CDK4/6 Inhibitors Intensification for Chemotherapy Omission in Small Size High-risk ER-positive Breast Cancer（Cinnamon）
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 2,288
- 主要终点
- iDFS
研究概览
简要总结
This study is a Phase III non-inferiority trial targeting a specific subset of early breast cancer patients: those with HR-positive/HER2-negative, node-negative small tumors (typically ≤2cm) but who exhibit high-risk features for recurrence (such as high histological grade, high Ki-67 index, etc.). Currently, the standard adjuvant treatment for these patients often includes chemotherapy followed by endocrine therapy, despite their small tumor size, due to the high-risk biological characteristics. However, chemotherapy can bring significant toxicity and long-term side effects.
This trial explores whether a chemotherapy-sparing approach is feasible. It compares the efficacy and safety of using the CDK4/6 inhibitor Dalpiciclib combined with endocrine therapy (AI ± OFS) directly, without chemotherapy, against the traditional approach of chemotherapy (TC regimen) followed by endocrine therapy. The primary goal is to demonstrate that the chemotherapy-free regimen is not inferior to the chemotherapy-containing regimen in terms of 5-year invasive disease-free survival (iDFS). If successful, this study could potentially de-escalate treatment for this high-risk population, sparing them from chemotherapy-related toxicities while maintaining excellent oncological outcomes.
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 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female, aged 18 to 70 years.
- •Histologically confirmed early breast cancer with pathological stage T1N0, 0.5 cm < tumor size ≤ 2 cm, ER-positive/HER2-negative, with ER expression ≥ 50%; and willingness to receive adjuvant dalpiciclib treatment.
- •Presence of at least one of the following high-risk features:
- •Ki-67 index ≥ 50%; Grade 3 (G3) tumor; an indication for chemotherapy based on results from multigene assays, including the 21-gene recurrence score and the 70-gene signature ; Age ≤ 40 years.
- •ECOG performance status: 0 to
- •Adequate organ function, defined as meeting the following criteria:
- •Hematology (no blood transfusion within 14 days): Hemoglobin (HB) ≥ 90 g/L; Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L; Platelet (PLT) ≥ 100 × 10⁹/L.
- •Biochemistry: Total Bilirubin (TBIL) ≤ 1.5 × Upper Limit of Normal (ULN); Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3 × ULN; Serum Creatinine (Cr) ≤ 1 × ULN, with creatinine clearance > 50 mL/min (calculated using the Cockcroft-Gault formula).
- •Voluntary participation with written informed consent, good compliance, and willingness to comply with follow-up requirements.
排除标准
- •Patients who have received neoadjuvant therapy, including chemotherapy, targeted therapy, radiotherapy, or endocrine therapy.
- •Bilateral breast cancer.
- •History of other prior malignancies, except for curatively treated basal cell carcinoma of the skin and carcinoma in situ of the cervix.
- •4) Evidence of metastasis at any site. 5) Any T4 lesion (UICC 1987), including skin involvement, tumor fixation/mass, or inflammatory breast cancer.
- •6) Pregnant or lactating women, or women of childbearing potential who are unwilling to use adequate contraception.
- •7) Concurrent participation in another clinical trial. 8) Severe organ dysfunction (cardiac, pulmonary, hepatic, or renal). Left Ventricular Ejection Fraction (LVEF) < 50% (by echocardiography). History of severe cardiovascular or cerebrovascular disease within 6 months prior to randomization (e.g., unstable angina, chronic heart failure, uncontrolled hypertension >150/90 mmHg, myocardial infarction, or cerebrovascular accident). Patients with poorly controlled diabetes mellitus or severe hypertension.
- •9) Known hypersensitivity to taxanes or their excipients. 10)Severe or uncontrolled infection. 11)History of psychoactive substance abuse that cannot be discontinued, or history of mental disorders.
- •Patients deemed by the investigator to be unsuitable for participation in this study.
- •Patient refusal to receive adjuvant dalpiciclib treatment.
研究组 & 干预措施
Chemotherapy-free arm
干预措施: Dalpiciclib+AI ± OFS (Drug)
standard-of-care
干预措施: TC (Docetaxel + Cyclophosphamide) × 4 cycles- endocrine therapy (Drug)
结局指标
主要结局
iDFS
时间窗: 5 years
It is defined as the percentage of patients who remain free of invasive disease recurrence, secondary primary invasive cancers, or death from any cause over a 5-year period from randomization or initiation of study treatment.
次要结局
- DFS(5 years)
- DDFS(5 years)
- RFS(5 years)
- OS(5 years)
- Safety and Tolerability(5 years)
- Quality of Life score in the per-protocol population(5 years)
研究者
Zhimin Shao
Director of the Department of Breast Surgery, Fudan University Shanghai Cancer Center
Fudan University