Neoadjuvant Pyrotinib, Trastuzumab, Docetaxel Followed by Pertuzumab, Trastuzumab, Docetaxel Versus Pertuzumab, Trastuzumab, Docetaxel for the Treatment of Early or Locally Advanced HER2-Positive Breast Cancer: A Randomized, Multicenter, Open-Label Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 220
- 试验地点
- 1
- 主要终点
- tpCR
研究概览
简要总结
This is a randomized, open-label, superiority, multicenter clinical trial for patients with early or locally advanced (T≥2cm, N0-3, M0) HER2-positive breast cancer. It aims to compare the efficacy of neoadjuvant treatment with 2 cycles of Pyrotinib + Trastuzumab + Docetaxel followed by 2 cycles of Pertuzumab + Trastuzumab + Docetaxel versus 4 cycles of Pertuzumab + Trastuzumab + Docetaxel. Exploratory analyses of ctDNA clearance rate and MRI response will also be conducted.
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 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent.
- •Age: Female patients aged 18-70 years.
- •Breast cancer meeting the following criteria:
- •Histologically confirmed invasive breast cancer, with primary tumor diameter ≥ 2.0 cm, Stage II-III as assessed by local standard methods.
- •HER2-positive breast cancer, defined as Immunohistochemistry (IHC) score 3+ or In Situ Hybridization (ISH) showing HER2 gene amplification.
- •Eastern Cooperative Oncology Group (ECOG) performance status score ≤
- •All required baseline laboratory tests and imaging studies completed before randomization.
- •Adequate organ function
- •For non-menopausal (amenorrhea < 12 months) or non-surgically sterile female patients (without ovaries and/or uterus): Agreement to abstain or use reliable and effective contraception during treatment and for at least 6 months after the last dose of study treatment.
- •Investigator judgment that the patient can comply with the study protocol.
排除标准
- •Bilateral breast cancer or metastatic (Stage IV) breast cancer.
- •Significant cardiac disease:
- •History of myocardial infarction, acute coronary syndrome, or coronary angioplasty/stenting/bypass within the past 6 months.
- •New York Heart Association (NYHA) Class II-IV congestive heart failure (CHF) or history of NYHA Class III or IV CHF.
- •High-risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate > 100 bpm, significant ventricular arrhythmias (e.g., ventricular tachycardia), or higher-grade atrioventricular (AV) block.
- •Angina requiring anti-anginal medication.
- •Clinically significant valvular heart disease.
- •ECG evidence of transmural myocardial infarction.
- •Other malignancies within the past 5 years, except cured carcinoma in situ of the cervix or non-melanoma skin cancer.
- •Severe systemic infection or patients with other serious diseases.
- •Major non-breast surgery within 4 weeks of randomization, or patients who have not fully recovered from such surgery.
- •Known history of Human Immunodeficiency Virus (HIV) infection.
- •Active hepatitis B or hepatitis C virus infection.
- •Known allergy or intolerance to the study drugs or their excipients.
- •Prior cytotoxic chemotherapy, endocrine therapy, biological therapy, or radiotherapy for any reason.
- •Currently enrolled in or previously participated in a study of an investigational drug and received investigational treatment or used an investigational device within 4 weeks before the first dose of study treatment (12 months for investigational drugs/devices with anti-cancer or anti-proliferative properties).
- •Vaccination with a live vaccine within 30 days before the first dose of the investigational drug.
- •Psychiatric illness or substance abuse history that could affect compliance with trial requirements.
- •Pregnancy or breastfeeding, or female patients of childbearing potential who refuse to take appropriate contraceptive measures during the trial.
- •Patients judged by the investigator to be unsuitable for participation in this study.
研究组 & 干预措施
TPyP
2 cycles of Pyrotinib + Trastuzumab + Docetaxel followed by 2 cycles of Pertuzumab + Trastuzumab + Docetaxel
干预措施: Docetaxel (Drug)
TP
4 cycles of Pertuzumab + Trastuzumab + Docetaxel
干预措施: Docetaxel (Drug)
TP
4 cycles of Pertuzumab + Trastuzumab + Docetaxel
干预措施: Trastuzumab (Herceptin) (Drug)
TP
4 cycles of Pertuzumab + Trastuzumab + Docetaxel
干预措施: Pertuzumab (Drug)
TPyP
2 cycles of Pyrotinib + Trastuzumab + Docetaxel followed by 2 cycles of Pertuzumab + Trastuzumab + Docetaxel
干预措施: Trastuzumab (Herceptin) (Drug)
TPyP
2 cycles of Pyrotinib + Trastuzumab + Docetaxel followed by 2 cycles of Pertuzumab + Trastuzumab + Docetaxel
干预措施: Pyrotinib (Drug)
TPyP
2 cycles of Pyrotinib + Trastuzumab + Docetaxel followed by 2 cycles of Pertuzumab + Trastuzumab + Docetaxel
干预措施: Pertuzumab (Drug)
结局指标
主要结局
tpCR
时间窗: From enrollment to the end of treatment at 24 weeks
After completion of neoadjuvant therapy and surgery, no residual invasive carcinoma in the evaluation of hematoxylin and eosin stained of breast and lymph node samples
次要结局
- bpCR(From enrollment to the end of treatment at 24 weeks)
- EFS(through study completion, an average of 2 year)
- OS(through study completion, an average of 5 year)
- Early ctDNA clearance(From enrollment to the end of treatment at 24 weeks)
- Late ctDNA clearance(From enrollment to the end of treatment at 24 weeks)
- rCR(From enrollment to the end of treatment at 24 weeks)
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0(From enrollment to the end of treatment at 24 weeks)
研究者
Kunwei Shen
Professor
Shanghai Jiao Tong University School of Medicine