Combined Chemo-immunotherapy Plus SBRT in Neoadjuvant Treatment for Luminal Subtype Breast Cancer (CISN-L)

Combined Chemo-immunotherapy Plus SBRT in Neoadjuvant Treatment for Luminal Subtype Breast Cancer: A Prospective Multicenter Randomized Controlled Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: HR+/HER2- Breast Cancer
• Intervention / Treatment: Drug: Neoadjuvant Chemotherapy (NACT); Drug: Immunotherapy (Sintilimab); Radiation: Neoadjuvant radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 302
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Wenzhou, Zhejiang, China
      • The First Affiliated Hospital of Wenzhou Medical University
      • Contact: Professor Wang; Phone Number: 86+13957706099; Email: woc099@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Newly diagnosed, untreated breast cancer;
2. Age: 18 years ≤ age ≤ 75 years;
3. Histologically confirmed hormone receptor-positive (HR+) tumor specimen (estrogen receptor [ER] ≥ 10%);
4. Human epidermal growth factor receptor-2 immunohistochemistry (HER2-IHC) result of 0/1+ or 2+ with negative fluorescence in situ hybridization (FISH) test;
5. Histologically confirmed cell proliferation index (Ki67) ≥ 20%;
6. Programmed death-ligand 1 combined positive score (PD-L1 CPS) evaluable (i.e., availability of fresh/archived specimens);
7. Good pulmonary function;
8. Adequate hepatic and renal function;
9. Histological grade ≥ 2;
10. 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);
11. Eastern Cooperative Oncology Group Performance Status (ECOG score) 0-1. Exclusion Criteria:

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。

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Neoadjuvant Chemotherapy (NACT); 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.; Drug: Immunotherapy (Sintilimab); 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.
Experimental: Chemotherapy + Immunotherapy + Radiotherapy; Neoadjuvant chemotherapy combined with immunotherapy（same as Arm1) + Neoadjuvant Radiotherapy	Drug: Neoadjuvant Chemotherapy (NACT); 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.; Drug: Immunotherapy (Sintilimab); 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.; Radiation: Neoadjuvant radiotherapy; Neoadjuvant Radiotherapy Regimen: Radiotherapy Technique: Stereotactic Body Radiation Therapy (SBRT) Radiation Dose and Fractionation: 8 Gy per fraction, for a total of 3 fractions, amounting to a total dose of 24 Gy; Radiotherapy Schedule: Irradiation begins on the second day of the first chemotherapy cycle and is administered every other day; Target Volume Definition: The radiotherapy target volume is defined based on baseline imaging (e.g., CT, MRI, or PET-CT); Radiotherapy Equipment and Planning: Treatment is delivered using a linear accelerator equipped with Image-Guided Radiotherapy (IGRT) technology to ensure precise irradiation and dose optimization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response rate（pCR）	Postoperative pathological assessment (tumor Miller-Payne system grading and axillary lymph node pathological assessment)	Pathological diagnosis results were obtained tithin one month after the operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate(ORR)	The proportion of patients achieving complete response (CR) and partial response (PR) after tumor treatment was used as the second endpoint of the primary endpoint for hierarchical testing.	At the end of Cycle 8 (each cycle is 28 days)
Event-free survival rate	The time from randomization to the event (recurrence, metastasis or death)	Long-term follow-up monitoring was conducted until 3 years after enrollment
Incidence of adverse reactions	Continuous monitoring, assessment and patient feedback.	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The breast-conserving rate of breast malignant tumor surgery	The breast-conserving rate of breast malignant tumor surgery	Perioperative/Periprocedural

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Wenzhou Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: September 8, 2025
• First Submitted That Met QC Criteria: November 20, 2025
• First Posted (Actual): November 28, 2025

Study Record Updates

• Last Update Posted (Actual): November 28, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Breast Cancer; Immunotherapy; Radiotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Therapeutics; Biological Therapy; Combined Modality Therapy; Immunomodulation; Neoadjuvant Therapy; Immunotherapy; sintilimab
• Other Study ID Numbers: KY2025-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No