Disitamab Vedotin in Combination With Pyrotinib Versus THP in the First-line Treatment for HER2-positive Advanced Breast Cancer, a Multicentre, Randomized, Double-blind Controlled, Phase III Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 312
- 试验地点
- 1
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
The goal of this multicentre, randomized, double-blind controlled, phase III clinical trial is to compare the efficacy and safety of disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of paclitaxel in combination with trastuzumab and pertuzumab (THP) for newly diagnosed recurrent/metastatic Human epidermal growth factor receptor 2 (HER2) positive advanced breast cancer, and to explore the impact of biomarkers on clinical efficacy and safety. The main questions it aims to answer are:
- Analyse the efficacy and safety of disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of THP.
- Explore the impact of biomarkers on clinical efficacy and safety of the combination of disitamab vedotin in combination with pyrotinib treatment.
Participants in the experimental group will receive disitamab vedotin in combination with pyrotinib for 6-8 cycles (each cycle lasting 28 days), followed by maintenance treatment with trastuzumab in combination with pyrotinib. Participants in the control group will receive paclitaxel in combination with trastuzumab and pertuzumab for 6-8 cycles (each cycle lasting 21 days), followed by maintenance treatment with trastuzumab and pertuzumab.
Researchers will compare disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of paclitaxel in combination with trastuzumab and pertuzumab to see if disitamab vedotin in combination with pyrotinib could be a new option for first-line treatment of HER2-positive metastatic breast cancer.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Adult female patients (age 18-75 years) with metastatic breast cancer confirmed by pathology or imaging;
- •Pathologically confirmed HER2 positive (definition: Immunohistochemistry(IHC) 3+, or IHC 2+ and Fluorescent In Situ Hybridization(FISH) amplification);
- •No previous chemotherapy regimen for metastatic breast cancer;
- •At least one measurable lesion exists (Response Evaluation Criteria in Solid Tumors(RECIST) 1.1);
- •Eastern Cooperative Oncology Group(ECOG) performance status score ≤ 2 and expected survival of not less than 3 months;
- •Prior treatment-related toxicity at enrollment must have resolved to National Cancer Institute(NCI) Common Terminology Criteria for Adverse Events(CTCAE) (version 5.0) ≤ 1 degree (except for alopecia or other toxicity that, in the judgment of the investigator, is not considered a risk to the safety of the patient);
- •Patients with adequate organ function before enrollment:
- •White Blood Cell (WBC) ≥ 3.0 x 10^9/L;
- •Neutrophil granulocyte (ANC) ≥1.5 x 10^9/L;
- •Platelet (PLT) ≥70×10^9/L;
- •Liver, kidney, and cardiac function tests are essentially normal (based on the normal values in the laboratory of each study center):
- •Total bilirubin (TBIL) ≤ 3 x Upper Limit of Normal (ULN);
- •Alanine aminotransferase (ALT/AST) ≤ 2.5 x ULN (≤ 5 x ULN in patients with liver metastases);
- •serum creatinine ≤ 1.5 x ULN or creatinine clearance (Ccr) ≥ 60 ml/min;
- •. Normal cardiac function;
- •Left ventricular ejection fraction (LVEF) ≥ 55%;
- •QT-interval corrected with Fridericia (QTcF) ≤ 470ms;
- •Hormone receptor status is clear;
- •Female patients of childbearing potential who have a negative pregnancy test and agree to use an effective non-hormonal method of contraception during treatment and for at least 6 months after the last dose of the test drug;
- •Able to understand the study process, voluntarily participate in this study, and sign an informed consent form.
排除标准
- •Pathology suggestive of HER2 negativity (IHC 2+ and FISH-, or IHC 1+);
- •Patients with known hypersensitivity to the active ingredient or other components of the study drug;
- •Patients during pregnancy or lactation, patients with childbearing potential tested positive in a baseline pregnancy test, or patients unwilling to take effective contraceptive measures throughout the trial;
- •Patients not eligible for this study judged by the investigator, a pre-existing disease or condition that may interfere with participation in the study or any serious medical disorder that may interfere with the safety of the subject (e.g., uncontrolled heart disease, high blood pressure, active or uncontrolled infections, active hepatitis B virus infection).
