A Phase I/II Study of Lapatinib Plus Myocet TM in Patients With HER2+ve Metastatic Breast Cancer Following Disease Progression During, or After, Treatment With Trastuzumab and Taxanes
1. Written informed consent obtained prior to any study-related procedures.
2. Female patients, age ≥ 18 years, who are either post menopausal (post-menopausal
status will be defined as patients who are amenorrheic for > 1 year or for a shorter
duration if FSH, LH and/or oestradiol levels are within the post-menopausal range),
surgically sterile or practicing an effective method of birth control agreed with the
patients study physician. Women of childbearing potential should use an effective
contraceptive ( such as non hormonal intra uterine device (IUD), condoms, sexual
abstinence or vasectomised partner).during treatment and up to 6 months following
discontinuation of therapy.
3. Histologically confirmed metastatic breast cancer
4. Documented HER2 overexpression (IHC 3+ or FISH or CISH positive)
5. At least one measurable lesion according to RECIST criteria. Patients with bone only
disease are not eligible.
6. Patients with controlled brain metastasis are eligible.
7. Documented disease progression. Progression for entry is defined as appearance of any
new lesion not previously identified or increase of 25% or more in existent lesion
from previous CT scan and must be documented
8. Prior treatment must have contained trastuzumab and taxane. Patients may have been
treated with Lapatinib previously.
9. Life expectancy of at least 12 weeks
10. ECOG Performance Status of ≤ 2
11. Left ventricular ejection fraction (LVEF) ≥ 55%, as measured by Echocardiogram or
MUGA Scan (within 14 days prior to first infusion), and no documented history of
uncontrolled or symptomatic angina, arrhythmias or congestive heart failure within
the previous 6 months
12. Adequate bone marrow, haematological, hepatic and renal function defined as:
- Absolute Neutrophils Count ≥ 1.5 x 109/L
- Platelet Count ≥ 100 x 109/L
- Haemoglobin ≥ 9.0 g/dL
- Calculated creatinine clearance ≥ 40 mL/min
- Total bilirubin ≤ ULN. Patients with Gilbert's syndrome prior to study entry
must have total bilirubin < 3 x ULN.
- Alkaline Phosphatase and AST or ALT within the parameters specified in protocol
13. Patients must have recovered from clinically significant side effects associated with
prior radiotherapy and chemotherapy
14. Able to swallow and retain oral medication.
15. Formalin-fixed paraffin-embedded tissue from archived tumour tissue samples available
(from the primary or metastatic tissue.
Patients meeting any of the following exclusion criteria are not eligible for enrolment
into this study:
1. Pregnant or lactating women
2. Prior anthracycline chemotherapy with a lifetime dose exceeding 360 mg/m2 doxorubicin
or 550 mg/m2 epirubicin
3. Documented history of poorly controlled hypertension), arrhythmia, clinically
significant valvular disease, angina requiring treatment, transmural infarction,
myocardial infarction within the previous 6 months
4. Concurrent disease that would make the patient inappropriate for study participation,
or any other serious medical disorder that would interfere with the patient's safety
5. Dementia, altered mental status, or any other psychiatric condition that would
interfere with the patient's safety or informed consent
6. Active or uncontrolled bacterial, viral or fungal infection.
7. History of other malignancy. However patients who have been disease free for 5 years,
or patients with a history of resected non-melanoma skin cancer or successfully
treated in situ cancer are eligible
8. Concurrent cancer therapy (chemotherapy, immunotherapy, biologic therapy, hormonal
therapy, or within 4 weeks preceding the first dose of investigational product)
9. Unresolved or unstable, serious toxicity from prior administration of another
10. Concurrent treatment with an investigational drug within 4 weeks preceding the first
dose of investigational product
11. Known hypersensitivity to lapatinib and Myocet™ or their excipients
12. Any other contraindications for lapatinib and Myocet™
13. Receive concurrent treatment with prohibited medications. Zometa for patients with
bone metastasis is allowed. If the patient is on Zometa at start of the study, it
should be continued throughout the duration of the study.