A Prospective, Double-Arm Study on the Optimization of Dynamic Neoadjuvant Therapy Strategies for HER2-Positive Breast Cancer Based on HER2-PET/CT Molecular Imaging
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 156
- 主要终点
- rate of pathologic complete response (pCR)
研究概览
简要总结
This study evaluates HER2-PET/CT-guided dynamic optimization of neoadjuvant therapy in patients with early-stage HER2-positive breast cancer. Based on metabolic response after two cycles, patients receive either intenstified treatment (Arm A) or de-escalation treatment (Arm B), alongside with a concurrent standard-treatment control group (Arm C). The study aims to establish a response-adaptive, imaging-guided treatment paradigm to optimize neoadjuvant therapy in HER2-positive breast cancer.
详细描述
This is a prospective, two-arm, interventional study. Eligible patients with early-stage HER2-positive breast cancer are enrolled into Arm A (TCbHP: trastuzumab, pertuzumab, docetaxel/nab-paclitaxel, and carboplatin) or Arm B (trastuzumab, pertuzumab, CDK4/6 inhibitor, and aromatase inhibitor), based on molecular subtype and patient preference. Patients in the control group (ArmC) will receive standard TCbHP therapy without intervention. All patients will undergo HER2-PET/CT imaging at baseline and after two cycles of treatment. Metabolic response, defined as a ≥40% reduction in SUVmax of target lesions, guides subsequent therapy: responders continue the initial regimen, while non-responders switch to an alternative strategy (ADC in Arm A or TCbHP in Arm B). The primary endpoint is the total pathological complete response (tpCR) rate in Arm A and ArmB.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary participation with written informed consent obtained prior to any study-related procedures
- •Age ≥ 18 years, male or female.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
- •Histologically confirmed HER2-positive (IHC 3+, or IHC 2+ with ISH amplification) stage I-III (cT1-3/cN0-2) breast cancer
- •Tumor diameter ≥ 1.5 cm assessed by imaging, with at least one PET-evaluable lesion present
- •Patient must have known estrogen receptor (ER) and progesterone receptor (PR) status. For Arm B, ER expression ≥ 10% and must be strongly positive.
- •Adequate bone marrow, liver, and renal function: WBC > 3.0 × 10⁹/L, ANC ≥ 1.5 × 10⁹/L, PLT ≥ 100 × 10⁹/L, Hb ≥ 10.0 g/dL; total bilirubin ≤ ULN (excluding Gilbert's syndrome), ALP ≤ 2.5 × ULN, AST/ALT ≤ 1.5 × ULN; creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min.
- •Patients who participate in the trial have good compliance and are willing to comply with the follow-up visit.
排除标准
- •Prior treatment with any chemotherapy, anti-HER2 therapy, radiotherapy, or endocrine therapy, etc
- •Locally advanced (cT4/cN3) or bilateral breast cancer
- •Patients with known allergies to any active ingredients or excipients of investigational medicinal product
- •Other malignancy diagnosed within 5 years prior to enrollment, excluding cervical carcinoma in situ and cured melanoma skin cancer
- •Left ventricular ejection fraction (LVEF) < 55%
- •Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg)
- •Severely cardiovascular disease
- •Current known infection with HIV, hepatitis B virus, or hepatitis C virus
- •Patients with pulmonary disease requiring continuous oxygen therapy, previous history of bleeding diathesis or patient is currently receiving anti-coagulant therapy, or immunosuppressive agent
- •Major surgical procedure or significant traumatic injury
- •Patient has other concurrent severe and/or uncontrolled medical conditions.
- •Concurrent participation in other interventional clinical trial
- •History of receiving any investigational treatment within 28 days prior to randomization
- •Pregnant or breast-feeding women or patients not willing to apply highly effective contraception as defined in the protocol
- •Inability to lie flat or presence of psychiatric disorders such as claustrophobia
研究组 & 干预措施
Cohort C
Patients who will receive surgery after completion of standard TCbHP regimen were be consecutively enrolled. Neither HER2-PET evaluation nor regimen adjustment based on the evaluation results was allowed.
