This is an adjuvant, open, prospective, randomized study to compare: A. Individually tailored and two weekly dosed epirubicin + cyclophosphamide followed by a three weeks break followed by biweekly and tailored docetaxel (dtEC→dtT) given every second week, to B. Fixed dosed and three weekly epirubicin, cyclophosphamide and 5-fluorouracil, followed by fixed dosed and three weekly docetaxel (FEC→T). Patients with primary node-positive or high risk lymph node negative breast cancer will be eligible for the study. The primary objective of the phase 3 study is to compare breast cancer relapse-free survival (BCRFS) between the dtEC→dtT and FE100C→T. To detect a five-year BCRFS difference of 0.710 to 0.790 about 1000 patients per arm will be needed. They will be recruited during four years and followed another two years for breast cancer events. Secondary objectives are to compare 1. Distant disease-free survival (DDFS) 2. Event-free survival and 3. Overall survival 4. Health-related quality of life and toxicity analyses according to CTC 5. Outcome in relation to tumour biological factors and polymorphism patterns 1. RFS in relation to the Sorlie classes using immunohistochemical markers and/or gene expression profiling comparing A vs B arm 2. RFS with receptor positive disease (analyzed in the local laboratories as described in the CRFs and also analyzed as continuous variables) in the comparison between the A- and B- arms. 3. RFS with high and low proliferation, respectively, (analyzed in the local laboratories as described in the CRFs and also analyzed as a continuous variable, or centrally analyzed), in the comparison between the A- and B-arms. 4. RFS in relation to HER-2/neu status (analyzed in the local laboratories as described in the CRFs) in the primary cancers in the comparison between the A- and B-arms and analyzed whether trastuzumab was given in sequence or concurrently. 5. RFS analyzed in relation to other molecular markers (e.g. gene expression profiling/ sequencing) in the primary cancers and SNPs signatures in normal DNA (related to toxicities for EC/FEC and docetaxel components, respectively, and given dose levels and outcome in relation to these factors and in relation QoL) to outcome per arm. 6. RFS analyzed in relation to tumour associated lymphocytes and Y-box binding protein in the comparison between the A- and B-arms. Tumour tissue will be obtained and stored for studies of prognostication and therapy prediction. Last patient randomized was September 2011.
Are described under the heading "Outcome measures"
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
2,017
Individually tailored and two weekly dosed epirubicin (start dose 90mg/m2) + cyclophosphamide (start dose 600mg/m2) followed by a three weeks break followed by biweekly and tailored docetaxel (start dose 75mg/m2) given every second week. If toxicity measured by CTC-NCI criteria are grade 2 or less (except haematological toxicity) it will be possible to escalate doses
Fixed dosed and three weekly epirubicin (100mg/m2), cyclophosphamide (500mg/m2) and 5-fluorouracil (500mg/m2), followed by fixed dosed and three weekly docetaxel (100mg/m2), no dose escalations.
MUG - Med. Univ.-Klinik Graz
Graz, Austria
MUI - Univ. Klinik f. Frauenheilkunde, Innsbruck
Innsbruck, Austria
LKH Leoben
Leoben, Austria
AKH Linz
Linz, Austria
KH BHS Linz
Linz, Austria
LKH Rankweil
Rankweil, Austria
Breast cancer relapse-free survival
Breast cancer recurrence free survival is defined as time from randomization to the first of the events; local-, regional- or distant breast cancer recurrence or death due to breast cancer or last date of follow-up if no event has occurred. This was defined already in the phase 2 protocol (1 Sept 2004).
Time frame: 2 years
Distant disease-free survival
Distant disease free survival is defined as time from randomization to the first of distant metastases or death due to breast cancer.
Time frame: 2 years
Event-free survival
Event-free survival is defined as time from randomization to the first of the events breast cancer recurrence (any type), contra-lateral breast cancer, other malignancy or any cause of death.
Time frame: 2 years
Overall survival
Overall survival is defined as time from randomization to any death.
Time frame: 2 years
Health-related quality of life and toxicity analyses according to CTC
Time frame: 2 years
Outcome in relation to tumour biological factors and polymorphism patterns
Comparing arm A vs B regarding: 1. RFS in relation to the Sorlie classes using immunohistochemical markers and/or gene expression profiling comparing A vs B arm; 2. RFS with receptor positive disease in the comparison between the A- and B arms; 3. RFS with high and low proliferation, respectively, in the comparison between the A- and B-arms.; 4. RFS in relation to HER-2/neu status in the primary cancers in the comparison between the A- and B-arms and analyzed whether trastuzumab was given in sequence or concurrently; 5. RFS analyzed in relation to other molecular markers in the primary cancers and SNPs signatures in normal DNA to outcome per arm; 6. RFS analyzed in relation to tumour associated lymphocytes and Y-box binding protein in the comparison between the A- and B-arms. Description of a to e are more detailed in the protocol, shortened here due to space limitation.
Time frame: 2 years
BCRFS in arm A in relation to given dose levels
Breast cancer relapse free survival
Time frame: 2 years
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KH BHB St. Veit/Glan
Saint Veit/Glan, Austria
LKH Salzburg / PMU
Salzburg, Austria
Brustzentrum Hanusch-KH
Vienna, Austria
Klinikum Wels - Grieskirchen GmbH
Wels, Austria
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