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

• Status: Completed
• Trial end date: 2008-02-01
• Target enrollment: 0
• Participant gender: Female

Summary

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)

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: German Breast Group
• Collaborators: Amgen; Roche Pharma AG; Sanofi; University Hospital, Frankfurt
• Treatments: Capecitabine; Cyclophosphamide; Docetaxel; Doxorubicin; Liposomal doxorubicin; Vinorelbine

Criteria

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 (
• 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.