Open-label, Randomized, Multicenter, International, Parallel Exploratory Phase II Study, Comparing 3 FEC-3 Docetaxel Chemotherapy to Letrozole + Palbociclib Combination as Neoadjuvant Treatment of Stage II-IIIA PAM 50 ROR-defined Low or Intermediate Risk Luminal Breast Cancer, in Postmenopausal Women
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- UNICANCER
- 入组人数
- 125
- 试验地点
- 2
- 主要终点
- Evaluation of the number of patients with a Residual Cancer Burden (RCB) 0-I index as a measure of efficacy
研究概览
简要总结
The investigators propose in the present study an innovative approach, combining the most recent therapeutic opportunities in high risk ER+ breast cancer with the most recent and innovative diagnostic approaches such as the PAM50 signature and the RCB tumor response evaluation method. In line with the most recent recommendations on targeted anticancer therapies, the investigators have designed a parallel phase II randomized trial with early stopping rules 26, which will able in the meantime to build a unique prospective collection of tumor tissue, pre- and post-treatment.
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
- •Aged ≥ 18 years, Post-menopausal women
- •Newly diagnosed and operable unilateral invasive breast cancer, not candidate or uncertain for breast conservation - Note: Multicentric/multifocal tumors are allowed provided a maximum of 3 lesions are present, and all share the same characteristics: ER Allred 4, Her2- (PAM50 will be performed in the largest lesion)
- •Stage II-IIIA
- •Assessment of nodal status available (Ultrasound guided FNA or biopsy if necessary)
- •Non metastatic, M0
- •ER-positive by IHC (Allred Score≥4)
- •HER2-negative by IHC (score 0 or 1+) and/or Fish/Cish
- •Either Luminal A AND proven nodal involvement (cytology or histology), or Luminal B through PAM50 ROR (Prosigna™) centralized evaluation
- •No prior systemic therapy for the present tumor
- •Adequate renal, hepatic, and hematopoietic functions as defined by the following criteria:
- •Absolute Neutrophil Count (ANC) ≥1,500/mm3 or ≥1.5 x 109/L
- •Platelets ≥100,000/mm3 or ≥100 x 109/L
- •Hemoglobin ≥9 g/dL
- •Serum Aspartate Transaminase (AST) and serum Alanine Aminotransferase Transaminase (ALT) ≤2.5 x upper limit of normal (ULN)
- •Alkaline phosphatase ≤2.5 x ULN
- •Total serum bilirubin ≤1 x ULN
- •Serum creatinine ≤1.5 x ULN or estimated creatinine clearance ≥ 60 mL/min as calculated using the method standard for the institution
- •Adequate cardiac functions, including:
- •12 Lead electrocardiogram (ECG) with normal tracing or non clinically significant changes that do not require medical intervention.
- •QTc interval ≤480 msec
- •No history of Torsades de Pointes or other symptomatic QTc abnormality.
- •Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures
- •Signed informed consent and health insurance coverage
排除标准
- •Non operable, bilateral, T4 or metastatic breast cancer
- •Limited T2 breast cancer immediately accessible to conservative surgery
- •Previous homolateral breast cancer (including in situ carcinoma), and/or contralateral breast cancer except if treated by surgery +/- radiation therapy alone without any systemic treatment
- •Previous hormone replacement therapy (HRT) stopped less than 2 weeks before beginning of treatment
- •Previous use of SERMs such as raloxifene
- •Any surgery (not including minor procedures such as lymph node biopsy, primary tumor core biopsy, fine needle aspiration) within 4 weeks of start of study treatment; or not fully recovered from any side effects of previous procedures.
- •Diagnosis of any previous malignancy within the last 5 years, except for adequately treated basal cell carcinoma, or squamous cell skin carcinoma, or in situ cervical carcinoma
- •History of any previous anti-cancer chemotherapy and any previous treatment using AI
- •Concurrent administration of herbal preparations as complementary medicine.
- •Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drugs, such as the inability to take oral medication in tablet form and malabsorption syndrome
- •Patient with any psychological, familial, social or geographical condition which could potentially hamper compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
研究组 & 干预措施
Chemotherapy
3 cycles of FEC 100 followed by 3 cycles of Docetaxel Drugs: Fluorouracile, Epirubicine, Cyclophosphamide, Docetaxel
干预措施: Fluorouracile (Drug)
Chemotherapy
3 cycles of FEC 100 followed by 3 cycles of Docetaxel Drugs: Fluorouracile, Epirubicine, Cyclophosphamide, Docetaxel
干预措施: Epirubicin (Drug)
Chemotherapy
3 cycles of FEC 100 followed by 3 cycles of Docetaxel Drugs: Fluorouracile, Epirubicine, Cyclophosphamide, Docetaxel
干预措施: Cyclophosphamide (Drug)
Letrozole Palbociclib
Drugs: letrozole + palbociclib combination
干预措施: Letrozole (Drug)
Letrozole Palbociclib
Drugs: letrozole + palbociclib combination
干预措施: Palbociclib (Drug)
结局指标
主要结局
Evaluation of the number of patients with a Residual Cancer Burden (RCB) 0-I index as a measure of efficacy
时间窗: 21 weeks
Residual cancer burden (RCB) is estimated from routine pathologic sections of the primary breast tumor site and the regional lymph nodes after the completion of neoadjuvant therapy. 6 variables are included in a calculation formula.
次要结局
- Evaluation of the clinical response in each treatment arm as defined by clinical and ultrasound examination.(21 weeks)
- Determination of the number and type of Adverse Events as a Measure of Safety and Tolerability(21 weeks)
- Correlation of the PAM50 risk of recurrence (ROR) score to its ability to predict RCB as defined in outcome 1(21 weeks)
- Calculation of the rates of breast conservation therapy in the two arms with regard to the initially planned surgery.(21 weeks)