Primary breast cancer, ER or PgR positive, or triple negative and HER-2 negative, larger than 2 cm in diameter. MedDRA version: 14.1 Level: PT Classification code 10057654 Term: Breast cancer female System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: LLT Classification code 10069196 Term: Cytostatic chemotherapy System Organ Class: 100000004865
Conditions
Interventions
Product Name: Cyclophosphamide
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: CYCLOPHOSPHAMIDE
CAS Number: 50-18-0
Concentration unit: mg/m2 milligram(s)/square meter
Conc
Sponsors
Fundación Pública Andaluza para la Gestión de la Investigación en Salud de Sevilla
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Female gender Age ? 18 years Performance Status- ECOG: 0-1 Histologically confirmed invasive breast cancer Primary tumor greater than 2 cm diameter Any N (0-3) No evidence of metastasis (M0), HER-2/ERBb2 negative. Known hormone receptors status. Haematopoietic status: Absolute neutrophil count ? 1.5 x 109/L; Platelet count ? 100 x 109/L; Hemoglobin at least 9 g/dl) Hepatic status: Serum total bilirubin ? 1.5 x upper limit of normal (ULN), in the case of known Gilbert?s syndrome, a higher serum total bilirubin ( 60 ml/m For women of childbearing potential Negative serum pregnancy test, within 2-weeks (preferably 7 days) prior to randomization. Signed informed consent form (ICF). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 165 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 41
Exclusion criteria
Exclusion criteria: Received any prior treatment for primary invasive breast cancer. Previous (less than 10 years) or current history of malignant neoplasms, except for curatively treated: Basal and squamous cell carcinoma of the skin;Carcinoma in situ of the cervix. Diagnosis of inflammatory breast cancer. Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction uncontrolled hypertension (? 180/110), unstable diabetes mellitus, dyspnoea at rest, or chronic therapy with oxygen. Left Ventricular Eyection Fraction of < 50% measured by echocardiography or MUGA. Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject?s safety. Unresolved or unstable, serious adverse events from prior administration of another investigational drug. Active or uncontrolled infection. Dementia, altered mental status, or any psychiatric condition that would prevent the understanding or rendering of ICF. Concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy other than the trial therapies). Concurrent treatment with an investigational agent or participation in another therapeutic clinical trial. Known immediate or delayed hypersensitivity reaction, idiosyncrasy or contraindication to drugs chemically related to any of the study treatments or their excipients. Pregnant or lactating women. Refusal to use contraception throughout the study (surgical sterilization, barrier methods associated with spermicidal gels or total abstinence). Use of hormonal contraceptives is not allowed. Patient unable to comply with study procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate and compare the rate of complete response or pCR (according NSABP guidelines) at the time of surgery in patients with luminal A o B and triple negative (non-Her2/Erb 2 overexpressing and/or amplified) operable breast cancer randomized to standard neoadyuvant chemotherapy (NAC) based in antracyclines versus customized NAC according levels of BRCA1 and ERCC1 mRNA (measured by quantitative RT-PCR).;Secondary Objective: To compare the objective response rate (partial plus complete) among the two arms at definitive surgery. To compare the percent of patients with node-negative disease at surgery among the two treatments arms. To compare the rate of conversion to breast conserving surgery among the two treatments arms. To compare the rate of conversion to breast surgery of patients with non-operable breast cancer among the two arms. To compare disease free survival (DFS) and overall survival (OS). To identify the molecular characteristics of responding tumors by inmunohistochemical, FISH genomic and proteomic analysis.;Primary end point(s): Pathological Complete Response (pCR) is the primary endpoint. Surgical breast and axillary node resection specimens will be evaluated for pathologic tumour response according to NSABP guidelines. Patients will be considered in pCR if there is no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen.;Timepoint(s) of evaluation of this end point: Tumour pCR will be assessed at baseline and after definitive surgery. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Feasibility and type of surgery as indicated by surgeon prior to study treatment. It will be recorded for each patient enrolled at baseline as well as after neoadjuvant treatment period. Percentage of patients with negative axillary nodes at the time of definitive surgery, in both treatment arms. Complete and partial tumor response at the time of surgery. Tumoral response will be assessed by clinical examination and by breast tumor imaging with mammography, ultrasound or MRI, according to the facilities at each site.Overall response (OR) will be assessed using the WHO criteria. Disease free survival (DFS), defined as the time from definitive surgery until disease recurrence. Overall survival (OS), defined as the time from completion of surgery to death from any cause. Identification of molecular characteristics of tumors that are sensitive to therapy, using immunohistochemical analysis of tumor samples (biopsies and resection), as well as in-situ fluorescent hybridization techniques (FISH) in genomics and proteomics.;Timepoint(s) of evaluation of this end point: Each secondary endpoint will be evaluated according to the timepoints set out in the protocol. | — |
Countries
Spain
Contacts
Public ContactUICEC
Hospital Virgen del Rocío
Outcome results
None listed