Afatinib in HER2 (Human Epidermal Growth Factor Receptor)-treatment failures

LUX-Breast 2;An open label, phase II trial of BIBW 2992 (afatinib) in patients with metastatic HER2-overexpressing breast cancer failing HER2-targeted treatment in the neoadjuvant and/or adjuvant treatment setting - LUX-Breast 2; BIBW 2992 in metastatic HER2 over-expressing breast cancer

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2010-021945-29-GB

Enrollment

Registered

2010-10-22

Start date

2011-02-18

Completion date

Unknown

Last updated

2019-04-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HER2 - overexpressing breast cancer MedDRA version: 19.0 Level: PT Classification code 10057654 Term: Breast cancer female System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 19.0 Level: PT Classification code 10006202 Term: Breast cancer stage IV System Organ Class: 100291

Interventions

Trade Name: GIOTRIF 40 mg film-coated tablets Product Name: afatinib Product Code: BIBW 2992 Pharmaceutical Form: Film-coated tablet INN

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1.Female patients =18 years 2. Proven diagnosis of HER2-overexpressing, histologically confirmed breast cancer, Patients must have an archived tissue sample available for central re-assessment of HER2-status. 3.Stage IV metastatic disease. 4. At least one measurable lesion according to RECIST 1.1. Skin, bone and brain lesions are considered non-target lesions. 5. Life expectancy of at least six (6) months. 6. Must have failed or progressed trastuzumab or lapatanib or trastuzumab and lapatanib treatment in the neoadjuvant and/or adjuvant setting and on BIBW 2992 (afatinib) monotherapy in the 1st line metastatic setting (for patients in the second part of the trial). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 53 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 27

Exclusion criteria

Exclusion criteria: 1. Requirement for treatment with any of the prohibited concomitant medications 2. Quickly progressing visceral disease 3. Known pre-existing interstitial lung disease 4. Prior first line therapy for metastatic breast cancer 5. Radiotherapy, chemotherapy, immunotherapy, trastuzumab or lapatinib treatment or surgery (other than biopsy) within 4 weeks prior to trial treatment. Treatment with palliative radiotherapy (short course to non-target lesions) is allowed. 6. Hormone therapy for breast cancer within 2 weeks prior to trial treatment 7. Active brain metastases (defined as stable for 1.5 times upper limit of normal 15. Bilirubin > 1.5 times upper limit of normal. 16. Aspartate amino transferase (AST) or alanine amino transferase (ALT) > three times the upper limit of normal (ULN) (if related to liver metastases > five times ULN). 17. Prior treatment with paclitaxel in the past 12 months. 18. Platelet count < 100 x 109/L

Design outcomes

Primary

Measure	Time frame
Main Objective: To investigate the efficacy and safety of BIBW 2992 (afatinib) alone and in combination with weekly treatment with paclitaxel or vinorelbine (in patients who progress on BIBW 2992 (afatinib) monotherapy only) as a new treatment algorithm in patients with HER2-overexpressing, metastatic breast cancer, who failed HER2-targeted treatment in the neoadjuvant and/or adjuvant setting. The primary endpoint is Objective Response (OR) assessed by RECIST 1.1 ; Secondary Objective: The secondary and other endpoints for this study are: 1. Best overall response during each treatment period according to RECIST 1.1 2. Duration of objective response 3. Progression-Free Survival (PFS) 4. Safety assessed by the severity and incidence of adverse event according to Common Terminology Criteria for Adverse Events (Version 3.0), changes in vital signs and safety laboratory parameters 5. Incidence of new brain metastases 6. ECOG performance status 7. Overall survival 8. Percentage change from baseline in tumour size ;Primary end point(s): Objective Response (OR) assessed by RECIST 1.1;Timepoint(s) of evaluation of this end point: In each trial part (monotherapy and combination-therapy) objective response will be calculated based on the best response to therapy (according to RECIST 1.1). Response to therapy will be evaluated every six weeks from start of monotherapy and then every six weeks from start of combination therapy until end of treatment.	—

