Clinical trial NCT02181101 (phase 3, status: completed)
Conditions: breast neoplasms
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: fec-docgemzar adjuvant chemotherapy, fec-doc adjuvant chemotherapy, zoledronic acid i.v. 2 years, zoledronic acid i.v. 5 years
SMILES: [H][C@@]12N(C)C3=CC(OC)=C(C=C3[C@@]11CCN3CC=C[C@](CC)([C@@]13[H])[C@@]([H])(OC(C)=O)[C@]2(O)C(=O)OC)[C@]1(C[C@@]2([H])CN(CC(CC)=C2)CC2=C1NC1=CC=CC=C21)C(=O)OC, [H][C@@]12N(C)C3=CC(OC)=C(C=C3[C@@]11CCN3CC=C[C@](CC)([C@@]13[H])[C@@]([H])(OC(C)=O)[C@]2(O)C(=O)OC)[C@]1(C[C@@]2([H])CN(CC(CC)=C2)CC2=C1NC1=CC=CC=C21)C(=O)OC
Eligibility criteria:

        Inclusion Criteria:

          -  Primary epithelial invasive carcinoma of the breast pT1-4, pM0

          -  Histopathological proof of axillary lymph node metastases (pN1-3) or high risk pN0/NX,
             defined as: 'pT ≥ 2 or histopathological grade 3 or age ≤ 35 or negative hormone
             receptor status'

          -  Complete resection the primary tumor with margins of resection free of invasive
             carcinoma not more than 6 weeks ago

          -  Females ≥ 18 years of age

          -  Performance Status ≤ 2 on Eastern Cooperative Oncology Group (ECOG) Scale

          -  Adequate bone marrow reserve: leucocytes ≥ 3.0 x 10^9/l and platelets ≥ 100 x 10^9/l

          -  Bilirubin within one fold of the reference laboratory's normal range, aspartate
             aminotransferase (ASAT) (serum glutamate oxalacetate transaminase, SGOT), alanine
             aminotransferase (ALAT) (serum glutamate pyruvate transaminase, SGPT) and alkaline
             phosphatase (AP) within 1,5 fold of the reference laboratory's normal range for
             patients

          -  Intention of regular follow-up visits for the duration of the study

          -  Ability to understand the nature of the study and to give written informed consent

        Exclusion Criteria:

          -  Inflammatory breast cancer

          -  Previous or concomitant cytotoxic or other systemic antineoplastic treatment which is
             not part of or allowed within this study

          -  History of treatment or disease affecting bone metabolism (e.g., Paget's disease,
             primary hyperparathyroidism)

          -  Prior treatment with bisphosphonates within the last 6 months

          -  Severe renal insufficiency as evidenced by creatinine clearance < 30 ml/min as
             calculated using the Cockcroft-Gault formula

          -  Second primary malignancy (except in situ carcinoma of the cervix or adequately
             treated basal cell carcinoma of the skin)

          -  Cardiomyopathy with impaired ventricular function (New York Heart Association
             Functional Classification Class (NYHA) > II), cardiac arrythmias influencing left
             ventricular ejection fraction (LVEF) and requiring medication, history of myocardial
             infarction or angina pectoris within the last 6 months, or arterial hypertension not
             being controlled by medication

          -  Any known hypersensitivity against docetaxel, epirubicin, cyclophosphamide,
             fluorouracil, gemcitabine or any other medication included in the study protocol

          -  Use of any investigational agent within 3 weeks prior to inclusion

          -  Patients in pregnancy or breast feeding (in premenopausal women anticonception has to
             be assured: intra uterine devices, surgical methods of sterilization, or, in hormone
             unsensitive tumors only, oral, subcutaneous or transvaginal hormonal, non estrogen
             containing contraceptives)

          -  Current active dental problems including infection of the teeth or jawbone (maxilla or
             mandibular); dental or fixture trauma, or a current or prior diagnosis of
             osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after
             dental procedures.

          -  Recent (within 6 weeks) or planned dental or jaw surgery (e.g.. extraction, implants)