Omission of Local Therapies in Women Patients With HER2-positive or Triple-negative Breast Cancer: A Two Arm, Phase 2, Non-inferiority Trial for Surveillance in Maximum Responders to Neoadjuvant Systemic Therapy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 152
- 试验地点
- 1
- 主要终点
- Events-free survival (EFS) for each study arm.
研究概览
简要总结
HER2-positive and Triple-negative are subtypes of breast cancer more sensitive to systemic therapies, where the complete pathological response rate may be higher than 50%. This gave rise to doubts about the usefulness of traditional local treatments for such responders. Omission of surgery after vacuum assisted breast biopsy (VABB) as well omission of radiotherapy after conservative surgery would now seem to be reasonable alternatives to standard care for highly selected patients, in whom systemic treatments have provided the maximum response.
详细描述
This is a prospective phase 2 non-randomized non-inferiority trial with two independent investigational arms. In each arm a 2-stage non-inferiority group-sequential design will be implemented; the overall sample per arm is of 76 patients, 43 of which will be recruited at the first stage. For each arm a futility evaluation is foreseen at the first stage, the results of which will be presented to an independent Data Safety and Monitoring Committee (iDSMC) (see "Statistical analyses" paragraph).
Arm A will evaluate the omission of surgery in unifocal T1-2 clinically N0, M0 patients who will demonstrate maximum response after neoadjuvant systemic treatment (i.e. whole breast irradiation only).
Arm B will evaluate the omission of radiotherapy in patients with complete pathological response proved by standard conservative surgical treatment (i.e. conservative surgery only). Patients candidate to arm A, who refuse the omission of surgery and then operated, are eligible for arm B if complete pathological response is confirmed after standard surgical treatment. Moreover, patients who refuse VABB and N1 patients with complete pathological response confirmed by partial mastectomy and surgical staging of axilla (SLNB and or TAD) are also eligible for arm B. Arm B patients must have confirmed complete pathological response by local-regional surgery. Therefore, omission of radiotherapy will be ultimately offered to a cohort of patients with T1-2, N0-1, M0 breast cancer conservatively operated, in whom complete pathological response to a neoadjuvant therapies is confirmed on the entire surgical specimen of the tumor bed and of the sampled nodes.
In each study arm non inferiority of 5-year EFS will be tested against historical data. No between arms statistical comparison is foreseen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 ≥ 18y.
- •Initial diagnosis of unifocal HER2-positive (regardless of HR status) or Triple-negative (HR positivity lower than 10% is allowed) T1-2, N0-1, M0 breast cancer.
- •Treated with neoadjuvant systemic treatment according to the center recommendations.
- •Maximum responders and/or complete pathological response proved by surgery.
- •Scheduled for breast conservation.
- •Giving specific informed consent.
排除标准
- •One of the inclusion criteria missed.
- •Residual ductal carcinoma in situ (DCIS) at VABB and/or surgery.
- •Bilateral synchronous breast cancer.
- •Previous malignancy within 5 years.
- •BRCA1-2, PALB2 or p53 proven mutation carrier (VUS are exclusion criteria as well).
- •Patients unable to perform regular follow up.
研究组 & 干预措施
A Omission of Surgery
Arm A will evaluate the omission of surgery in unifocal T1-2 clinically N0, M0 patients who will demonstrate maximum response after neoadjuvant systemic treatment (i.e. whole breast irradiation only).
干预措施: Omission of local therapies (Other)
B Omission of Radiotherapy
Arm B will evaluate the omission of radiotherapy in unifocal T1-2, N1, M0 patients with complete pathological response proved by standard conservative surgical treatment (i.e. conservative surgery only and surgical staging of axilla).
干预措施: Omission of local therapies (Other)
结局指标
主要结局
Events-free survival (EFS) for each study arm.
时间窗: 5 years
Events considered are: local recurrence, distant metastases, or death, whichever will occur first.
次要结局
- Time to rescue surgery(5 years)