HER2-negative metastatic breast cancer after failure of no more than three chemotherapy regimen in two cohorts of patients
Conditions
Interventions
Product Name: BIBW 2992, 5 mg
Product Code: BIBW 2992
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: BIBW 2992
Concentration unit: mg milligram(s)
Concentration type: equal
Concentratio
Sponsors
Boehringer Ingelheim Pharma GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria for both cohorts of HER2-negative patients 1. Female Patients age 18 years or older. 2. Patients with histologically proven breast cancer, who failed or relapsed after no more than three lines of chemotherapy, including adjuvant. 3. HER2-negative patients (HER2 1+ or negative, or Her2 2+ and FISH negative if known). 4. Patients with at least one tumour lesion that can accurately be measured by magnetic resonance imaging (MRI), computed tomography (CT) or X-ray in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan. 5. Patients must have tumour samples available for EGFR-testing. 6. Life expectancy of at least six (6) months. 7. Written informed consent that is consistent with ICH-GCP guidelines and local law. 8. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score 0 or 1. 9. Evidence of metastatic breast cancer Additional inclusion criteria for Cohort A 10. HR-negative patients; ER-status and PgR-status must be assessed by IHC. Additional inclusion criteria for Cohort B 10 ER-and/or PgR-positive patients; ER-status and PgR-status must be assessed by IHC 11. Patients must sign informed consent form for pharmakogenetic analyses prior to analysis of EGFR/EGFR-ligand overexpression on mRNA basis 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Active infectious disease. 2. Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhoea. 3. Serious illness, concomitant non-oncological disease or mental problems considered by the investigator to be incompatible with the protocol. 4. Patients with active/symptomatic brain metastases. Patients with a history of treated brain metastases must have stable or normal cerebral MRI scan at screening and be at least three months post-radiation or surgery. 5. Cardiac left ventricular function with resting ejection fraction 26 µmol /L, SI unit equivalent). 9. Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal or greater 5 times the upper limit of normal in case of known liver metastases. 10. Serum creatinine greater than 1.5 mg/dl (>132 µmol/L, SI unit equivalent). 11. Patients who are sexually active and unwilling to use a medically acceptable method of contraception. 12. Pregnancy or breast-feeding. 13. Treatment with other investigational drugs; other anti-cancer-therapy, e.g. chemotherapy, immunotherapy, radiotherapy or hormone therapy (including LHRH agonists, or other hormones taken for breast cancer), concomitantly with therapy on this study and/or during the past four weeks, prior to the first treatment with the trial drug. Treatment with biphosphonates is allowed. 14. Previous treatment with trastuzumab, EGFR-, or EGFR/HER2-inhibitors. 15. Patients unable to comply with the protocol. 16. Active alcohol or drug abuse. 17. Patients who have not recovered from any therapy-related toxicities of previous chemo-, hormone-, immuno-, or radiotherapies at the time of the first administration of the trial drug. 18. Other malignancy within the past 5 years 19. Patients with known pre-existing interstitial lung disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy, safety and pharmacokinetics of BIBW 2992 in two cohorts of patients with HER2-negative breast cancer, after failure of no more than three regimen of prior chemotherapy. Cohort A includes patients with HER2-negative, estrogen- receptor-negative, progesterone-receptor-negative, i.e. triple negative tumours. Cohort B includes patients with HER2-negative, estrogen-receptor-positive and/or progesterone-receptor-positive tumours.;Secondary Objective: Secondary objectives are to look at clinical benefit (CR, PR, SD for a minimum of 4 months), time to objective response, duration of objective response, time to tumour progression, progression-free survival, overall survival, safety of BIBW 2992 as indicated by intensity and incidence of adverse events, graded according to NCI CTCAE version 3.0, especially skin reactions and GI adverse events, cardiac left ventricular function, evaluation of population pharmacokinetics, evaluation of quality of life; ;Primary end point(s): The primary endpoint will be the objective response (CR, PR), determined by RECIST criteria for Cohort B and clinical benefit (CB), i.e. CR, PR and SD for a minimum of 4 months, for Cohort A | — |
Countries
Germany
Outcome results
None listed