Adjuvant Chemotherapy for Elderly Non Frail Patients With an Increased Risk for Relapse of a Primary Carcinoma of the Breast

Primary Objective:

Phase II:

To determine the compliance and safety of epirubicin plus cyclophosphamide or CMF (EC/CMF) and nab-paclitaxel in combination with capecitabine (PX).

Secondary Objective(s):

• To compare the disease-free survival (DFS) and distant disease free survival (DDFS) with epirubicin plus cyclophosphamide or CMF (EC/CMF) vs. nab-paclitaxel in combination with capecitabine (PX).
• To compare the overall survival (OS) with epirubicin plus cyclophosphamide or CMF (EC/CMF) vs nab-paclitaxel in combination with capecitabine (PX).
• To analyze the efficacy of treatments in subgroups according to clinical stratification factors.
• To determine prognostic factors on tumor tissue collected from primary surgery and to correlate them with study treatment effect.
• To compare the geriatric assessments scores (Charlson, VES-13, IADL, G8) at baseline and end of therapy.

Inclusion criteria

• Written informed consent for all study procedures must be obtained and documented according to local regulatory requirements prior to beginning specific protocol procedures.
• Complete baseline documentation must be sent to GBG Forschungs GmbH.
• Histological confirmed unilateral or bilateral primary carcinoma of the breast.
• Female and male breast cancer patients with age at first histologically diagnosis and axilla dissection ≥ 65 years.
• Adequate surgical treatment with complete resection (R0) of the tumor and ≥ 10 axillary nodes. Sole sentinel node biopsy is allowed if the sentinel node shows no tumor involvement.
• No evidence for distant metastasis at bone scan, liver ultrasound and chest x-ray.
• Patients with stage pT3/4 or pN2/3 (≥ 4 involved lymph nodes) irrespective of additional risk factors.
• Patients with stage pT1/2 and pN0/1 (0-3 involved lymph nodes) with an increased risk according to the clinico-pathological or uPA/PAI-1 criteria.
• ECOG Performance Status <= 2.
• Charlson Scale <= 2.
• Estimated life expectancy of at least 5 years (irrespective of breast cancer diagnosis).
• The patient must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre which could be the Principal or a Co- investigator's site.

Exclusion criteria

• Known hypersensitivity reaction to the compounds or incorporated substances or known dihydropyrimidine dehydrogenase deficiency.
• Low risk patient according to risk assessment.
• Inadequate organ function including:

Leucocytes < 3,5 G/l, Platelets < 100 G/l , Creatinine or Bilirubin above normal limits (1,25 above upper normal limit), Creatinine-Clearance below 50 ml/min, uncompensated cardiac function, severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study.

• Previously or currently one of the following medical conditions:

• pre-existing motor or sensory neuropathy of a severity >= grade 2 by NCI-CTC criteria;
• history of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent;
• known or suspected congestive heart failure (> NYHA I) and/or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, un- or poorly controlled arterial hypertension (i.e. BP >150/100 mmHg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease;
• Creatinine Clearance less than 50 ml/min;
• another primary malignancy with an event-free survival of < 5 years, except curatively treated basalioma of the skin and carcinoma in situ of the cervix.
• Time since axillary dissection > 3 months.
• Locally advanced, non-operable breast cancer.
• Previous invasive breast carcinoma.
• Prior chemotherapy for any malignancy.
• Concurrent specific systemic anti-tumor treatment or treatment with experimental compounds within the last 6 months.
• Concurrent treatment with other tumor specific experimental drugs. Participation in another clinical trial with any investigational not marketed drug.
• Concurrent treatment with virostatic agents like sorivudine or analogues like brivudine, concurrent treatment with aminoglycosides, anticoagulants: heparin, warfarin as well as acetylic acid (e.g. Aspirin®) at a dose of > 325mg/day or clopidogrel at a dose of > 75 mg/day).