Study on the Safety and Tolerability of Postoperative Radiotherapy Concurrent With CDK4/6 Inhibitors in HR+/HER2- High-Risk Breast Cancer

The investigators combined postoperative radiotherapy with CDK4/6 inhibitors ± endocrine adjuvant therapy to explore the tolerability and safety of this treatment regimen in HR+/HER2- postoperative high-risk breast cancer patients. During the study, investigators also utilized PRO scales (FACT-B, FACT-ES, FACT-F) to evaluate patients' multidimensional experiences, such as physical function, emotional state, and treatment-related symptoms, thereby obtaining more authentic and reliable data for symptom assessment and patient benefit.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: CDK4/6 inhibitor±endocrine therapy drug±OFS treatment combined with synchronous radiotherapy

Detailed Description

1. The screening and evaluation of patients are conducted within 28 days prior to their enrollment, with the investigator screening subjects who meet the inclusion criteria. Prior to initiating any study-specific procedures or assessments, it is mandatory to obtain a signed informed consent form (ICF) from the subjects. Suitable candidates are selected through a series of consultations and examinations, which include inquiries about the patient's personal information, medical history, family history, marital and reproductive history, postoperative pathology, electrocardiogram (ECG), CT scans, complete blood count (CBC), blood biochemistry, and other relevant laboratory tests, to determine whether the subjects are eligible for enrollment in this study.
2. The patient is orally administered the CDK4/6 inhibitor determined by the dose escalation model one day before radiotherapy. During radiotherapy, patient visits are conducted weekly (±2 days) to record vital signs, adverse reactions, and related management measures, specifically at the following times: 7 days before the start of radiotherapy, the 10th day of radiotherapy, the 20th day of radiotherapy, and the 30th day of radiotherapy. If the patient's radiotherapy is delayed for any reason, the follow-up time should be postponed according to the actual situation. PRO scale questionnaires (FACT-B, FACT-ES, FACT-F) are assessed one day before radiotherapy, on the 14th day of radiotherapy, and on the 28th day of radiotherapy. Follow-up evaluations and PRO scale questionnaire assessments are conducted 2 weeks and 4 weeks after the completion of the combined treatment regimen. After completing the 4-week follow-up period of the combination therapy, the patient may resume the normal oral dosage of CDK4/6 inhibitor medication.
3. Evaluate efficacy and safety through statistical methods to form research conclusions. Conduct data cleaning and preprocessing, safety analysis (incidence and severity of AEs; analysis of the correlation between serious adverse events and treatment), and summarize and report the results.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Yong Li; Phone Number: 86-13628566285; Email: liyong7229771@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age is 18-75 years old, gender is female

• Postoperative pathological examination confirmed HR+, HER2- invasive breast cancer:

  1. ER positivity and/or PR positivity is defined as: all positively stained tumor cells The proportion of tumor cells is ≥10%;
  2. HER2 negativity is defined as: 0/1+ by standard immunohistochemistry (IHC) test; ISH test was negative.
• The time from radical surgery or breast-conserving surgery to randomization shall not exceed 6 months;
• Postoperative pathological examination after radical surgery revealed the presence of lymph nodes in the axilla on the ipsilateral side of the breast lesion.

Metastasis (lymph node micrometastases, ipsilateral internal mammary lymph nodes and supraclavicular lymph nodes are allowed) metastasis, but the number of metastases to the ipsilateral internal mammary lymph nodes and supraclavicular lymph nodes is not included in the positive calculation of sexual lymph nodes), the specific requirements are as follows:

1) The number of lymph node metastases is ≥ 4; 2) When the number of lymph node metastases is 1 to 3, at least one of the following high-risk factors must be met: i. Postoperative pathological examination shows that the diameter of the primary tumor is ≥5cm; ii. The histological grade of the primary tumor is grade III (excluding grade II-III); iii. There is residual invasive cancer in breast lesions after neoadjuvant treatment; iv. Ki-67≥30%.

• Eastern Cooperative Oncology Group (ECOG) physical status score is 0 -2 points.
• With my consent and having signed the informed consent form, I am willing and able to comply with the planned interview.

inspections, study treatment plans, laboratory tests, and other research procedures.

Exclusion Criteria:

• Pathological examination diagnosed as HER2-positive breast cancer (HER2-positive definition: standard immune Histochemistry (IHC) test is 3+ or ISH test is positive).
• Local or regional recurrence of breast malignant tumors.
• The clinical stage of the tumor is stage IV (metastatic) breast cancer.
• Bilateral breast cancer (including contralateral carcinoma in situ).
• History of serious lung diseases such as interstitial pneumonia.
• Have received CDK4/6 inhibitor treatment or other anti-tumor biological treatments in the past therapy, targeted therapy or tumor immunotherapy.
• Have undergone major surgical operations, any investigational drugs, or others within 4 weeks before randomization Anticancer treatment or use of immunomodulators (excluding surgery, chemotherapy, radiotherapy and endocrine therapy).
• The presence of other serious physical or mental illnesses or laboratory abnormalities that may increase participation The risks of the research, or interference with the research results, and the researcher's opinion that he is not suitable to participate in this research study patients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Radiotherapy with concurrent CDK4/6 inhibitors combined with endocrine therapy; After the patient is confirmed to be enrolled, the CDK4/6i dose for the next patient is determined by a dose allocation model (empirical logistic model, obtained using the R dfcrm software package) based on the DLT observed in all previously evaluated patients. The starting dose of CDK4/6i (abexiclib, oral) is 50 mg bid, and other dose levels are: 100 mg bid, 150 mg bid.

Drug: CDK4/6 inhibitor±endocrine therapy drug±OFS treatment combined with synchronous radiotherapy; After the patient is confirmed to be enrolled, the CDK4/6i dose for the next patient is determined by a dose allocation model (empirical logistic model, obtained using the R dfcrm software package) based on the DLT observed in all previously evaluated patients. The starting dose of CDK4/6i (abexiclib, oral) is 50 mg bid, and other dose levels are: 100 mg bid, 150 mg bid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tolerability and safety	This study aims to investigate the tolerability and safety of postoperative adjuvant radiotherapy combined with CDK4/6 inhibitors in the treatment of hormone receptor-positive, HER2-negative high-risk breast cancer patients. Safety will be expressed by the incidence (%) of grade 3 and above adverse events during the course of treatment. Tolerability is expressed by the maximum dose (mg) of CDK4/6 inhibitor that the patient can use during the combination therapy.	From enrollment to 3 months after the end of radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the impact of this combination regimen on patient quality of life	The quality of life of patients was assessed using the FACT-B, FACT-ES, and FACIT-F scales at (the day before radiotherapy (T0), week 4 (T1), after radiotherapy (T2), 1 month after radiotherapy (T3), and 3 months after radiotherapy (T4)), respectively. The score and total score at each time point are calculated separately through three scales: FACT-B: total score ranges from 0 to 144 points. FACT-ES: Total score ranges from 0-180. FACIT-F: Total score ranges from 0-52 points. In the FACT-B, a higher total score represents a better quality of life. In the FACIT-F and FACT-ES, the higher the total score, the less fatigue and endocrine symptoms are.	Start of radiotherapy to 3 months after radiotherapy

Collaborators and Investigators

• Sponsor: Guizhou Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: November 22, 2025
• First Submitted That Met QC Criteria: February 25, 2026
• First Posted (Actual): March 3, 2026

Study Record Updates

• Last Update Posted (Actual): March 3, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: 2025-169

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