研究组 & 干预措施
disitamab vedotin in combination with pyrotinib
disitamab vedotin 2mg/kg IV every 14 days + Pyrotinib 400mg PO daily, with each 28-day cycle. After 6-8 cycles, adding Trastuzumab initially at 8mg/kg IV followed by 6mg/kg IV every 21 days + Pyrotinib 400mg PO daily for maintenance.
干预措施: disitamab vedotin (Drug)
disitamab vedotin in combination with pyrotinib
disitamab vedotin 2mg/kg IV every 14 days + Pyrotinib 400mg PO daily, with each 28-day cycle. After 6-8 cycles, adding Trastuzumab initially at 8mg/kg IV followed by 6mg/kg IV every 21 days + Pyrotinib 400mg PO daily for maintenance.
干预措施: Pyrotinib (Drug)
disitamab vedotin in combination with pyrotinib
disitamab vedotin 2mg/kg IV every 14 days + Pyrotinib 400mg PO daily, with each 28-day cycle. After 6-8 cycles, adding Trastuzumab initially at 8mg/kg IV followed by 6mg/kg IV every 21 days + Pyrotinib 400mg PO daily for maintenance.
干预措施: trastuzumab (Drug)
taxane drug in combination with trastuzumab and pertuzumab
taxane drug (Docetaxel/Paclitaxel/Albumin Paclitaxel/Liposomal Paclitaxel, dosing and administration per latest National Comprehensive Cancer Network(NCCN) and Chinese Society of Clinical Oncology(CSCO) breast cancer guidelines) + Trastuzumab initially at 8mg/kg IV followed by 6mg/kg IV every 21 days + Pertuzumab initially at 840mg IV followed by 420mg IV every 21 days, with each 21-day cycle. After 6-8 cycles, continuing with Trastuzumab at 6mg/kg IV every 21 days + Pertuzumab at 420mg IV every 21 days for maintenance.
干预措施: trastuzumab (Drug)
taxane drug in combination with trastuzumab and pertuzumab
taxane drug (Docetaxel/Paclitaxel/Albumin Paclitaxel/Liposomal Paclitaxel, dosing and administration per latest National Comprehensive Cancer Network(NCCN) and Chinese Society of Clinical Oncology(CSCO) breast cancer guidelines) + Trastuzumab initially at 8mg/kg IV followed by 6mg/kg IV every 21 days + Pertuzumab initially at 840mg IV followed by 420mg IV every 21 days, with each 21-day cycle. After 6-8 cycles, continuing with Trastuzumab at 6mg/kg IV every 21 days + Pertuzumab at 420mg IV every 21 days for maintenance.
干预措施: Pertuzumab (Drug)
taxane drug in combination with trastuzumab and pertuzumab
taxane drug (Docetaxel/Paclitaxel/Albumin Paclitaxel/Liposomal Paclitaxel, dosing and administration per latest National Comprehensive Cancer Network(NCCN) and Chinese Society of Clinical Oncology(CSCO) breast cancer guidelines) + Trastuzumab initially at 8mg/kg IV followed by 6mg/kg IV every 21 days + Pertuzumab initially at 840mg IV followed by 420mg IV every 21 days, with each 21-day cycle. After 6-8 cycles, continuing with Trastuzumab at 6mg/kg IV every 21 days + Pertuzumab at 420mg IV every 21 days for maintenance.
干预措施: taxane drug (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Estimated 30 months
From enrollment to progression or death (for any reason)
次要结局
- Disease control rate (DCR)(Estimated 30 months)
- Adverse Events (Based on CTCAE 5.0 standards)(From informed consent through 28 days following treatment completion)
- Quality of Life (QoL) by Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B)(Estimated 30 months)
- Overall Survival (OS)(Estimated 8 years)
- Clinical Benefit rate (CBR)(Estimated 30 months)
- Objective Response Rate (ORR)(Estimated 30 months)
- Exploration of biomarkers(Estimated 30 months)