A Multi-Center Randomized Phase III Study Evaluating 4 Cycles of Docetaxel, Doxorubicin and Cyclophosphamide Versus 4 Cycles of Vinorelbine and Capecitabine in Patients Not Sufficiently Responding to 2 Cycles of TAC and 4 Cycles of TAC Versus 6 Cycles of TAC in Patients Sufficiently Responding to 2 Cycles of TAC as Preoperative Treatment of Locally Advanced or Operable Primary Breast Cancer
- Written informed consent must be obtained and documented according to the local
regulatory requirements prior to beginning specific protocol procedures.
- Complete baseline documentation sent to SKM CRS.
- Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by
core biopsy. Fine-needle aspiration is not sufficient. Incisional biopsy is not
allowed. In case of bilateral cancer the investigator has to decide prospectively
which side will be evaluated for the primary endpoint.
- Tumor lesion in the breast with a palpable size of > 2 cm in maximum diameter. The
leasion has to be measurable in two-dimensions by sonography. In case of inflammatory
disease the extent of inflammation can be used as measurable lesion. The following
tumor stages are eligible:
- Palpable breast tumor size of > 2 cm without involvement of the skin or muscle
or evidence of inflammatory disease (T2-3). Clinical N0-2. (Study population I)
- Primary tumor with clinical involvement of skin or muscle or clinically evidence
of inflammatory breast cancer (T4 a-d) or clinical N3 including supraclavicular
nodes. (Study population II). In patients with multifocal or multicentric breast
cancer, the largest lesion should be measured.
- Age > 18 years.
- Karnofsky Performance status index > 80%.
- Normal cardiac function must be confirmed by LVEF or shortening fraction
(echocardiography or MUGA scan respectively) within 3 months prior to registration.
The result must be above the normal limit of the institution.
- Laboratory requirements (within 14 days prior to registration):
- Neutrophils > 2.0 x 109/L and
- Platelets > 100 x 109/L and
- Hemoglobin > 10 g/dL
- Hepatic function:
- Total bilirubin < 1 x UNL and
- ASAT (SGOT) and ALAT (SGPT) < 2.5 x UNL and
- Alkaline phosphatase < 5 UNL. Patients with ASAT and/or ALAT > 1.5 x UNL
associated with alkaline phosphatase > 2.5 x UNL are not eligible for the
- Renal function:
- Creatinine < 175 µmol/L (2 mg/dL)
- Tissue block centrally available for further biological tests.
- Negative pregnancy test (urine or serum) within 14 days prior to registration for all
women of childbearing potential.
- Complete staging work-up within 3 months prior to registration. All patients must
have bilateral mammography, breast ultrasound, breast MRI (optional), chest X-ray (PA
and lateral), abdominal ultrasound and/or CT scan, and bone scan. In case of positive
bone scan, bone X-ray is mandatory. Other tests may be performed as clinically
- Patients must be available and compliant for treatment and follow-up. Patients
registered on this trial must be treated and followed up at the participating center
which can be the Principal or the Co- Investigator's site.
- Early breast cancer with a tumor size of < 2 cm measured by palpation.
- Patients with low or moderate risk. These patients are defined as having none of the
following risk factors: Age < 36 years, cT> 5cm, ER and PR negative, cN+, or Grade
- Evidence of distant metastasis.
- Prior chemotherapy for any malignancy.
- Pregnant or lactating patients. Patients of childbearing potential must implement
adequate non-hormonal contraceptive measures during study treatment.
- Pre-existing motor or sensory neuropathy of a severity > grade 2 by NCI criteria.
- Other serious illness or medical condition:
- previous malignant disease with a disease-free survival of less than 5 years
(except CIS of the Cervix and non-melanomatous skin cancer.
- congestive heart failure or unstable angina pectoris, previous history of
myocardial infarction within 1 year prior to study entry, uncontrolled arterial
hypertension or high-risk uncontrolled arrhythmias.
- history of significant neurologic or psychiatric disorders including psychotic
disorders, dementia or seizures that would prohibit the understanding and giving
of informed consent.
- active uncontrolled infection.
- active peptic ulcer, unstable diabetes mellitus.
- Chronic treatment with corticosteroids unless initiated > 6 months prior to study
entry and at low dose (= 20 mg methylprednisolone or equivalent).
- Concurrent treatment with sex hormones. Prior treatment must be stopped before study
- Definite contraindications for the use of corticosteroids.
- Concurrent treatment with other experimental drugs. Participation in another clinical
trial with any investigational not marketed drug within 30 days prior to study entry.
- Concurrent treatment with any other anti-cancer therapy.
- Known hypersensitivity reaction to one of the investigational compounds or
- Male patients.