frame: 25 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01125566 on ClinicalTrials.gov Archive Site
  • Objective Response (OR) [ Time Frame: Post baseline tumour-imaging was performed at Week 8, 16, 24, 32, 40, 48, 56 and then every 12 weeks (Up to 34 months) ] [ Designated as safety issue: No ]

    OR is defined as complete response (CR) and partial response (PR). Assessed by investigator according to RECIST 1.1.

    Only data collected until the cut-off date 08Jun2013 were considered. Complete Response (CR) for target lesions (TL): Disappearance of all target lesions.

    Complete Response (CR) for non-target lesions (NTL): Disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (<10mm short axis)

    Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.

    Other factors which add to the overall response of an imaging timepoint as PR are as below:-

    • CR in TL, but non-CR/Non-PD in NTL leads to PR
    • CR in TL, but not evaluated NTL leads to PR
    • PR in TL, but non-PD NTL or not all evaluated NTL leads to PR
  • Best RECIST Assessment [ Time Frame: Post baseline tumour-imaging was performed at Week 8, 16, 24, 32, 40, 48, 56 and then every 12 weeks (Data collected until cut-off date 08Jun2013; Up to 34 months) ] [ Designated as safety issue: No ]

    Best RECIST assessment is defined as CR, PR, stable disease (SD), PD or not evaluable by investigator (RECIST version 1.1).

    CR for target lesions (TL): Disappearance of all target lesions.

    CR for non-target lesions (NTL): Disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (<10mm short axis).

    PR: At least a 30% decrease in the sum of diameters (SoD) of target lesions taking as reference the baseline sum diameters.

    SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as references the smallest SoD while on study.

    PD: At least a 20% increase in the SoD of target lesions, taking as references the smallest sum on study (this includes the baseline sum if that is the smallest on study). Also, the sum must also demonstrate an absolute increase of a least 5mm. Appearance of one or more new lesions.

  • Overall Survival (OS) [ Time Frame: From randomisation to data cut-off (03Sep2013); Up to 37 months. ] [ Designated as safety issue: No ]

    OS is defined as time from randomisation to death irrespective of the cause of the death.

    For patients who had not died up to the cut-off date (03Sep2013), the date they were last known to be alive was derived from the patient status records, the trial completion record, radiological imaging assessments, the study treatment termination record, and the randomisation date.

  • Best RECIST assessment [ Time Frame: 25 months ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 42 months ] [ Designated as safety issue: No ]
  • Tumour shrinkage [ Time Frame: 25 months ] [ Designated as safety issue: No ]
  • Time to deterioration [ Time Frame: 25 months ] [ Designated as safety issue: No ]
  • Health-Related Quality of Life [ Time Frame: 25 months ] [ Designated as safety issue: No ]
  • analysis of safety: Adverse events as well as laboratory parameters will be graded according to CTCAE, Version 3.0 [ Time Frame: 25 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics: trough BIBW 2992 plasma concentrations at steady state, inter-individual and intra-individual variability, correlation with safety and efficacy data. [ Time Frame: 25 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
LUX-Breast 1: BIBW 2992 (Afatinib) in HER2-positive Metastatic Breast Cancer Patients After One Prior Herceptin Treatment
LUX-Breast 1; An Open Label, Randomised Phase III Trial of BIBW 2992 and Vinorelbine Versus Trastuzumab and Vinorelbine in Patients With Metastatic HER2-overexpressing Breast Cancer Failing One Prior Trastuzumab Treatment

To investigate the efficacy and safety of BIBW 2992 in combination with vinorelbine i.v. chemotherapy as treatment in patients with HER2-overexpressing, metastatic breast cancer, who failed one prior trastuzumab (Herceptin®) treatment

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Neoplasms
  • Drug: BIBW 2992
    patients receive BIBW 2992 tablets once daily and can reduce dose for adverse event management
  • Drug: trastuzumab
    patients receive trastuzumab 2mg/kg intravenously every week
  • Drug: vinorelbine
    patients receive vinorelbine 25mg/m² intravenously every week
  • Active Comparator: Arm B: trastuzumab with vinorelbine
    patients receive weekly intravenous infusion of trastuzumab and vinorelbine
    Interventions:
    • Drug: trastuzumab
    • Drug: vinorelbine
  • Experimental: Arm A: BIBW 2992 with vinorelbine
    patients receive BIBW 2992 tablets once daily combined with weekly intravenous infusion of vinorelbine
    Interventions:
    • Drug: BIBW 2992
    • Drug: vinorelbine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
508
May 2018
June 2013   (final data collection date for primary outcome measure)

Inclusion criteria:

  • Histologically confirmed diagnosis of HER2-overexpression breast cancer
  • Stage IV metastatic disease
  • Must have progressed on one prior trastuzumab treatment
  • no more than one prior trastuzumab based therapy regimen (either adjuvant or first-line)
  • Must have received anthracycline and/or taxane based chemotherapy for adjuvant treatment of breast cancer or first-line treatment of metastatic breast cancer
  • Must have (archived) tumour tissue sample available for central re-assessment of HER2-status
  • At least one measurable lesion according to RECIST 1.1.
  • ECOG score of 0 or 1 .

Exclusion criteria:

  • Prior treatment with EGFR/HER2-targeted small molecules or antibodies other than trastuzumab
  • Prior treatment with vinorelbine
  • Known pre-existing interstitial lung disease
  • Active brain metastases
  • History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to randomisation.
  • Cardiac left ventricular function with resting ejection fraction of less than 50%.
  • Patients unable to comply with the protocol.
  • Any contraindications for therapy with vinorelbine or trastuzumab.
  • Known hypersensitivity to BIBW 2992 or the excipients of any of the trial drugs.
  • Use of any investigational drug within 4 weeks of randomisation.
  • Inadequate hepatic, renal and haematologic organ function
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Russian Federation,   United States,   Canada,   Egypt,   South Africa,   Netherlands,   Belgium,   France,   Spain,   Portugal,   Ireland,   Lithuania,   Latvia,   Belarus,   Slovenia,   Italy,   Czech Republic,   Slovakia,   Austria,   United Kingdom,   Poland,   Germany,   Peru,   Mexico,   Argentina,   Brazil,   Chile,   Australia,   Singapore,   Japan,   Korea, Republic of,   China,   Taiwan,   Turkey,   India,   Sri Lanka,   Lebanon,   Israel
 
NCT01125566
1200.75, 2009-015476-98
Not Provided
Boehringer Ingelheim
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Boehringer Ingelheim
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP