Combined Chemo-immunotherapy Plus SBRT in Neoadjuvant Treatment for Luminal Subtype Breast Cancer

NCT ID: NCT07254858

Last Updated: 2025-11-28

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 302 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-31
• Study Completion Date: 2029-12-30

Brief Summary

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.

Conditions

HR+/HER2- Breast Cancer

Keywords

Breast Cancer; Radiotherapy; Immunotherapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Neoadjuvant Chemotherapy (NACT)

Intervention Type: DRUG

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 (Sintilimab)

Intervention Type: DRUG

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.

Chemotherapy + Immunotherapy + Radiotherapy

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

Group Type: EXPERIMENTAL

Neoadjuvant radiotherapy

Intervention Type: RADIATION

Neoadjuvant Radiotherapy Regimen:

1. 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

2. Radiotherapy Schedule: Irradiation begins on the second day of the first chemotherapy cycle and is administered every other day

3. Target Volume Definition: The radiotherapy target volume is defined based on baseline imaging (e.g., CT, MRI, or PET-CT)

4. 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

Neoadjuvant Chemotherapy (NACT)

Intervention Type: DRUG

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 (Sintilimab)

Intervention Type: DRUG

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.

Interventions

Neoadjuvant radiotherapy

Neoadjuvant Radiotherapy Regimen:

1. 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

2. Radiotherapy Schedule: Irradiation begins on the second day of the first chemotherapy cycle and is administered every other day

3. Target Volume Definition: The radiotherapy target volume is defined based on baseline imaging (e.g., CT, MRI, or PET-CT)

4. 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

Intervention Type: RADIATION

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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);

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。

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital of Wenzhou Medical University

OTHER

Sponsor Role: lead

Responsible Party

Wang Ouchen

Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Countries

China

Facility Contacts

Professor Wang

Role: primary

Other Identifiers

KY2025-301

Identifier Type: -

Identifier Source: org_study_id