Combined Chemo-immunotherapy Plus SBRT in Neoadjuvant Treatment for Luminal Subtype Breast Cancer: A Prospective Multicenter Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 302
- 试验地点
- 1
- 主要终点
- Pathological complete response rate（pCR）
研究概览
简要总结
This study is a prospective, randomized controlled clinical trial designed to evaluate the efficacy and safety of combining radiotherapy, chemotherapy, and immunotherapy in the neoadjuvant treatment of high-risk HR+/HER2- breast cancer patients.
The study plans to enroll treatment-naïve HR+/HER2- breast cancer patients aged 18-75 with high-risk features (e.g., tumor size ≥3 cm or lymph node positivity, Ki-67 ≥20%). Eligible subjects will be randomized in a 1:1 ratio into two groups: the control group will receive neoadjuvant chemotherapy (nab-paclitaxel followed by epirubicin + cyclophosphamide) in combination with sintilimab immunotherapy; the experimental group will receive the same chemotherapy and immunotherapy regimen with the addition of stereotactic body radiotherapy (SBRT) administered early during treatment, at a prescribed dose of 8 Gy per fraction for 3 fractions, with one fraction per day.
The study has dual primary endpoints: pathological complete response (pCR,) and objective response rate (ORR ). Secondary endpoints include 3-year event-free survival (EFS), incidence of adverse events (CTCAE v5.0), and postoperative cosmetic outcomes of the breast. The study design incorporates hierarchical testing to control for multiplicity, and long-term follow-up is planned to evaluate survival benefits.
The study has been approved by the ethics committee, and all participants are required to provide written informed consent. The results are expected to offer a novel neoadjuvant treatment strategy for high-risk HR+/HER2- breast cancer patients and improve their therapeutic outcomes.
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
- Single (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
- •Newly diagnosed, untreated breast cancer;
- •Age: 18 years ≤ age ≤ 75 years;
- •Histologically confirmed hormone receptor-positive (HR+) tumor specimen (estrogen receptor [ER] ≥ 10%);
- •Human epidermal growth factor receptor-2 immunohistochemistry (HER2-IHC) result of 0/1+ or 2+ with negative fluorescence in situ hybridization (FISH) test;
- •Histologically confirmed cell proliferation index (Ki67) ≥ 20%;
- •Programmed death-ligand 1 combined positive score (PD-L1 CPS) evaluable (i.e., availability of fresh/archived specimens);
- •Good pulmonary function;
- •Adequate hepatic and renal function;
- •Histological grade ≥ 2;
- •cN0, cT ≥ 3 cm or cN1-3, cT ≥ 2 cm (cT: clinically assessed maximum diameter of primary tumor; cN: clinically assessed regional lymph node status);
- •Eastern Cooperative Oncology Group Performance Status (ECOG score) 0-1.
排除标准
- •1.Pregnancy; 2.Tumor > 8 cm with skin ulceration; 3.History of thoracic radiotherapy or contraindications to radiotherapy; 4.Active autoimmune disease; 5.Prior use of PD-L1 antibody therapy; 6.De novo breast cancer; 7.There are factors that may significantly increase the risk of lung or cardiac toxicity related to radiotherapy, such as (1) maximum lung depth(MLD) >3.2cm； (2) maximum heart distance(MHD) <2.4cm。
研究组 & 干预措施
Chemotherapy+Immunotherapy
Control Group: Neoadjuvant chemotherapy combined with immunotherapy, wherein the neoadjuvant chemotherapy regimen follows the clinical standard protocol.
Neoadjuvant Chemotherapy Regimen:
A sequential chemotherapy strategy is adopted, with the specific regimen as follows:
Taxane-based Chemotherapy Phase (T Phase):
Nab-paclitaxel (125 mg/m²), administered by intravenous infusion on Day 1 and Day 8 of each 21-day cycle (Q3W), for a total of 4 cycles.
Anthracycline-based Combination Chemotherapy Phase (EC Phase):
Epirubicin (75-100 mg/m²) in combination with cyclophosphamide (600 mg/m²), administered by intravenous infusion every 21 days (Q3W), for a total of 4 cycles.
The EC phase commences upon completion of the T phase.
Immunotherapy Regimen:
Sintilimab (200 mg), administered by intravenous infusion every three weeks (Q3W).
Dosing begins on Day 2 of the chemotherapy cycles, for a total of 8 treatment cycles.
干预措施: Neoadjuvant Chemotherapy (NACT) (Drug)
Chemotherapy+Immunotherapy
Control Group: Neoadjuvant chemotherapy combined with immunotherapy, wherein the neoadjuvant chemotherapy regimen follows the clinical standard protocol.
Neoadjuvant Chemotherapy Regimen:
A sequential chemotherapy strategy is adopted, with the specific regimen as follows:
Taxane-based Chemotherapy Phase (T Phase):
Nab-paclitaxel (125 mg/m²), administered by intravenous infusion on Day 1 and Day 8 of each 21-day cycle (Q3W), for a total of 4 cycles.
Anthracycline-based Combination Chemotherapy Phase (EC Phase):
Epirubicin (75-100 mg/m²) in combination with cyclophosphamide (600 mg/m²), administered by intravenous infusion every 21 days (Q3W), for a total of 4 cycles.
The EC phase commences upon completion of the T phase.
Immunotherapy Regimen:
Sintilimab (200 mg), administered by intravenous infusion every three weeks (Q3W).
Dosing begins on Day 2 of the chemotherapy cycles, for a total of 8 treatment cycles.
干预措施: Immunotherapy (Sintilimab) (Drug)
Chemotherapy + Immunotherapy + Radiotherapy
Neoadjuvant chemotherapy combined with immunotherapy（same as Arm1) + Neoadjuvant Radiotherapy
干预措施: Neoadjuvant radiotherapy (Radiation)
Chemotherapy + Immunotherapy + Radiotherapy
Neoadjuvant chemotherapy combined with immunotherapy（same as Arm1) + Neoadjuvant Radiotherapy
干预措施: Neoadjuvant Chemotherapy (NACT) (Drug)
Chemotherapy + Immunotherapy + Radiotherapy
Neoadjuvant chemotherapy combined with immunotherapy（same as Arm1) + Neoadjuvant Radiotherapy
干预措施: Immunotherapy (Sintilimab) (Drug)
结局指标
主要结局
Pathological complete response rate（pCR）
时间窗: Pathological diagnosis results were obtained tithin one month after the operation
Postoperative pathological assessment (tumor Miller-Payne system grading and axillary lymph node pathological assessment)
次要结局
- Objective response rate(ORR)(At the end of Cycle 8 (each cycle is 28 days))
- Event-free survival rate(Long-term follow-up monitoring was conducted until 3 years after enrollment)
- Incidence of adverse reactions(1 year)
研究者
Wang Ouchen
Chief Physician
First Affiliated Hospital of Wenzhou Medical University