Breast cancer is the most common form of cancer among women in North America, Europe and Latin America. Beacause nearly 80% of breast cancers are endocrine-responsive tumors, the majority of patients candidates for adjuvant chemotherapy (CT) are also candidates for endocrine therapy (ET).The optimal timing (i.e. concomitant vs sequential administration) for the integration of these two treatments has not been clearly defined yet.
Conditions
Interventions
Trade Name: ARIMIDEX*28CPR RIV 1 MG
Product Name: ANASTROZOLO
Product Code: NA
Pharmaceutical Form: Capsule
Trade Name: LETROZOLE 2.5 MG TABLETS
Product Name: LETROZOLO
Product Code: NA
Pharmaceutica
Sponsors
IRCCS AOU SAN MARTINO- IST
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Women with histological diagnosis of invasive breast cancer completely removed by surgery, any T, any N. - Postmenopausal status defined by at least one of the following conditions: 1. Aged = 60 2. Aged 45-59 and satisfying one or more of the following criteria • amenorrhea for =12 months and intact uterus; • amenorrhea for 18 years. - Primary tumor positive for ER and/or PgR (=1% tumor cells positive by immunohistochemistry or = 10 fmol/mg cytosol protein by ligand binding assay). - Patients who are prescribed 5 years of endocrine therapy with an AI - Indication for adjuvant chemotherapy- Patients with HER-2 positive tumors are eligible provided that they are prescribed trastuzumab according to registered schedule. - Signed informed consent. 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 1200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 600
Exclusion criteria
Exclusion criteria: - HRT currently assumed or during the month before randomization - Recurrent or metastatic disease - HER-2 positive tumors if treatment with trastuzumab is considered not appropriate/feasible - Concurrent illness that contraindicate adjuvant endocrine treatment and/or chemotherapy - Patients who have received TAM as part of any breast cancer prevention trial - Previous history of invasive breast cancer or other invasive malignancy within the previous 10 years, other than squamous or basal cell carcinoma of the skin or carcinoma in situ of the cervix, adequately cone biopsied - Concomitant severe disease which would place the patient at unusual risk - Concurrent treatment with experimental drugs - Patients treated with systemic investigational drugs within the past 30 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the relative efficacy of sequential as compared to concurrent administration of chemotherapy and aromatase inhibitors in patients with early breast cancer in the prevention of disease recurrence.;Secondary Objective: To evaluate the relative efficacy of the two treatment strategies on overall mortality, local relapses, distant relapses, and to compare their toxicity.;Primary end point(s): According to the STEEP system (Hudis et al. J Clin Oncol 2007; 25:2127-2132) the primary endpoint will be the so called DFS, defined as time elapsing between the date of randomization and the date of one of the following events, whichever occurs first ?? Local Recurrence of disease ?? Regional recurrence of disease ?? Distant recurrence of disease ?? Contralateral invasive or intraductal breast cancer ?? Second primary malignancy other than breast ?? Death for any cause ;Timepoint(s) of evaluation of this end point: The study hypothesis is that concurrent administration of chemotherapy and endocrine therapy will be associated with a 20% relative reduction in the hazard of recurrence, with a 7% absolute increase in 10-year DFS, which is estimated to be 50% in the control group. For a type I error level of .05 (two sided) and 80% power, it is necessary to observe 635 events. To this aim, 900 patients per arm will be recruited over a 3-year period (a total of 1800 patients), for a recruitment rate of 600 subjects per year, which is considered feasible. No interim analyses will be performed; the final analysis will be conducted when 635 events have been observed, presumably after 5.5 years of follow-up. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints will be: - the Overall Survival (OS) defined as time elapsing between the date of randomization and the date of death for any cause - all the other outcomes defined within the STEEP system (i.e. IDFS, DDFS, DRFS, RFS, Recurrence-free interval, Breast cancer-free interval, Distant recurrence-free interval – as reported in: Hudis et al. J Clin Oncol 2007; 25:2127-2132). -safety: clinical and laboratory toxicities will be graded according to NCI criteria CTCAE (Common Terminology Criteria for Adverse Events of National Cancer Institute v.4.02). The adverse events witch are not reported in NCI criteria will be graded as: mild (1), moderate (2), severe (3), and life threatening (4).;Timepoint(s) of evaluation of this end point: See timepoints of evaluation for primary endpoint | — |
Countries
Italy
Contacts
Public ContactSEGRETERIA DEL COMITATO ETICO
IRCCS AOU SAN MARTINO- IST
Outcome results
None listed