干预措施: Docetaxel or Nab-paclitaxel (Drug)
Cohort A
The initial treatment regimen is the TCbHP (Trastuzumab + Pertuzumab + Docetaxel/Nab-paclitaxel + Carboplatin). After two cycles, patients assessed as metabolic responders by HER2 PET continue the TCbHP regimen for a total of six cycles, followed by surgery. Metabolic non-responders are switched to either SHR-A1811 (4.8 mg intravenously every 21 days) or Trastuzumab Deruxtecan (T-DXd, 5.4 mg/kg intravenously every 21 days) for four cycles of intensified therapy.
干预措施: Pertuzumab (Drug)
Cohort A
The initial treatment regimen is the TCbHP (Trastuzumab + Pertuzumab + Docetaxel/Nab-paclitaxel + Carboplatin). After two cycles, patients assessed as metabolic responders by HER2 PET continue the TCbHP regimen for a total of six cycles, followed by surgery. Metabolic non-responders are switched to either SHR-A1811 (4.8 mg intravenously every 21 days) or Trastuzumab Deruxtecan (T-DXd, 5.4 mg/kg intravenously every 21 days) for four cycles of intensified therapy.
干预措施: carboplatin (Drug)
Cohort A
The initial treatment regimen is the TCbHP (Trastuzumab + Pertuzumab + Docetaxel/Nab-paclitaxel + Carboplatin). After two cycles, patients assessed as metabolic responders by HER2 PET continue the TCbHP regimen for a total of six cycles, followed by surgery. Metabolic non-responders are switched to either SHR-A1811 (4.8 mg intravenously every 21 days) or Trastuzumab Deruxtecan (T-DXd, 5.4 mg/kg intravenously every 21 days) for four cycles of intensified therapy.
干预措施: Trastuzumab (Herceptin) (Drug)
Cohort A
The initial treatment regimen is the TCbHP (Trastuzumab + Pertuzumab + Docetaxel/Nab-paclitaxel + Carboplatin). After two cycles, patients assessed as metabolic responders by HER2 PET continue the TCbHP regimen for a total of six cycles, followed by surgery. Metabolic non-responders are switched to either SHR-A1811 (4.8 mg intravenously every 21 days) or Trastuzumab Deruxtecan (T-DXd, 5.4 mg/kg intravenously every 21 days) for four cycles of intensified therapy.
干预措施: Combination product: Trastuzumab + Pertuzumab (Drug)
Cohort B
The initial treatment regimen consists of trastuzumab + pertuzumab + CDK4/6 inhibitor + aromatase inhibitor (AI) ± GnRHa. After two cycles, patients assessed as metabolic responders by HER2 PET continue the original regimen for a total of six cycles of dual HER2-antibody (HP), followed by surgery. Non-responders are switched to the TCbHP regimen for another six cycles, followed by surgery.
干预措施: Combination product: Trastuzumab + Pertuzumab (Drug)
Cohort C
Patients who will receive surgery after completion of standard TCbHP regimen were be consecutively enrolled. Neither HER2-PET evaluation nor regimen adjustment based on the evaluation results was allowed.
干预措施: Combination product: Trastuzumab + Pertuzumab (Drug)
Cohort C
Patients who will receive surgery after completion of standard TCbHP regimen were be consecutively enrolled. Neither HER2-PET evaluation nor regimen adjustment based on the evaluation results was allowed.
干预措施: carboplatin (Drug)
Cohort A
The initial treatment regimen is the TCbHP (Trastuzumab + Pertuzumab + Docetaxel/Nab-paclitaxel + Carboplatin). After two cycles, patients assessed as metabolic responders by HER2 PET continue the TCbHP regimen for a total of six cycles, followed by surgery. Metabolic non-responders are switched to either SHR-A1811 (4.8 mg intravenously every 21 days) or Trastuzumab Deruxtecan (T-DXd, 5.4 mg/kg intravenously every 21 days) for four cycles of intensified therapy.
