Phase I study of Gemcitabine plus Lapatinib (GW572016) in women with advanced breast cancer
- Conditions
- Breast cancer10006291
- Registration Number
- NL-OMON30513
- Lead Sponsor
- Antoni van Leeuwenhoek Ziekenhuis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 25
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 <= 1.5 times the upper limit of normal, ALT and AST <= 2.5 times the upper limit of normal.
e. Renal function as defined by serum creatinine <= 1.5 times upper limit of normal or creatinine clearance >= 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
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 (< 3 months of study entry)
14. History of alcoholism, drug addiction, or any psychiatric or psychological condition which in the opinion of the investigator would impair study compliance
15. Malabsorption syndrome or other condition which may affect absorption of Lapatinib.
16. Concurrent or previous malignancy of a different tumour type within five years of starting the study except for adequately treated non-melanoma skin cancer or cervical intraepithelial neoplasia
17. Patients who have had previous treatment with Lapatinib.
18. Legal incapacity
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Safety Outcome Measures: Toxicity will be evaluated according to the NCI Common<br /><br>Terminology Criteria for Adverse Events (CTCAE) v3.0 (van 10 june 2003). Safety<br /><br>assessments will be based on medical review of adverse events reports and the<br /><br>results of vital sign measurements, physical examinations, and clinical<br /><br>laboratory tests throughout the conduct of the study.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Pharmacokinetic Measures: Pharmacokinetic parameters (Cmax, Tmax, AUC(inf) en<br /><br>T1/2) will be derived froma plasma concentration versus time data.<br /><br>Tumor Response Outcome Measures: Tumor response will be obtained from all<br /><br>patients with measurable lesions, using the RECIST criteria. The assessments<br /><br>will be made every two cycles (after cycle 2, 4, 6 etc.) or more frequently if<br /><br>indicated. Furthermore, a response is considered confirmed if it is noted on<br /><br>two examinations at least four weeks apart.</p><br>