Comparison of Neoadjuvant Aromatase Inhibitors With Ovarian Suppression Versus Chemotherapy in Premenopausal Patients With Hormone Receptor-positive Breast Cancer (COMPETE): a Randomized Phase 3 Trial
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Overall response rate(ORR)
研究概览
简要总结
To compare the efficacy and safety of neoadjuvant aromatase inhibitor plus ovarian suppression with chemotherapy in premenopausal patients with hormone receptor-positive breast cancer.
详细描述
Neoadjuvant therapy is nowadays the standard treatment for both early stage and locally advanced breast cancer, and exhibited similar benefit compared with adjuvant therapy in terms of disease free and overall survival. Patients achieved pathological complete response(pCR) after neoadjuvant chemotherapy have superior outcome compared with those with residual tumors in breast and/or axilla. pCR is now the most wildly accepted surrogate marker for long-term survival of patients, especially in those with triple negative or human epidermal growth factor receptor-2(HER2)-positive breast cancer. However, in luminal HER2-negative breast cancer, neoadjuvant chemotherapy is not as effective as in other subtypes of breast cancer, pCR is less noted and seems barely correlated to long-term survival benefit.
In postmenopausal patients with hormone receptor-positive breast cancer, neoadjuvant endocrine therapy of aromatase inhibitor achieved similar clinical response rate compared with neoadjuvant chemotherapy, and in premenopausal hormone receptor-positive, HER2-negative breast cancer patients, neoadjuvant aromatase inhibitor plus ovarian function suppression(OFS) has showed more pronounced efficacy than tamoxifen plus OFS.
In adjuvant setting, aromatase inhibitor combined with OFS in premenopausal patients with hormone receptor-positive breast cancer has demonstrated superior benefit in terms of disease free survival, and has been established as one of the routine options of adjuvant endocrine therapy. Notwithstanding the remarkable performance of combination of aromatase inhibitor and OFS in adjuvant therapy, the role of this treatment strategy in neoadjuvant setting has yet not been proved when compared with neoadjuvant chemotherapy.
The aim of this study is to prospectively compare the efficacy and safety of neoadjuvant aromatase inhibitor plus OFS with chemotherapy in premenopausal patients with hormone receptor-positive HER2-negative breast cancer.
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Women aged ≥ 18 years
- •Histologically confirmed invasive breast cancer
- •American Joint Committee on Cancer (AJCC) stage: ⅡA-ⅢC, no evidence of metastasis
- •At least one measurable disease in breast and/or axilla
- •ER and/or progesterone receptor(PgR) positive(≥10% of the cells by IHC)
- •HER2 negative(by IHC and/or FISH)
- •Premenopause status (estradiol in premenopausal range or with normal menstrual cycle in the past 6 months with no use of hormonal drugs)
- •Eastern Cooperative Oncology Group（ECOG）score 0-1, an estimated life expectancy of at least 12 months
- •Adequate bone marrow function: Leukocyte ≥ 3.0*109/L; Neutrophil ≥ 1.5*109/L; Hb ≥ 100g/L; Platelet(PLT） ≥ 80*109/L
- •Adequate liver, renal function and coagulation function: Alanine transaminase（ALT） and/or Aspartate transaminase（AST）≤ 1.5 upper normal limit（UNL）, total bilirubin ≤upper normal limit, creatinine ≤ 110umol/L, Creatinine clearance > 60ml/min, blood urea nitrogen（BUN） ≤ 7.1mmol/L, activated partial thromboplastin time（APTT） ≤ 1.5 upper normal limit（UNL）
- •Women with child-bearing potential must have a negative pregnancy test (urine or serum) within 7 days of drug administration and agree to use an acceptable method of birth control to avoid pregnancy for the duration of the study
- •Serological records of hepatitis B virus（HBV）and hepatitis C virus（HCV） testing.
排除标准
- •Stage IV breast cancer
- •Prior systemic or loco-regional treatment of breast cancer
- •Any anti-neoplastic treatment within 28 days before the beginning of study
- •Known severe hypersensitivity to any drugs in this study
- •History of malignancy within 5 years except carcinoma in situ of cervix or skin basal cell carcinoma that had received adequate treatment
- •Peripheral neuropathy ≥ 2°, according to National Cancer Institute(NCI) Common Terminology Criteria for Adverse Events(CTCAE)(Version 4.0)
- •Any cardiac or pulmonary dysfunction defined as following:
- •(1) ≥ 3° symptomatic congestive heart failure (CHF) according to NCI CTCAE(Version 4.0) or ≥ 2° CHF according to New York Heart Association（NYHA）
- •(2) Angina that needs anti-anginal drugs, advanced conduction abnormality or significant vascular disease
- •(3) Uncontrolled high-risk arrhythmia: atrial tachycardia that silent heart rate >100/min, significant ventricular arrythmia or advanced atrioventricular block(2° type II atrioventricular or 3° atrioventricular block)
- •(4) Poorly controlled hypertension (systolic BP > 180 mmHg or diastolic BP > 100 mmHg)
- •(5) Transmural myocardial infarction in EKG
- •(6) Long-term oxygen therapy
- •Uncontrolled severe systemic disease(clinically significant cardiovascular disease，pulmonary disease or metabolic disease, wound healing disorder, ulcer, severe infection)
- •Pregnant or breast feeding
- •Major operation, obvious trauma within 28 days before randomization or planned major operation during the study
- •Known active hepatic disease due to hepatitis B virus, hepatitis C virus, auto-immune liver disease or sclerosing cholangitis
- •Known HIV infection
- •Any reasons investigators consider that not suitable for the study
研究组 & 干预措施
Neoadjuvant endocrine therapy
Six months of exemestane or anastrozole plus goserelin.
干预措施: Neoadjuvant endocrine therapy (Drug)
Neoadjuvant chemotherapy
Six cycles of docetaxel plus epirubicin and cyclophosphamide(TEC).
干预措施: Neoadjuvant chemotherapy (Drug)
结局指标
主要结局
Overall response rate(ORR)
时间窗: up to 7 months
Overall response rate(ORR) is defined as complete response rate plus partial response rate.
次要结局
- Pathological complete response(pCR)(up to 7 months)
- Incidence of grade 3-4 adverse events(participants will be followed during the six months of neoadjuvant therapy)
- Incidence of neutropenia fever(participants will be followed during the six months of neoadjuvant therapy)
- Incidence of hot flushes/flashes(participants will be followed during the six months of neoadjuvant therapy)
- Incidence of osteoporosis(participants will be followed during the six months of neoadjuvant therapy)
- Breast conserving surgery(BCS) rate(up to 7 months)