Randomized Phase III Trial for Evaluating the Efficacy of Adjuvant Abemaciclib in Patients With Locoregional Recurrence of Hormone Receptor-positive, HER2-negative Breast Cancer. JCOG2313, AURA Trial.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 290
- 试验地点
- 1
- 主要终点
- Invasive disease-free survival
研究概览
简要总结
The JCOG2313 trial is a multicenter, randomized, phase III study designed to evaluate the efficacy and safety of adjuvant abemaciclib in combination with endocrine therapy versus endocrine therapy alone in patients with hormone receptor (HR)-positive, HER2-negative breast cancer who have undergone curative treatment for their first locoregional recurrence (LRR).
Although HR-positive, HER2-negative breast cancer generally has a favorable prognosis, LRR-such as ipsilateral breast tumor recurrence (IBTR), chest wall recurrence, or regional lymph node recurrence-remains a clinically significant event that increases the risk of distant metastasis. While endocrine therapy is standard in this setting, the benefit of adding chemotherapy or other agents remains unclear, and treatment strategies vary widely.
Abemaciclib, a CDK4/6 inhibitor, has shown survival benefit in the adjuvant setting for high-risk early breast cancer. However, its role in post-LRR adjuvant treatment has not been evaluated in a randomized setting. This study aims to determine whether the addition of abemaciclib to endocrine therapy can improve invasive disease-free survival (IDFS) in patients after LRR.
Eligible patients are randomized 1:1 to receive either endocrine therapy alone or endocrine therapy plus abemaciclib (150 mg twice daily for 2 years). The primary endpoint is IDFS. Secondary endpoints include distant recurrence-free survival, breast cancer-specific survival, overall survival, and safety. A total of 290 patients will be enrolled. Randomization is stratified by site of recurrence, endocrine resistance, perioperative chemotherapy, and institution.
Additionally, a prospective ancillary study will assess circulating tumor DNA (ctDNA) as a biomarker for molecular residual disease (MRD). Plasma samples will be collected at predefined time points to evaluate the prognostic and predictive value of ctDNA for relapse and treatment response.
The JCOG2313 trial addresses an unmet need in the management of HR-positive, HER2-negative LRR and may contribute to the establishment of a new standard systemic therapy and personalized monitoring strategies.
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
- 未提供
排除标准
- •Presence of active double cancer (synchronous malignancy requiring treatment).
- •Ongoing infectious disease requiring systemic therapy.
- •Fever ≥38.0°C at the time of registration.
- •Women who are pregnant, possibly pregnant, within 28 days postpartum, or breastfeeding; men whose partners intend to become pregnant.
- •Psychiatric illness or symptoms that interfere with daily living and may compromise trial participation.
- •Ongoing systemic administration (oral or IV) of steroids equivalent to ≥10 mg/day of prednisolone or other immunosuppressive agents.
- •Unstable angina (developed or worsened within the past 3 weeks) or myocardial infarction within the past 6 months.
- •Uncontrolled hypertension.
- •Uncontrolled diabetes mellitus despite continuous insulin or oral antidiabetic therapy.
- •Positive for HBs antigen or HCV antibodies (Patients positive for HCV antibodies are not excluded if HCV-RNA is undetectable.)
- •Positive for HIV antibodies (HIV testing is not mandatory.)
- •Presence of interstitial pneumonia, pulmonary fibrosis, or severe emphysema as diagnosed by chest CT.
研究组 & 干预措施
Endocrine therapy in combination with abemaciclib (Arm B)
Participants in Arm B will receive endocrine therapy in combination with abemaciclib following curative-intent local treatment for first LRR of HR-positive, HER2-negative breast cancer.
干预措施: Endocrine therapy + Abemaciclib (Drug)
结局指标
主要结局
Invasive disease-free survival
时间窗: Up to 9 years (4 years of accrual and 5 years of follow-up)
Defined as the time from randomization to the first occurrence of one of the following events: * Recurrence of invasive breast cancer in the ipsilateral breast, chest wall, or regional lymph nodes (locoregional recurrence); * Distant recurrence of breast cancer (metastatic disease); * Invasive contralateral breast cancer; * Second primary invasive non-breast cancer (excluding non-melanoma skin cancer and in situ cervical cancer); * Death from any cause. Patients who have not experienced any of the above events will be censored at the date of last disease assessment.
次要结局
- Distant recurrence-free survival(Up to 9 years (4 years of accrual and 5 years of follow-up))
- Breast cancer-specific survival(Up to 9 years (4 years of accrual and 5 years of follow-up))
- Overall survival(Up to 9 years (4 years of accrual and 5 years of follow-up))
研究者
Yukinori Ozaki
Head Physician
Japanese Foundation for Cancer Research