A Randomized Phase III Study of Response-Guided Therapy Following Neoadjuvant Endocrine Therapy to Optimize Adjuvant Treatment in Premenopausal HR+/HER2- Breast Cancer (JCOG2402, Young HOPE)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 950
- 试验地点
- 49
- 主要终点
- Event free survival
研究概览
简要总结
Young HOPE/JCOG2402 is a multicenter, randomized phase III study designed to evaluate response-guided therapy following neoadjuvant endocrine therapy to optimize adjuvant treatment in premenopausal HR+/HER2- Breast Cancer.
Premenopausal women with intermediate-risk HR-positive/HER2-negative breast cancer derive benefit from the addition of chemotherapy to endocrine therapy. However, previous studies have demonstrated that patients who achieve an endocrine response (Ki-67 ≤10%) following neoadjuvant endocrine therapy have excellent outcomes without chemotherapy, irrespective of menopausal status. These findings suggest that endocrine therapy response may serve as a predictive biomarker to identify premenopausal patients who can safely omit chemotherapy.
The primary objective of this study is to evaluate the non-inferiority of an ET response-guided treatment strategy compared with standard surgery followed by adjuvant therapy. The study aims to increase the proportion of patients who can be treated with endocrine therapy alone by omitting chemotherapy in those with highly endocrine-sensitive disease.
Eligible patients are randomized 1:1 to upfront surgery or neoadjuvant endocrine therapy with an aromatase inhibitor and ovarian function suppression. The primary endpoint is EFS. Secondary endpoints include overall survival, relapse-free survival, distant recurrrence-free survival, HR-QOL, the rate of endocrine therapy alone in adjuvant therapy, ET response rate in an Arm B, the rate of non-menopause and safety. A total of 950 patients will be enrolled. Randomization is stratified by cN0 vs cN1, HG1 or 2 vs 3, and institution.
The JCOG2402 trial addresses an unmet need in adjuvant therapy of premenopausal HR-positive, HER2-negative breast cancer with intermediate risk and may contribute to the establishment of a new treatment strategy.
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
- •Women aged 18 years or older
- •ECOG PS 0-1
- •HR-positive/HER2-negative breast cancer
- •ER expression ≥ 10%
- •cN0; HG 1: 3 cm<T≤5 cm, HG 2: 2 cm<T≤5 cm or HG3: 1 cm<T≤5 cm cN1; cT<5 cm and HG 1/HG 2
- •Premenopausal women with spontaneous menses within 12 months
- •No distant metastasis of breast cancer
- •No prior diagnosis of breast cancer.
- •No multiple regions of breast cancer
- •No contralateral breat cancer
- •Adequate organ function
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
Upfront surgery (Arm A)
Participants in Arm A will undergo breast surgery and adjuvant systemic treatment.
干预措施: Adjuvant systemic therapy based on pathological findings (Drug)
Neoadjuvant endocrine therapy (Arm B)
Participants in Arm B will receive neoadjuvant endocrine therapy of aromatase inhibitor and OFS for three months, followed by breast surgery.
干预措施: Adjuvant systemic therapy based on pathological findings and ET response (Drug)
结局指标
主要结局
Event free survival
时间窗: Up to 12 years (5 years of accrual and 7 years of follow-up)
Time from randomization to the first diagnosis of local invasive recurrence, regional recurrence, distant recurrence, contralateral invasive breast cancer, inoperable progressive disease during neoadjuvant endocrine therapy, second primary invasive non-breast cancer (excluding non-melanoma skin cancer and in situ cervical cancer), or death from any cause
次要结局
- Overall survival(Up to 12 years (5 years of accrual and 7 years of follow-up))
- Relapse-free survival(Up to 12 years (5 years of accrual and 7 years of follow-up))
- Distant recurrence-free survival(Up to 12 years (5 years of accrual and 7 years of follow-up))
研究者
Makiko Ono
Associate Professor
Tokyo Women's Medical University