Brain Radiotherapy Combined With Dalpiciclib and Endocrine Therapy in HR-Positive/HER2-Negative Advanced Breast Cancer With Brain Metastases

NCT07539753 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: NFEC-2025-640
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, open-label, exploratory clinical trial designed to evaluate the efficacy and safety of brain radiotherapy combined with dalpiciclib and endocrine therapy in HR-positive/HER2-negative advanced breast cancer patients with brain metastases. A total of 46 patients are planned to be enrolled. Participants will receive dalpiciclib plus endocrine therapy and brain radiotherapy, including fractionated stereotactic radiotherapy (FSRT) or whole-brain radiotherapy (WBRT), according to the clinical characteristics of brain metastatic lesions. Radiotherapy may start within 30 days before or after initiation of drug treatment. Dalpiciclib and endocrine therapy may be given concurrently during radiotherapy and will be continued after radiotherapy until disease progression, intolerable toxicity, withdrawal of informed consent, or investigator decision. Participants will visit the clinic once every 3 months for checkups and tests. Tumor response will be assessed according to RECIST version 1.1, and safety will be evaluated throughout the study.

Conditions

Breast Cancer; Brain Metastases; HR+/HER2- Breast Cancer

Keywords

HR+/HER2- Breast Cancer; brain metastases; brain radiotherapy; dalpiciclib

Outcome Measures

Primary Outcomes (1)

• Central Nervous System Progression-Free Survival (CNS-PFS)

  CNS-PFS is measured from the date of first study treatment to the date of intracranial disease progression or death, whichever occurs first.

  12 months

Secondary Outcomes (4)

• Central Nervous System Objective Response Rate (CNS-ORR)

  12 months

• Progression-Free Survival (PFS)

  12 months

• Overall Survival (OS)

  12 months

• Incidence of Adverse Events

  12 months

Study Arms (1)

Dalpiciclib + Endocrine Therapy + Brain Radiotherapy

EXPERIMENTAL

Participants will receive dalpiciclib, endocrine therapy, and brain radiotherapy (FSRT or WBRT).

Drug: Dalpiciclib; Drug: Endocrine Therapy of Physician's Choice; Radiation: Brain Radiotherapy

Interventions

Dalpiciclib DRUG

Dalpiciclib will be administered orally at 125 mg once daily for 21 days followed by 7 days off in a 28-day cycle.

Dalpiciclib + Endocrine Therapy + Brain Radiotherapy

Endocrine Therapy of Physician's Choice DRUG

Endocrine therapy will be selected by the treating physician according to clinical practice.

Dalpiciclib + Endocrine Therapy + Brain Radiotherapy

Brain Radiotherapy RADIATION

Brain radiotherapy will include fractionated stereotactic radiotherapy (FSRT) or whole-brain radiotherapy (WBRT), according to the number, size, location, and distribution of brain metastatic lesions.

Dalpiciclib + Endocrine Therapy + Brain Radiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients aged 18 to 75 years, who are postmenopausal or premenopausal/perimenopausal, and meet at least one of the following conditions:
• prior bilateral oophorectomy; or age ≥60 years; or
• age \<60 years and postmenopausal status defined as at least 12 consecutive months of spontaneous amenorrhea without other pathological or physiological causes, with estradiol (E2) and follicle-stimulating hormone (FSH) levels within the postmenopausal range; or
• premenopausal or perimenopausal women are also eligible if they are willing to receive treatment with an LHRH agonist during the study.
• Histologically or cytologically confirmed HR-positive, HER2-negative breast cancer in female patients, with evidence of locally recurrent or metastatic disease that is not amenable to curative surgery or radiotherapy, and with no clinical indication for chemotherapy.
• HR-positive is defined as ER-positive and/or PR-positive, with ≥1% of tumor cells showing positive staining, as confirmed by the investigator at the study site.
• HER2-negative is defined as IHC 0 or 1+, or ISH-negative, defined as a HER2/CEP17 ratio \<2.0 or an average HER2 copy number \<4.0, as confirmed by the investigator at the study site.
• Presence of brain metastases confirmed by MRI, with at least one measurable intracranial lesion ≥1 cm according to RECIST version 1.1. Measurable extracranial disease is not required.
• ECOG performance status 0-2, and an estimated life expectancy of at least 12 weeks at the time of enrollment.
• If the patient is receiving corticosteroids, the corticosteroid dose must be stable or decreasing for at least 5 days before the brain gadolinium-enhanced MRI (Gd-MRI). This MRI must be performed within 28 days before enrollment. Patients who require an increased steroid dose before treatment, or who are receiving an unstable steroid dose, are not eligible.
• Screening laboratory values must meet the following criteria( and should be obtained within 14 days prior to registration)::
• absolute neutrophil count (ANC) ≥ 1,500/mm³ (1.5 × 10\^9/L), without growth factor support within 14 days;
• platelet count (PLT) ≥ 100,000/mm³ (100 × 10\^9/L), without corrective treatment within 7 days;
• hemoglobin (Hb) ≥ 9 g/dL (90 g/L), without corrective treatment within 7 days;
• serum creatinine (Scr) ≤ 1.5 × upper limit of normal (ULN), or creatinine clearance ≥ 60 mL/min;

You may not qualify if:

• Prior pathological diagnosis of HER2-positive breast cancer.
• Prior disease progression on dalpiciclib in the metastatic setting.
• Primary endocrine resistance, defined as either:
• disease recurrence or progression within 2 years of starting adjuvant endocrine therapy; or
• disease progression within 6 months of first-line endocrine therapy for advanced or metastatic disease.
• Patients considered not suitable for endocrine therapy in the judgment of the investigator, including patients with symptomatic visceral disease, disseminated visceral involvement, or a risk of life-threatening complications in the short term, such as uncontrolled massive effusions (pleural, pericardial, or peritoneal), lymphangitic carcinomatosis of the lung, or \>50% liver involvement.
• Presence of leptomeningeal metastases.
• Prior whole-brain radiotherapy (WBRT) .
• Any severe neurologic symptoms caused by central nervous system metastases.
• Pregnant or breastfeeding women.
• Any serious uncontrolled clinical disease or infection that, in the investigator's judgment, cannot be adequately controlled with appropriate treatment or may impair the patient's ability to tolerate study treatment, including but not limited to:
• serious cardiovascular events such as syncope of cardiovascular origin, pathologic ventricular arrhythmias (including but not limited to ventricular tachycardia or ventricular fibrillation), or cardiac arrest;
• end-stage renal disease;
• severe liver disease;
• active systemic bacterial infection.

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead
• Jiangmen Central Hospital: collaborator
• Dongguan People's Hospital: collaborator
• Sun Yat-Sen University Cancer Center: collaborator
• Fifth Affiliated Hospital, Sun Yat-Sen University: collaborator
• Meizhou People's Hospital: collaborator

Study Sites (1)

Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms

Interventions

dalpiciclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Central Study Contacts

Guangyu Yao, MD PhD

CONTACT

+86-13570966868; yaogy@sum.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2026
• First Posted: April 20, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)