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Sponsor: GBG Forschungs GmbH
Conditions: Breast Cancer
Interventions: TAC, NX
Primary objective of the study in patients without a sufficient sonographic response (i.e. iNC) to 2 cycles of TAC as preoperative treatment of operable (T\>/= 2cm, N0-2,M0) primary breast cancer: To determine the response rate determined by sonography (iRR = iCR+iPR) of further 4 cycles of docetaxel, doxorubicin and cyclophosphamide (TAC) and of 4 cycles of vinorelbine and capecitabine (NX) (TAC vs. NX) Primary objective of the study in patients with a sufficient sonographic response (i.e. iRR = iPR or iCR) to the first 2 cycles of TAC as preoperative treatment of operable (T\>/=2cm, N0-2,M0) primary breast cancer: To determine the pCR rate of 6 cycles vs. 8 cycles of docetaxel, doxorubicin and cyclophosphamide (TAC x 6 vs. TAC x 8)
Sex: FEMALE
Age: 18 Years to —
Healthy volunteers: No
Study type: INTERVENTIONAL
Inclusion Criteria:
* 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):
* Hematology:
* 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 study.
* 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 indicated.
* 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.
Exclusion Criteria:
* 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 III.
* 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 entry.
* 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 incorporated substances.
* Male patients.