Prospective Non-Randomized Phase II Study of De-escalated Neoadjuvant Chemotherapy With Paclitaxel, Trastuzumab, and Pertuzumab (THP) Compared to Standard Regimen (TCHP) in Patients With Early HER2-Positive Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 186
- 试验地点
- 1
- 主要终点
- Pathological Complete Response (pCR) Rate
研究概览
简要总结
This phase II study evaluates the efficacy and safety of a de-escalated neoadjuvant chemotherapy regimen in patients with early-stage HER2-positive breast cancer. The experimental regimen consists of 12 weekly cycles of paclitaxel combined with trastuzumab and pertuzumab (THP), without anthracyclines.
The study aims to determine if this less toxic regimen can achieve high rates of pathological complete response (pCR) comparable to standard anthracycline-containing regimens. The results are compared with a historical control group of patients who received the standard TCHP regimen (docetaxel, carboplatin, trastuzumab, pertuzumab).
A total of 186 participants are included in the analysis: 93 patients prospectively treated with the de-escalated THP regimen and 93 patients in the retrospective historical control group (TCHP). The primary endpoint is the pCR rate at the time of surgery. Secondary endpoints include toxicity, rate of breast-conserving surgery, and 3-year event-free survival.
详细描述
Background:
Standard neoadjuvant therapy for HER2-positive breast cancer often includes anthracyclines (AC-THP) or platinum-based regimens (TCHP), which are associated with significant toxicity. De-escalation strategies aim to reduce toxicity without compromising efficacy, particularly in patients with early-stage disease.
Study Design:
This is an investigator-initiated, single-center, open-label, non-randomized phase II study.
- Prospective Cohort (n=93): Patients with Stage IIA-IIB (cT1-2 N0-1, cT3 N0) HER2+ breast cancer receive Paclitaxel (80 mg/m2 weekly for 12 weeks) + Trastuzumab (loading 8 mg/kg, then 6 mg/kg q3w) + Pertuzumab (loading 840 mg, then 420 mg q3w).
- Historical Control Cohort (n=93): Patients with similar baseline characteristics (Stage IIA-IIB) treated with standard TCHP regimen (Docetaxel 75 mg/m2 + Carboplatin AUC6 + Trastuzumab + Pertuzumab q3w for 6 cycles).
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 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed invasive breast carcinoma.
- •HER2-positive status defined as IHC 3+ or FISH amplification (ratio >= 2.0).
- •Clinical Stage IIA-IIB (cT1-T2 N0-N1, cT3 N0, M0).
- •Operable disease planned for surgical resection.
- •ECOG performance status 0-
- •Left Ventricular Ejection Fraction (LVEF) >= 50% by Echocardiography.
- •Adequate bone marrow, hepatic, and renal function.
- •Signed informed consent form.
排除标准
- •Metastatic disease (Stage IV).
- •Prior systemic therapy for breast cancer (chemotherapy, immunotherapy, or anti-HER2 therapy).
- •Serious cardiac history (congestive heart failure, unstable angina, myocardial infarction within 6 months).
- •Other synchronous or metachronous malignancies within 5 years (except non-melanoma skin cancer or carcinoma in situ of the cervix).
- •Pregnancy or breastfeeding.
- •Known hypersensitivity to study drugs.
研究组 & 干预措施
Experimental: De-escalated THP
Patients receive de-escalated neoadjuvant chemotherapy consisting of 12 weekly cycles of Paclitaxel combined with Trastuzumab and Pertuzumab (THP regimen), followed by surgery.
干预措施: Paclitaxel (Drug)
Experimental: De-escalated THP
Patients receive de-escalated neoadjuvant chemotherapy consisting of 12 weekly cycles of Paclitaxel combined with Trastuzumab and Pertuzumab (THP regimen), followed by surgery.
干预措施: trastuzumab (Drug)
Experimental: De-escalated THP
Patients receive de-escalated neoadjuvant chemotherapy consisting of 12 weekly cycles of Paclitaxel combined with Trastuzumab and Pertuzumab (THP regimen), followed by surgery.
干预措施: Pertuzumab (Drug)
Experimental: De-escalated THP
Patients receive de-escalated neoadjuvant chemotherapy consisting of 12 weekly cycles of Paclitaxel combined with Trastuzumab and Pertuzumab (THP regimen), followed by surgery.
干预措施: Radical Surgery (Procedure)
Experimental: De-escalated THP
Patients receive de-escalated neoadjuvant chemotherapy consisting of 12 weekly cycles of Paclitaxel combined with Trastuzumab and Pertuzumab (THP regimen), followed by surgery.
干预措施: Adjuvant Systemic Therapy (Drug)
Historical Control: Standard TCHP
Retrospective cohort of patients who received standard neoadjuvant chemotherapy with Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab (TCHP regimen) for 6 cycles.
干预措施: trastuzumab (Drug)
Historical Control: Standard TCHP
Retrospective cohort of patients who received standard neoadjuvant chemotherapy with Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab (TCHP regimen) for 6 cycles.
干预措施: Pertuzumab (Drug)
Historical Control: Standard TCHP
Retrospective cohort of patients who received standard neoadjuvant chemotherapy with Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab (TCHP regimen) for 6 cycles.
干预措施: Docetaxel (Drug)
Historical Control: Standard TCHP
Retrospective cohort of patients who received standard neoadjuvant chemotherapy with Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab (TCHP regimen) for 6 cycles.
干预措施: carboplatin (Drug)
Historical Control: Standard TCHP
Retrospective cohort of patients who received standard neoadjuvant chemotherapy with Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab (TCHP regimen) for 6 cycles.
干预措施: Radical Surgery (Procedure)
Historical Control: Standard TCHP
Retrospective cohort of patients who received standard neoadjuvant chemotherapy with Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab (TCHP regimen) for 6 cycles.
干预措施: Adjuvant Systemic Therapy (Drug)
结局指标
主要结局
Pathological Complete Response (pCR) Rate
时间窗: At the time of surgery (approximately 12-18 weeks after treatment initiation)
Defined as the absence of invasive cancer in the breast and axillary lymph nodes (ypT0/is ypN0) at the time of surgery
次要结局
- Incidence of Grade 3-4 Adverse Events(From first dose until 30 days after last dose)
- Rate of Breast-Conserving Surgery(At the time of surgery)
- 3-Year Event-Free Survival (EFS)(3 years from enrollment)