A Phase II Randomised, Multicentre Compare Epirubicine and Cyclophosphamide Treatment Plus Docetaxel and Trastuzumab Versus Epirubicine and Cyclophosphamide Treatment Plus Docetaxel and Lapatinib in Women With Primary Resectable Breast Cancer or Locally Advanced Breast Cancer Positive Her 2.
1. Signature of the written informed consent.
2. Histological documentation of breast cancer.
3. Stage I (T1, N0M0), IIA (T2N0M0); IIB (T2N1M0, T3N0M0), IIIA (TXN2M0) and IIIB
(T3N1M0, T4NXM0) primary resectable breast cancer or locally advanced breast cancer.
4. HER2-positive breast cancer, defined as IHC 3+ or positive FISH. When IHC 2+ HER2
status must be assessed by FISH.
5. The patient granted her consent for taking a biopsy before treatment
6. The patient granted her consent for sending two tumor samples to central laboratory
for molecular sub study.
7. Two weeks prior randomization pregnancy test negative for women of childbearing
8. Women of childbearing potential must use adequate contraceptive measures during
participation into study. Oral, injectable or implant hormonal contraceptives measure
are not permitted.
9. A WHO performance status of 0 or 1 ( Karnofsky ³ 80)
10. Age > 18 years.
11. Absence of metastases disease
12. Baseline EKG 12 weeks prior to randomization. Baseline LVEF value within limit of
normal value for the institution or > 50% of basal value
13. Normal laboratory test 2 weeks prior to randomization Haematology values: Neutrophil
count ≥ 1,5 x109/l; Platelets ≥ 100 x 109/l; Haemoglobine ≥ 10mg/dl
Biochemistry values: serum total bilirubin £ 1 ULN; ASAT (SGOT) y ALAT (SGPT) £ 2,5
ULN; alkaline phosphatase £ 5 ULN. The patients which ASAT and/or ALAT value are >
1,5 ULN along with alkaline phosphatase value > 2,5 ULN will be not included into the
Renal function: serum creatinine £ 175 µmol/l (2 mg/dl). If the value are borderline,
clearance creatinine must be ≥ 60 ml/min
14. 12 weeks prior to randomization the following assessments and procedures must be
fulfilled: Bilateral mammography; MRI Breast and axillary; Chest X-Ray (PA and
lateral); Abdominal ultrasound; Chest CT-Scan; Abdominal CT-Scan. Bone Scan (if
15. Patients must be accessible for treatment and follow up
1. Patients with lumpectomy, partial mastectomy, modified radical mastectomy are not
allowed to include into study.
2. Prior Immunotherapy, hormonal therapy and chemotherapy for breast cancer is not
3. Prior therapy with anthracycline and taxanes ( paclitaxel and docetaxel) is not
permitted for any neoplasia.
4. Prior radiotherapy for breast cancer.
5. Bilateral invasive breast carcinoma
6. Pregnant or nursing patients. Negative pregnant test ( serum or urine) 14 days prior
7. HER 2 negative breast cancer
8. Patients of childbearing potential must be use adequate contraceptive measures during
study treatment. No hormonal contraceptive measure is permitted.
9. Any M1 breast cancer
10. Any motor or sensorial neurotoxicity grade ≥ 2 according to CTC criteria version 3.
11. Serious cardiac illness or medical conditions: Congestive heart failure, angina
pectoris requiring specific treatment, myocardial infarction 1 year prior to enroll
in the study; poorly controlled hypertension or high-risk uncontrolled arrhythmias.
History of significative neurological or psychiatric disease ( psychotic, dementia or
attack ) what is unable to patient to grant her informed consent.
Uncontrolled severe Infection Uncontrolled diabetes mellitus, active peptic ulcer
12. Current malignancy or previous malignancy other that breast cancer. Exception cell
carcinoma of the skin no melanoma, carcinoma in situ of the cervix or any other
cancer in the past 10 years.
13. Long term treatment with corticoids except 6 months prior to inclusion in the study
and low doses ( £ 20 mg metilprednisolone or equivalent )
14. Corticoid use contraindication
15. Concomitant hormonal replacement therapy. Previous treatment should be interrupted
before inclusion into study.
16. Cardiopathy what stops patient taking Docetaxel and Herceptin: myocardial infarction
recorded; angina pectoris requiring specific treatment; any congestive heart failure
recorded; arrhythmia grade 3 or 4 according to CTC ver.3; any relevant valvular
disease; chest X ray which shows cardiomegaly or EKG which shows ventricular
hypertrophy unless FEVI value has been upper URL in the last 3 months.
17. Poorly controlled hypertension ( systolic > 180 mm Hg or diastolic > 100 mm Hg). The
patients with controlled hypertension under treatment can be included into study
18. Patients under treatment of arrhythmia, angina or congestive heart failure with drug
which modifies cardiac conduction (after digital, beta blocker or inhibitors calcium
channel) are excluded. However if these drugs are took for arterial tension the
patient can be included into study.
19. The patient must interrupt concomitant treatment with hormonal therapy ej. raloxifen,
tamoxifen and selective estrogen receptor modulators (SERM) prior to randomization.
20. Concomitant use of inhibitors and inductors of enzyme CYP3A4 complex ( ketoconazol,
itraconazol or grape juice; rifampicin, carbamazepin or fenitoin ) are not permitted.
Also, drug are substrate of enzyme CYP2C8 complex is not permitted along with
21. Concurrent treatment with an investigational agent or participation in another
therapeutic clinical trial within 30 days prior to randomization into study.
22. Concomitant treatment with other anticancer therapy
23. Hypersensitivity reaction to drugs herceptin, lapatinib or their excipients.