干预措施: Docetaxel or Nab-paclitaxel (Drug)
Cohort B
The initial treatment regimen consists of trastuzumab + pertuzumab + CDK4/6 inhibitor + aromatase inhibitor (AI) ± GnRHa. After two cycles, patients assessed as metabolic responders by HER2 PET continue the original regimen for a total of six cycles of dual HER2-antibody (HP), followed by surgery. Non-responders are switched to the TCbHP regimen for another six cycles, followed by surgery.
干预措施: Docetaxel or Nab-paclitaxel (Drug)
Cohort B
The initial treatment regimen consists of trastuzumab + pertuzumab + CDK4/6 inhibitor + aromatase inhibitor (AI) ± GnRHa. After two cycles, patients assessed as metabolic responders by HER2 PET continue the original regimen for a total of six cycles of dual HER2-antibody (HP), followed by surgery. Non-responders are switched to the TCbHP regimen for another six cycles, followed by surgery.
干预措施: CDK4/6 inhibitor (Drug)
Cohort B
The initial treatment regimen consists of trastuzumab + pertuzumab + CDK4/6 inhibitor + aromatase inhibitor (AI) ± GnRHa. After two cycles, patients assessed as metabolic responders by HER2 PET continue the original regimen for a total of six cycles of dual HER2-antibody (HP), followed by surgery. Non-responders are switched to the TCbHP regimen for another six cycles, followed by surgery.
干预措施: Aromatase Inhibitor (AI) (Drug)
Cohort C
Patients who will receive surgery after completion of standard TCbHP regimen were be consecutively enrolled. Neither HER2-PET evaluation nor regimen adjustment based on the evaluation results was allowed.
干预措施: Pertuzumab (Drug)
Cohort C
Patients who will receive surgery after completion of standard TCbHP regimen were be consecutively enrolled. Neither HER2-PET evaluation nor regimen adjustment based on the evaluation results was allowed.
干预措施: Trastuzumab (Herceptin) (Drug)
Cohort B
The initial treatment regimen consists of trastuzumab + pertuzumab + CDK4/6 inhibitor + aromatase inhibitor (AI) ± GnRHa. After two cycles, patients assessed as metabolic responders by HER2 PET continue the original regimen for a total of six cycles of dual HER2-antibody (HP), followed by surgery. Non-responders are switched to the TCbHP regimen for another six cycles, followed by surgery.
干预措施: Pertuzumab (Drug)
Cohort A
The initial treatment regimen is the TCbHP (Trastuzumab + Pertuzumab + Docetaxel/Nab-paclitaxel + Carboplatin). After two cycles, patients assessed as metabolic responders by HER2 PET continue the TCbHP regimen for a total of six cycles, followed by surgery. Metabolic non-responders are switched to either SHR-A1811 (4.8 mg intravenously every 21 days) or Trastuzumab Deruxtecan (T-DXd, 5.4 mg/kg intravenously every 21 days) for four cycles of intensified therapy.
干预措施: ADC (Drug)
Cohort B
The initial treatment regimen consists of trastuzumab + pertuzumab + CDK4/6 inhibitor + aromatase inhibitor (AI) ± GnRHa. After two cycles, patients assessed as metabolic responders by HER2 PET continue the original regimen for a total of six cycles of dual HER2-antibody (HP), followed by surgery. Non-responders are switched to the TCbHP regimen for another six cycles, followed by surgery.
干预措施: Trastuzumab (Herceptin) (Drug)
Cohort B
The initial treatment regimen consists of trastuzumab + pertuzumab + CDK4/6 inhibitor + aromatase inhibitor (AI) ± GnRHa. After two cycles, patients assessed as metabolic responders by HER2 PET continue the original regimen for a total of six cycles of dual HER2-antibody (HP), followed by surgery. Non-responders are switched to the TCbHP regimen for another six cycles, followed by surgery.
干预措施: carboplatin (Drug)
结局指标
主要结局
rate of pathologic complete response (pCR)
时间窗: Up to 6 months after treatment start
Proportion of participants who have no evidence by H\&E staining of residual invasive disease
次要结局
- SUVmax change on HER2-PET(Up to 6 months after treatment start)
研究者
xuliang
professor
Peking University Cancer Hospital & Institute