Omission of Surgery and Sentinel Lymph Node Dissection in Clinically Low-risk HER2positive Breast Cancer With High HER2 Addiction and a Complete Response Following Standard Anti-HER2-based Neoadjuvant Therapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Disease-free Survival at 3years
研究概览
简要总结
This is a prospective, single arm, open-label, unicenter, exploratory study in women with primary operable HER2-positive, HER2-enriched/ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression), to evaluate the omission of surgery and sentinel lymph node dissection in patients with HER2-E and ERBB2 high breast cancer who achieving a complete response following standard anti-HER2-based neoadjuvant therapy with paclitaxel/trastuzumab/pertuzumab. The primary trial objective is to estimate the loco-regional invasive disease-free survival at 3-year of patients who achieve a complete response based on imaging (i.e. Magnetic resonance imaging) and a stereotactic-guided vacuum-assisted breast biopsy, and omit loco-regional surgery.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female participants who are at least 40 years of age on the day of signing the informed consent form with histologically confirmed diagnosis of breast cancer.
- •A participant is eligible to participate if she is not pregnant, not breastfeeding.
- •The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- •Histologically confirmed invasive adenocarcinoma of the breast, with all of the following characteristics:
- •HER2-positive status by local determination according to 2018 ASCO/CAP guidelines.
- •PAM50 HER2-enriched subtype and ERBB2-high as predefined cutoff as per central determination.
- •Unifocal invasive carcinoma: only 1 invasive focus can be observed (the tumor focus containing or not containing an in situ component)
- •Tumor largest diameter ≤4 cm as defined by breast MRI.
- •No nodal involvement (i.e. cN0). Any suspicious axillary node by ultrasound must be biopsied. If the biopsy or the FNA is negative of tumor cells, patient is eligible.
- •No evidence of distant metastasis (M0) by routine clinical assessment.
- •Patient must have known ER and PR status locally determined prior to study entry.
- •Eligible for taxane therapy.
- •Willingness of the patient to omit surgery if all criteria are met following neoadjuvant therapy.
- •Estimated life expectancy of at least 5 years irrespective of the diagnosis of breast cancer.
- •Breast cancer eligible for primary surgery
- •Have provided archival tumor tissue sample or newly obtained core. Formalin-fixed,paraffin embedded (FFPE) tissue blocks are mandatory. Available pre-treatment FFPE core biopsy evaluable for PAM50 or possibility to obtain one.
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Ability and willingness to comply with study visits, treatment, testing and to comply with the protocol.
- •Have adequate organ function.
排除标准
- •Has received prior anti-cancer therapy, including investigational agents, or treatment for primary invasive breast cancer.
- •Known hypersensitivity to any of the excipients of trastuzumab, pertuzumab, TDM1 or paclitaxel.
- •Clinical stage II, III or IV.
- •History of radiotherapy in the ipsilateral breast or axilla.
- •History of surgery of the ipsilateral axilla.
- •Bilateral invasive breast cancer.
- •Infiltrating lobular carcinoma.
- •Multicentric or multifocal breast cancer, defined as the presence of two or more foci of cancer in the same or different quadrants of the same breast.
- •Patients who have undergone sentinel lymph node biopsy prior to study treatment.
- •Patient has active cardiac disease or a history of cardiac dysfunction
- •Has an active infection requiring systemic therapy.
- •13. Patients with a history of previous breast cancer are excluded.
研究组 & 干预措施
Omission of surgery
Neoadjuvant period: paclitaxel IV 80mg/m2 every week for 12 weeks with trastuzumab and pertuzumab Subcutaneous Fixed-Dose Combination (FDC) (a loading dose of 1200 mg pertuzumab and 600 mg trastuzumab followed by a maintenance dose of 600 mg pertuzumab and 600 mg trastuzumab once every 3 weeks) for 5 cycles. Adjuvant period: If no invasive tumor cells and no in situ disease are identified in the stereotactic-guided VAB,patients will be eligible to omit loco-regional surgery. Whole breast radiotherapy without nodal radiotherapy will then be performed. Trastuzumab and pertuzumab FDC will be continued to complete 1 year of treatment and adjuvant endocrine therapy will be indicated according to hormonal receptor status by IHC.
干预措施: Trastuzumab and pertuzumab Subcutaneous Fixed-Dose Combination (Biological)
Surgery
Neoadjuvant period: paclitaxel IV 80mg/m2 every week for 12 weeks with trastuzumab and pertuzumab Subcutaneous Fixed-Dose Combination (FDC) (a loading dose of 1200 mg pertuzumab and 600 mg trastuzumab followed by a maintenance dose of 600 mg pertuzumab and 600 mg trastuzumab once every 3 weeks) for 5 cycles. Surgery: If invasive tumor cells and/or in situ disease are identified, patients will undergo surgery. Adjuvant period: All patients will continue with Trastuzumab-emtansine (T-DM1) completing 1 year of treatment (14 cycles) and adjuvant endocrine therapy will be indicated according to hormonal receptor status by IHC.
结局指标
主要结局
Disease-free Survival at 3years
时间窗: 3 years
To estimate the loco-regional invasive disease-free survival (LR-IDFS) at 3-year of patients who achieve a complete response based on imaging and a stereotactic-guided vacuum-assisted breast biopsy, and omit loco-regional surgery.
次要结局
- pCR Rate(pCR assessment was done following surgery after neoadjuvant therapy with paclitaxel and trastuzumzb/pertuzumab prior to adjuvant therapy)
- Patient Reported Outcomes (Global Health Status)(The questionnaire was filled by the patients at screening and post adjuvant therapy.)