A Prospective, Randomized, Open-label, Non-inferiority, Phase III Study Evaluating the Efficacy and Safety of 2 to 3 Years of Adjuvant Endocrine De-escalation Therapy for ER-positive/HER2-negative Stage I Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 2,934
- 试验地点
- 1
- 主要终点
- 5-year disease-free survival in the per-protocol population
研究概览
简要总结
This study is a prospective, randomized, open-label, non-inferiority Phase III clinical trial, planning to enroll 2,934 patients, with a 1:1 allocation to either the conventional endocrine therapy group or the de-escalation therapy group. The aim is to evaluate the safety and efficacy of 2-3 years of de-escalated endocrine therapy in patients with T1N0M0 potentially low-risk breast cancer, respectively.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Females aged 18 years or older;
- •Postoperative pathological stage I early breast cancer: histologically confirmed invasive carcinoma with a maximum diameter ≤2 cm and node-negative (N0);
- •Immunohistochemistry (IHC) shows ER-positive (ER ≥50%), HER2 IHC score of 0, 1+, or 2+ with no amplification confirmed by FISH, and Ki-67 ≤20%;
- •Presence of at least one of the following potential low-risk factors:
- •1）Tumor size ≤1 cm, 2）21-gene recurrence score <11, 3）Fudan digital pathological subtype classified as SNF1, 4）Age ≥65 years;
- •ECOG performance status of 0 or 1;
- •Patients with bilateral synchronous invasive lesions are eligible if both lesions are ER-positive, HER2-negative, and meet the tumor size criteria;
- •Normal major organ function, meeting the following criteria:
- •Hematological: HB ≥90 g/L (no transfusion within 14 days), ANC ≥1.5×10⁹/L, PLT ≥100×10⁹/L;
- •Biochemical: TBIL ≤1.5×ULN, ALT and AST ≤3×ULN, serum Cr ≤1×ULN, and creatinine clearance >50 mL/min (Cockcroft-Gault formula);
- •Participants voluntarily enroll, sign informed consent, demonstrate good compliance, and cooperate with follow-up.
排除标准
- •Primary tumor size >2 cm in maximum diameter and/or axillary lymph node positivity;
- •Prior neoadjuvant therapy, any systemic therapy, or local therapy (except surgery), including chemotherapy, targeted therapy, radiotherapy, or endocrine therapy;
- •Prior adjuvant chemotherapy;
- •Use of CDK4/6 inhibitors in the adjuvant setting;
- •History of other malignancies (except cured basal cell carcinoma or cervical carcinoma in situ);
- •Metastasis at any site;
- •Pregnancy, lactation, or women of childbearing potential unable to use effective contraception;
- •Concurrent participation in other clinical trials;
- •Severe cardiac, pulmonary, hepatic, or renal dysfunction; LVEF <50% (by echocardiography); severe cardio-cerebrovascular diseases within 6 months (e.g., unstable angina, chronic heart failure, uncontrolled hypertension >150/90 mmHg, myocardial infarction, or stroke); poorly controlled diabetes; severe hypertension;
- •Severe or uncontrolled infections;
- •History of drug abuse or psychiatric disorders;
- •Patients deemed unsuitable for the study by the investigator.
研究组 & 干预措施
5 years of standard endocrine therapy
The control group receives 5 years of standard endocrine therapy:
Premenopausal patients: Tamoxifen (10 mg, orally, twice daily, for 5 years) or Toremifene (60 mg, orally, once daily, for 5 years); Postmenopausal patients: Letrozole (2.5 mg, orally, once daily, for 5 years) or Anastrozole (1 mg, orally, once daily, for 5 years) or Exemestane (25 mg, orally, once daily, for 5 years); A sequential regimen of 2-3 years of Tamoxifen or Toremifene followed by 3-2 years of Letrozole, Anastrozole, or Exemestane is acceptable.
Ovarian function suppression is permitted for premenopausal patients. CDK4/6 inhibitors are not allowed during the treatment course
干预措施: Endocrine Therapy of Physician's Choice (Drug)
2-3 years of de-escalated endocrine therapy
The experimental group receives 2-3 years of endocrine therapy:
Premenopausal patients: Tamoxifen (10 mg, orally, twice daily, for 2-3 years) or Toremifene (60 mg, orally, once daily, for 2-3 years); Postmenopausal patients: Letrozole (2.5 mg, orally, once daily, for 2-3 years) or Anastrozole (1 mg, orally, once daily, for 2-3 years) or Exemestane (25 mg, orally, once daily, for 2-3 years).
Ovarian function suppression is permitted for premenopausal patients. CDK4/6 inhibitors are not allowed during the treatment course.
干预措施: Endocrine Therapy of Physician's Choice (Drug)
结局指标
主要结局
5-year disease-free survival in the per-protocol population
时间窗: 5 year
The proportion of patients in a clinical trial who remained free of disease recurrence, secondary primary cancers, and death from the disease for five years following treatment initiation, calculated specifically among those who completed the study intervention as predefined in the trial protocol(i.e., without major deviations such as incomplete treatment, use of prohibited therapies, or significant protocol violations).
次要结局
- Quality of Life score in the per-protocol population(5 year)
- safety(5 year)
- 5-year disease-free survival in the Full Analysis Set(5 year)
- 5-year invasive breast cancer-free survival in the per-protocol population(5 year)
- Overall survival in the per-protocol population(5 year)