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

Wenzhou Medical University

Status and phase: Not yet enrolling; Phase 2

Conditions: HR+/HER2- Breast Cancer

Treatments: Drug: Immunotherapy (Sintilimab); Radiation: Neoadjuvant radiotherapy; Drug: Neoadjuvant Chemotherapy (NACT)

Study type: Interventional

Funder types: Other

Identifiers

NCT07254858

KY2025-301

Details and patient eligibility

About

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.

Enrollment: 302 estimated patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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。

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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302 participants in 2 patient groups

Chemotherapy+Immunotherapy

Experimental group

Description:

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.

Treatment:

Drug: Neoadjuvant Chemotherapy (NACT)

Drug: Immunotherapy (Sintilimab)

Chemotherapy + Immunotherapy + Radiotherapy

Experimental group

Description:

Neoadjuvant chemotherapy combined with immunotherapy（same as Arm1) + Neoadjuvant Radiotherapy

Treatment:

Drug: Neoadjuvant Chemotherapy (NACT)

Radiation: Neoadjuvant radiotherapy

Drug: Immunotherapy (Sintilimab)