A Multicenter, Prospective Clinical Study of Neoadjuvant Therapy With Trastuzumab Plus Pertuzumab Combined With Metronomic Vinorelbine Chemotherapy in Elderly Patients With Early-Stage HER2-Positive Breast Cancer
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 45
- 主要终点
- Total pathological complete response (tpCR)
研究概览
简要总结
English Translation (Professional Medical Version) This study is a multicenter, prospective clinical trial designed to investigate the efficacy and safety of neoadjuvant therapy with trastuzumab plus pertuzumab combined with metronomic vinorelbine chemotherapy in elderly patients with HER2-positive breast cancer.
Eligible patients were aged ≥70 years, with histopathologically confirmed primary HER2-positive breast cancer, and met the indications for neoadjuvant therapy as stipulated in the clinical guidelines for the diagnosis and treatment of breast cancer.
A Simon two-stage design was employed in this study, with a planned total enrollment of 45 patients. In the first stage, 14 patients would be enrolled. If the number of observed responders was no more than 6, the trial would be terminated; otherwise, the trial would advance to the second stage, and the total sample size would be expanded to 45 patients.
The treatment regimen comprised 6 cycles of trastuzumab combined with pertuzumab (subcutaneous pertuzumab/trastuzumab fixed-dose combination was permitted as an alternative to intravenous formulations) plus metronomic vinorelbine therapy. Tumor response was assessed by imaging every 2 cycles. Patients with a confirmed response would complete all 6 cycles of treatment and undergo surgery per investigator assessment; postoperative pathological reports would be evaluated to determine the achievement of tpCR. For non-responders, the treatment regimen would be modified or surgery would be performed at the investigator's discretion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 70 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects voluntarily participate in this study and sign informed consent.
- •Age ≥70 years at the time of informed consent signing.
- •ECOG performance status (PS) 0-1; expected survival >3 months.
- •Primary HER2-positive breast cancer confirmed by histopathology or cytology.
- •Primary tumor diameter >2 cm, or axillary lymph node metastasis.
- •Laboratory indicators conform to the following standards:
- •Absolute neutrophil count (ANC) ≥1.5×10⁹/L; Absolute lymphocyte count (LC) ≥0.5×10⁹/L; Platelet count (PLT) ≥100×10⁹/L; Hemoglobin (Hb) ≥90 g/L; White blood cell count (WBC) 3.0×10⁹/L ≤ WBC ≤15×10⁹/L. Serum biochemistry (no blood transfusion or albumin infusion within 7 days before screening): ALT and AST ≤2.5×ULN; ALT and AST ≤5×ULN in patients with hepatic metastases. ALP ≤2.5×ULN (≤5×ULN for patients with bone tumor metastasis). BUN and Cr ≤1.5×ULN, and creatinine clearance ≥60 mL/min (Cockcroft-Gault formula).
- •PT and APTT ≤1.5×ULN, INR ≤1.5×ULN (patients not receiving anticoagulation therapy).
- •Urine protein <2+. If urine protein ≥2+, 24-hour urinary protein quantification ≤1 g.
- •Thyroid-stimulating hormone (TSH) ≤ULN. Left ventricular ejection fraction (LVEF) ≥50%. Patients with abnormal TSH may be enrolled as long as T3 and T4 levels are normal.
排除标准
- •Stage Ⅳ metastatic breast cancer, or patients who cannot undergo curative surgical resection after neoadjuvant therapy as assessed by investigators.
- •Prior anti-tumor therapies including chemotherapy, endocrine therapy, anti-HER2 biological therapy, or previous breast surgery (excluding diagnostic biopsy for primary breast cancer).
- •Other malignancies diagnosed within 3 years or concurrent malignant tumors at enrollment.
- •The following cases are eligible: Other malignancies treated solely by surgery with continuous 5-year disease-free survival (DFS); cured cervical carcinoma in situ, non-melanoma skin cancer, superficial bladder tumors (Ta: non-invasive tumor, Tis: carcinoma in situ, T1: basement membrane-invasive tumor).
- •Major surgery, incisional biopsy or severe traumatic injury within 28 days before study treatment (excluding diagnostic biopsy of primary breast cancer).
- •Persistent unhealed wounds or fractures.
- •History of uncontrolled psychoactive drug abuse or psychiatric disorders.
- •Severe and/or uncontrolled underlying systemic diseases, including:
- •History of hypertensive crisis or hypertensive encephalopathy; uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg after antihypertensive treatment).
- •Confirmed heart failure or cardiac systolic dysfunction (LVEF <55%).
- •Grade ≥2 myocardial ischemia, myocardial infarction, arrhythmia (QTc ≥450 ms for males, QTc ≥470 ms for females), or grade ≥2 congestive heart failure (NYHA classification).
- •Angina pectoris requiring anti-anginal medication.
- •Comorbidities interfering with scheduled treatment, including severe pulmonary dysfunction, active pulmonary disease, or uncontrolled severe infection (≥Grade 2 per CTCAE 5.0).
- •Allergy to any investigational drug, active ingredients or pharmaceutical excipients.
- •Subjects with comorbidities that threaten safety or affect study completion, or those unsuitable for enrollment according to investigator judgment.
研究组 & 干预措施
NHP
Vinorelbine soft capsules 40 mg, orally (PO), three times weekly (tiw) Trastuzumab: initial loading dose 8 mg/kg, maintenance dose 6 mg/kg, intravenous infusion, administered once every 3 weeks.
Pertuzumab: initial loading dose 840 mg, maintenance dose 420 mg, intravenous infusion, administered once every 3 weeks.
Each treatment cycle lasts 3 weeks. Imaging evaluations, including breast MRI, ultrasonography and computed tomography (CT), were performed every 2 cycles. For patients with tumor response, surgical indication was assessed after 6 cycles of treatment. Postoperative pathology was used to determine the pathological complete response (pCR) rate, and adjuvant treatment regimens were formulated according to postoperative pathological findings.
干预措施: neoadjuvant therapy (Combination Product)
结局指标
主要结局
Total pathological complete response (tpCR)
时间窗: through study completion, an average of 1 year
It indicates that no residual invasive cancer cells are detected pathologically in both primary breast lesions and axillary lymph nodes after neoadjuvant therapy and surgical operation.
次要结局
- Distant metastasis-free survival （DMFS）(5 years)
- Event-free survival （EFS）(5 years)
- Objective response rate in patients undergoing neoadjuvant therapy （ORR）(through study completion, an average of 1 year)
- Disease control rate（DCR）(through study completion, an average of 1 year)
- Invasive disease-free survival （iDFS）(5 years)
- Relapse-free survival （RFS）(5 years)
- Overall survival （OS）(7 years)
- Safety evaluation （SE）(through study completion, an average of 1 year)