None listed
Conditions
Interventions
Group 1 Type of group
BIBW 2992 high dose once daily (allowed dose reduction to medium or low once daily in case of AE)
Group name:Group 3 Type of group
Trastuzumab 4mg/kg i.v. week 1, followed by 2mg/kg i.v. weekly.
Sponsors
Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI),
Eligibility
Sex/Gender
Female
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Female patients 18 years of age or older. • Histologically proven breast cancer patients who have not received any previous therapy. • Locally advanced Stage IIIA disease without evidence of distant metastatic disease in addition to the lymph nodes of the anatomical site. • HER2-positive patients (IHC HER2 3+, or HER2 2+ and FISH positive). • Patients with at least one lumoral lesion> 5 cm in diameter that can be accurately measured by clinical measurement and ultrasound in at least one dimension (the longest recorded diameter). • Patients must give their consent to undergo biopsies of fresh tumor tissue (fresh and paraffin-preserved material) taken to perform HER2 and biomarker analyzes for incorporation into the study, after 3 weeks of treatment and in the EOT. • Life expectancy of at least 6 months. • Informed written consent that is consistent with ICH-BPC guidelines and local legislation. • Eastem Cooperative Oncology Group (ECOG, ROl-0787) score of 0 or 1.
Exclusion criteria
Exclusion criteria: • Absolute neutrophil count (ANO) less than 1,500 / mm3. • Platelet count less than 100,000 / mm3. • Hemoglobin level less than 9.0 g / dl. • Bilirubin greater than 1.5 mg / dl (> 26 pmol / L, equivalent unit of SI). • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than double the upper limit of the standard • Serum creatinine greater than 1.5 times the normal upper limit or calculated / measured creatinine clearance 2 of any etiology in the initial evaluation. • Serious illness, concomitant non-cancer disease or mental problems that the researcher considers incompatible with the protocol. • Sexually active patients who are not willing to use a medically acceptable contraceptive method. • Pregnancy or breastfeeding. • Patients who cannot comply with the protocol. • Active alcohol or drug abuse. • Patients who have any other life-threatening organic disease or dysfunction that, in the opinion of the researcher, would compromise the patient´s safety or interfere with the safety assessment of the study drug. • Previous treatment for previous locally advanced breast cancer including treatment with other investigational drugs; other cancer therapies, e.g. chemotherapy, immunotherapy, radiotherapy or hormonal therapy (including LHRH agonists, or other endocrine / hormonal therapies for breast cancer), concomitantly with the treatment of this trial and / or during the last 4 weeks prior to the first treatment with the trial drug. Simultaneous treatment with bisphosphonates is allowed. • Previous treatment with Trastuzumab or EGFR or EGFR / HER2 inhibitors. • Other malignant tumors diagnosed in the last five (5) years (other than non-melanomato skin cancer and cervical cancer in situ). • Patients with any active infection would be 4 ^ s_ say, which requires an IV antibiotic, antifungals, or antiviral agents). • Patients with known HIV, active hepatitis B or active hepatitis C. • History of clinically significant or uncontrolled heart disease, including congestive heart failure, angina pectoris, acute myocardial infarction, arrhythmias, including functional classification of 3 according to the New York Heart Association (NYHA). • Cardiac function of the left ventricle with a resting ejection action of less than 50% measured according to the nuclear ventriculography of the heart (MUGA scan) or echocardiogram.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Objective response (complete or partial) was assessed according to RECIST 1.0 criteria. Measure:Objective Response (OR) Timepoints:Tumour assessments were performed at screening, day 22 and day 43 | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:CB was defined as CR, PR or stable disease (SD) and was assessed according to RECIST criteria regardless of treatment status. Measure:Number of Participants Who Achieved Clinical Benefit (CB) Timepoints:Tumour assessments were performed at screening, day 22 and day 43. ; Outcome name:Change was based on the primary lesion only rather that the sum of the target lesions as most patients had only one lesion. Measure:Change From Baseline in the Diameter of the Primary Target Lesion Timepoints:3 weeks or 6 weeks ; Outcome name:Individual drug plasma concentrations of afatinib after multiple oral administrations at day 7 Measure:Plasma Concentration of Afatinib Timepoints:Day 7 ; Outcome name:Changes in the biomarkers (Phospho-MAP-Kinase (MAPK), Total MAPK expression, EGFR, HER2, Phospho-EGFR and -HER2, Proliferation marker (Ki67 and p27), Apoptotic index (cleaved caspase 3), Phosphate and tensin homolog (PTEN), HER2 homodimerisation by HERmark assay and Phospho AKT) from biopsy tissue. Measure:Changes in Biomarker in Tumour Biopsies Timepoints:Screening, day 22, day 43 | — |
Countries
Argentina, Brazil, Chile, Colombia, Costa Rica, Mexico, Panama, Peru, United States
Outcome results
None listed