Lymph-node negative early breast cancer and breast cancer with 1 to 3 positive nodes MedDRA version: 20.0 Level: PT Classification code 10057654 Term: Breast cancer female System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
European Organisation for Research and Treatment of Cancer
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Women with histologically proven operable invasive breast cancer with 0 to 3 positive lymph nodes and no distant metastases. Acceptable treatment options are: •Breast conserving surgery or mastectomy with either a sentinel node procedure or full axillary clearance. •Radiotherapy is mandatory in the case of breast conserving surgery and will be administered according to local institutional policy after mastectomy. •patients with unresectable positive deep margins who will receive adjuvant radiotherapy are eligible provided that all other margins are negative. •With a clinical tumor classification of T1, T2 or operable T3. •The breast tumor must be unilateral. Multifocal tumours are allowed provided that they have identical histology. DCIS or LCIS are allowed if invasive cancer is present. •A frozen tumor sample (not fixed in formalin) must be available for inclusion. The tumor sample must be a core punch biopsy taken from the excised primary tumor. •Patients should be aged = 18 years at randomization •Have a WHO performance status of 0 or 1. •have adequate bone marrow reserves (neutrophil count >1.5 x109 /l and platelet count >100 x109/l), adequate renal function (serum creatinine = 1.5 x upper limit of normal) and hepatic function (ALAT, ASAT = 2.5 x upper limit of normal, alkaline phosphatase = 2.5 x upper limit of normal and total bilirubin = 2.0 x upper limit of normal) •have no serious cardiac illness or medical condition including but not confined to: a history of documented congestive heart failure (CHF), high-risk uncontrolled arrhythmias, angina pectoris requiring antianginal medication, clinically significant valvular heart disease, evidence of transmural infarction on ECG, poorly controlled hypertension (e.g. systolic > 180 mm Hg or diastolic > 100 mm Hg), symptomatic coronary artery disease or a myocardial infarction within the last 12 months or other risk factors that contra-indicate the use of anthracycline-based chemotherapy. •while taking study medications patients should take adequate birth control measures such as highly effective methods as defined by the Note 3 of the note for guidance on non-clinical safety studies for the conduct of human clinical trials for pharmaceuticals (CPMP/ICH/286/95): “A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less then 1% per year) when used consistently and correctly such as implants, injectables, some IUDs, condoms, sexual abstinence or vasectomised partner. •Signed written informed consent must be given according to ICH GCP, and national/local regulations before enrollment in the trial (Both the screening PIS & IC and PIS & IC 1 must be signed before enrollment). 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 6600 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Have serious uncontrolled intercurrent infections, or other serious uncontrolled concomitant disease. • have previous or concurrent cancer, possible exceptions are; adequately treated carcinoma in situ of the cervix, non-melanoma skin cancer, lobular or ductal carcioma in situ of the breast and any invasive cancer (other than breast cancer) in complete remission for = 5 years. • have received (neo) adjuvant chemotherapy, (neo) adjuvant endocrine therapy or radiotherapy for the primary breast cancer considered for this trial. • Have participated in any investigational drug study within the 4 weeks preceding the start of treatment. • Be pregnant or lactating at the time of diagnosis or randomization. A woman of childbearing potential must have a negative pregnancy test. If post-menopausal, the woman must have been amenorrheic for at lest 12 months to be considered of non-childbearing potential • Have any psychological, familial, sociological, geographical or serious uncontrolled medical (e.g. a history of uncontrolled seizures, central nervous system disorders, or psychiatric disability) condition judged by the investigator to be clinically significant which could potentially preclude informed consent or interfere with compliance for oral drug intake or with the study protocol and follow-up schedule. These conditions should be discussed with the patient before registration in the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. The primary objective of the MINDACT trial is to demonstrate the superiority of the molecular profiling approach over the usual clinical assessment in assigning adequate risk categories (and the need to receive adjuvant chemotherapy or not) to breast cancer patients with 0 to 3 positive nodes. 2. The trial will also aim to compare a docetaxel-capecitabine regimen possibly associated with increased efficacy and reduced long-term toxicities to existing commonly used anthracycline-based chemotherapy regimens (anthracyclines followed by docetaxel for node positive). 3. Finally to determine the best endocrine treatment strategy i.e. single agent up-front, aromatase inhibitor (AI) (letrozole) for seven years compared to the sequential endocrine strategy of 2 years of tamoxifen followed by 5 years of letrozole. ;Secondary Objective: Estimation of disease free survival, distant metastasis free survival, overall survival of chemotherapy in the groups where the prognostic methods are discordant Calculation of overall estimates of efficacy for each treatment strategy according to the prognostic methods Estimation of the % of patients receiving chemotherapy per each prognostic method To identify and/or validate predictive gene expression profiles of clinical response/resistance to anthracycline and docetaxel-capecitabine chemotherapy, and novel gene expression signatures predicting clinical response to sequential tamoxifen-AI versus AI alone To compare the OS distributions associated with the 2 chemotherapy arms To determine and compare early and late toxicities associated with each arm To evaluate adjuvant endocrine treatment success or failure in the group of postmenopausal patients with endocrine responsive disease To compare the safety profile of the two endocrine therapy regimens;Primary end point(s): Treatment decision randomization (R-T) The primary endpoint for the treatment decision randomization is distant metastasis free survival (DMFS) at 5 yea | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Treatment decision randomization (R-T) - the proportion of women treated with chemotherapy per treatment decision making tool i.e. clinical prognosis compared to 70-gene signature prognosis - overall survival at 5 years - DFS at 5 years Chemotherapy randomization (R-C) - overall survival at 5 years - safety both early and late - DMFS at 5 years Endocrine therapy randomization (R-E) - overall survival at 5 years - DMFS at 5 years;Timepoint(s) of evaluation of this end point: Cf section E5.2 | — |
Countries
Belgium, France, Germany, Italy, Netherlands, Poland, Portugal, Slovenia, Spain, Switzerland, United Kingdom
Contacts
Public ContactClinical Operations Department
European Organisation for Research and Treatment of Cancer (EORTC)
Outcome results
None listed