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

November 20, 2025 updated by: Wang Ouchen, First Affiliated Hospital of Wenzhou Medical University

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

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
302

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Zhejiang
      • Wenzhou, Zhejiang, China
        • The First Affiliated Hospital of Wenzhou Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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:

  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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pathological complete response rate（pCR）
Time Frame: 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)
Pathological diagnosis results were obtained tithin one month after the operation

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Objective response rate(ORR)
Time Frame: At the end of Cycle 8 (each cycle is 28 days)
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
Time Frame: Long-term follow-up monitoring was conducted until 3 years after enrollment
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
Time Frame: 1 year
Continuous monitoring, assessment and patient feedback.
1 year

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The breast-conserving rate of breast malignant tumor surgery
Time Frame: Perioperative/Periprocedural
The breast-conserving rate of breast malignant tumor surgery
Perioperative/Periprocedural

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
First Affiliated Hospital of Wenzhou Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 8, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 20, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 28, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 28, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 20, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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