A Randomised Phase 3 Study Comparing Biweekly and Tailored Epirubicin + Cyclophosphamide Followed by Biweekly Tailored Docetaxel Versus Three Weekly Epirubicin + Cyclophosphamide + 5-fluorouracil Followed by Docetaxel in Lymph Node Positive or High Risk Lymph Node Negative Breast Cancer Patients
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 2,017
- 试验地点
- 71
- 主要终点
- Breast cancer relapse-free survival
研究概览
简要总结
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
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Distant disease-free survival (DDFS)
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Event-free survival and
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Overall survival
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Health-related quality of life and toxicity analyses according to CTC
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Outcome in relation to tumour biological factors and polymorphism patterns
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RFS in relation to the Sorlie classes using immunohistochemical markers and/or gene expression profiling comparing A vs B arm
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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.
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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.
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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.
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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.
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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.
详细描述
Are described under the heading "Outcome measures"
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Histological proven invasive primary breast cancer, with at least 5 (recommended 10) removed axillary lymph nodes OR negative sentinel node biopsy performed for the node negative cohort. Interval between definitive surgery that includes axillary lymph node dissection and registration must be less than 60 days. Paraffin block from the primary tumour must be retained (not mandatory for Austrian sites). Frozen tumour tissue is strongly recommended to be stored.
- •Receptor negative or positive tumours with 1 or more positive axillary lymph nodes (more than 0.2 mm) OR axillary node negative breast cancers if the primary tumour is larger than 20 mm and receptor negative (Er and Pgr with no receptor content) and being Elston grade III. In Germany high risk node negative breast cancer patients are not eligible until labelling for docetaxel includes node-negative disease.
- •A primary breast cancer patient being 35 years or younger considered suitable for adjuvant chemotherapy (may be receptor negative or positive, HER-2/neu negative or positive, with or without axillary lymph node metastases).
- •Macroscopically and microscopically free margins after radical surgery (no cancer cells at borders of resection).
- •No proven distant metastases (negative chest/pulmonary X-ray, bone scintigram (when clinical signs of skeletal metastases or elevated ALP) supplemented with normal conventional X-ray of hot spots, normal liver function test and haematological function tests; when abnormal values, CT or ultrasound of the liver, patient can be included if no metastases are demonstrated.
- •Female age 18-
- •Ambulant patients (ECOG 1 or less).
- •No major cardiovascular morbidity NYHA I or II. (Appendix 3).
- •Written informed consent according to the local ethics committee requirements.
- •Patients of childbearing potential should have a negative pregnancy test within seven days of registration. (In Austria, pregnancy tests have to be repeated monthly during the treatment phase).
排除标准
- •Previous neo-adjuvant treatment.
- •Non-radical surgery (histopathological positive margins).
- •Proven distant metastases.
- •Pregnancy or lactation.
- •Other serious medical condition.
- •Previous or concurrent malignancies at other sites, except basal cell carcinoma and/or squamous cell carcinoma in situ of the skin or cervix. Patients with previous breast cancer (invasive and/or ductal carcinoma in situ) in the other breast without loco-regional (large lung volumes) radiotherapy, without objective findings for relapse, with > 5 years since diagnosis can be included.
- •Abnormal laboratory values precluding the possibility to safely deliver the used cytotoxic agents in the study.
- •Hypersensitivity to drugs formulated in polysorbate
- •Peripheral neuropathy grade ≥2.
研究组 & 干预措施
Arm A: dtEC→dtT
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
干预措施: dtEC→dtT (Drug)
Arm B: FEC→T
Fixed dosed and three weekly epirubicin, cyclophosphamide and 5-fluorouracil, followed by fixed dosed and three weekly docetaxel
干预措施: FEC→T (Drug)
结局指标
主要结局
Breast cancer relapse-free survival
时间窗: 2 years
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).
次要结局
- Distant disease-free survival(2 years)
- Event-free survival(2 years)
- Overall survival(2 years)
- Health-related quality of life and toxicity analyses according to CTC(2 years)
- Outcome in relation to tumour biological factors and polymorphism patterns(2 years)
- BCRFS in arm A in relation to given dose levels(2 years)
研究者
Prof Jonas Bergh
MD, PhD
Karolinska University Hospital