a prospective, multicenter, open-label 12 week neoadjuvant phase ii trial optimizing taxane therapy in elderly patients with low response

Conditions: Early Primary Breast Cancer

Summary: comparison of pre-surgical myocet/ cyclophosphamide (mc) q3w followed by either mc or paclitaxel - depending on early response assessment by ultrasound or by toxicity for elderly non frail primary breast cancer patients with increased risk of relapse.


Eligibility criteria:
general inclusion criteria for adapt: * female patients, age at diagnosis 18 years and above (consider patients at 70 years and above for adapt elderly) * candidate for chemotherapy on the basis of conventional criteria * histologically confirmed unilateral primary invasive carcinoma of the breast * clinical t1 - t4a-c * all clinical n (cn) * no clinical evidence for distant metastasis (m0) * known hr status and her2 status (local pathology) * tumor block available for central pathology review * performance status ecog \ = 80% * written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements * the patient must be accessible for treatment and follow-up * patients must qualify for neoadjuvant treatment * lvef \> 50%; lvef within normal limits of each institution measured by echocardiography and normal ecg (within 42 days prior to chemotherapy) * laboratory requirements : * leucocytes ≥ 3.5 x 109/l * platelets ≥ 100 x 109/l * hemoglobin ≥ 10 g/dl * total bilirubin ≤ 1 x uln * asat (sgot) and alat (sgpt) ≤ 2.5 x unl * creatinine ≤ 175 µmol/l (2 mg/dl) additional inclusion criteria adapt elderly: * ≥ 70 years old * charlson scale ≤ 2 * hr+/her2- disease: if rs and sequential testing are available n0-1/rs 12-25/poor response or n0-1/rs ≥26 * all g3 with ki-67 ≥40% in tumors \>1cm * all n2 * all tn * all subtypes general exclusion criteria for adapt: * known hypersensitivity reaction to the compounds or incorporated substances * prior malignancy with a disease-free survival of \< 10 years, except curatively treated basalioma of the skin, ptis of the cervix uteri * non-operable breast cancer including inflammatory breast cancer * previous or concurrent treatment with cytotoxic agents for any reason after consultation with the sponsor * 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 participation in non-interventional post authorization safety studies not influencing the primary study endpoints is allowed, e.g. wsg protroca for evaluation of primary/secondary g-csf prophylaxis) * male breast cancer * sequential breast cancer * reasons indicating risk of poor compliance * patient not able to consent additional exclusion criteria adapt elderly: * known polyneuropathy ≥ grade 2 * severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study * inadequate organ function (e.g. hepatic impairment, pulmonary disease, etc.) * uncompensated cardiac function (current unstable ventricular arrhythmia requiring treatment, history of symptomatic chf nyha classes ii-iv), history of myocardial infarction or unstable angina pectoris within 12 months of enrollment, history of severe hypertension, cad - coronary artery disease) * severe dyspnea * pneumonitis * abnormal blood values: * thrombocytopenia \> ctcae grade 1 * increases in alt/ast \> ctcae grade 1 * hypokalaemia \> ctcae grade 1 * neutropenia \> ctcae grade 1 * anaemia \> ctcae grade 1

Keywords: breast cancer elderly