Docetaxel, Doxorubicin and Cyclophosphamide Versus Vinorelbine and Capecitabine in Patients Not Sufficiently / Sufficiently Responding as Preoperative Treatment of Locally Advanced or Operable Primary Breast Cancer (GeparTrio)

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.