Measure

Time frame

Main Objective: To investigate the efficacy and safety of BIBW 2992 (afatinib) alone and in combination with weekly treatment with paclitaxel or vinorelbine (in patients who progress on BIBW 2992 (afatinib) monotherapy only) as a new treatment algorithm in patients with HER2-overexpressing, metastatic breast cancer, who failed HER2-targeted treatment in the neoadjuvant and/or adjuvant setting. The primary endpoint is Objective Response (OR) assessed by RECIST 1.1 ; Secondary Objective: The secondary and other endpoints for this study are: 1. Best overall response during each treatment period according to RECIST 1.1 2. Duration of objective response 3. Progression-Free Survival (PFS) 4. Safety assessed by the severity and incidence of adverse event according to Common Terminology Criteria for Adverse Events (Version 3.0), changes in vital signs and safety laboratory parameters 5. Incidence of new brain metastases 6. ECOG performance status 7. Overall survival 8. Percentage change from baseline in tumour size ;Primary end point(s): Objective Response (OR) assessed by RECIST 1.1;Timepoint(s) of evaluation of this end point: In each trial part (monotherapy and combination-therapy) objective response will be calculated based on the best response to therapy (according to RECIST 1.1). Response to therapy will be evaluated every six weeks from start of monotherapy and then every six weeks from start of combination therapy until end of treatment.

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Secondary

Measure	Time frame
Secondary end point(s): • Best overall response during each treatment period according to RECIST 1.1 • Duration of objective response, defined as the time from first objective response to the time of progression or death. • Progression-Free Survival (PFS) will be defined for three time intervals: time from the date of the start of monotherapy to the date of 1st disease progression; time from the date of the start of combination therapy to the date of 2nd disease progression and the time from the date of the start of monotherapy to the date of 2nd disease progression. In each case, the date of death will be used if a patient died before the appropriate progression. The analysis will be based upon the evaluation of tumour imaging performed by the investigator using RECIST Version 1.1. • Safety assessed by the severity and incidence of adverse event according to Common Terminology Criteria for Adverse Events (CTC s, AE Version 3.0), changes in vital signs and safety laboratory parameters ; Timepoint(s) of evaluation of this end point: Response to therapy and duration of objective response will be evaluated every 6 weeks from start of monotherapy and then every 6 weeks from start of combination therapy until end of treatment. Progression free survival will be calculated based on response to therapy (according to RECIST 1.1) and vital status. Occurrence of adverse events will be recorded at every study visit up to the first follow-up visit (and at subsequent follow-up visits if ongoing at first follow-up visit or treatment related). Vital signs will be evaluated at every visit. Specimens for evaluation of laboratory tests will be obtained at the screening visit, at the start of each 3-weekly treatment course, at the end of treatment visit and at each follow-up visit.	—

Measure

Time frame

Secondary end point(s): • Best overall response during each treatment period according to RECIST 1.1 • Duration of objective response, defined as the time from first objective response to the time of progression or death. • Progression-Free Survival (PFS) will be defined for three time intervals: time from the date of the start of monotherapy to the date of 1st disease progression; time from the date of the start of combination therapy to the date of 2nd disease progression and the time from the date of the start of monotherapy to the date of 2nd disease progression. In each case, the date of death will be used if a patient died before the appropriate progression. The analysis will be based upon the evaluation of tumour imaging performed by the investigator using RECIST Version 1.1. • Safety assessed by the severity and incidence of adverse event according to Common Terminology Criteria for Adverse Events (CTC s, AE Version 3.0), changes in vital signs and safety laboratory parameters ; Timepoint(s) of evaluation of this end point: Response to therapy and duration of objective response will be evaluated every 6 weeks from start of monotherapy and then every 6 weeks from start of combination therapy until end of treatment. Progression free survival will be calculated based on response to therapy (according to RECIST 1.1) and vital status. Occurrence of adverse events will be recorded at every study visit up to the first follow-up visit (and at subsequent follow-up visits if ongoing at first follow-up visit or treatment related). Vital signs will be evaluated at every visit. Specimens for evaluation of laboratory tests will be obtained at the screening visit, at the start of each 3-weekly treatment course, at the end of treatment visit and at each follow-up visit.

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Countries

Poland, Romania, United Kingdom

Contacts

Public ContactQRPE PSC CT Information Disclosure

Boehringer Ingelheim Pharma GmbH & Co. KG

clintriage.rdg@boehringer-ingelheim.com0018002430127

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026