Breast cancer
Conditions
Interventions
Chemotherapy with Gemcitabine and Lapatinib combination according to the
following schedule:
Gemcitabine infusion on day 1, 8 and 15 in a cycle of 28 days.
Lapatinib tablets once daily continue day
Sponsors
Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: All patients who are considered for palliative Gemcitabine chemotherapy for advanced breast cancer. Furthermore: 1. > 18 years 2. Performance status: WHO 0 - 2 3. Life expectancy > 3 months 4. Histological or cytological proof of breast cancer 5. Evaluable or measurable disease according to RECIST criteria 6. Previous chemotherapy with an anthracycline and a taxane. 7. Previous Trastuzumab (Herceptin®) in case of Her2/neu overexpression (IHC) or gene amplification (FISH/CISH) 8. No radiotherapy for at least 2 weeks prior to study entry 9. Minimal acceptable safety laboratory values a. ANC of >= 1.5 × 109/l b. Platelet count of >= 100 × 109/l c. Haemoglobin level of >= 10 g/dl (>= 6.2 mmol/l) (prior transfusion is permitted) d. Hepatic function as defined by serum bilirubin = 50 ml/min (by Cockcroft-Gault formula). 10. Cardiac ejection fraction (LVEF) within the institutional range of normal as measured by echocardiogram or MUGA scan (i.e. > 50%). Baseline and on treatment scans should be performed using the same modality. 11. Able to swallow and retain oral medication 12. Written informed consent
Exclusion criteria
Exclusion criteria: 1. More than three previous courses of chemotherapy including adjuvant chemotherapy 2. Patients who have received a cumulative dose of adriamycine more than 360 mg/m2 or a cumulative dose of epirubicine more than 600 mg/m2. 3. Symptomatic CNS metastases. 4. Previous investigational cytotoxic or biological treatment for malignant disease within 30 days before the start of the study. 5. Any treatment with non-oncological investigational drugs within 30 days before the start of the study 6. Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors. 7. Patients using medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of Lapatinib. 8. Treatment within one week before the start of the study with any of the following: terfenadine, cisapride, cyclosporin, tacrolimus, theophylline, diazepam, sulphonylurea hypoglycaemics, phenytoin, or carbamazepine. 9. Uncontrolled infections. 10. All herbal (alternative) medicines are excluded, but multivitamins are allowed. 11. Pregnancy or breast feeding (all women of childbearing potential must have a pregnancy test before inclusion in the study; post-menopausal women must have amenorrhoea for at least 12 months). Female patients must use adequate contraceptive protection. 12. HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with Lapatinib. 13. Clinically significant cardiac impairment or unstable ischaemic heart disease including a myocardial infarction (
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic Measures: Pharmacokinetic parameters (Cmax, Tmax, AUC(inf) en T1/2) will be derived froma plasma concentration versus time data. Tumor Response Outcome Measures: Tumor response will be obtained from all patients with measurable lesions, using the RECIST criteria. The assessments will be made every two cycles (after cycle 2, 4, 6 etc.) or more frequently if indicated. Furthermore, a response is considered confirmed if it is noted on two examinations at least four weeks apart. | — |
Primary
| Measure | Time frame |
|---|---|
| Safety Outcome Measures: Toxicity will be evaluated according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 (van 10 june 2003). Safety assessments will be based on medical review of adverse events reports and the results of vital sign measurements, physical examinations, and clinical laboratory tests throughout the conduct of the study. | — |
Countries
Netherlands
Outcome results
None listed