Dalpiciclib with endocrine therapy, with or without low‑dose capecitabine, for HR+/HER2‑ advanced breast cancer with organ (visceral) spread

Open, Randomized Controlled Study of Dalpiciclib Combined With Endocrine Therapy and Metronomic Capecitabine Versus Dalpiciclib Combined With Endocrine Therapy for HR +/HER2- Recurrent Metastatic Breast Cancer With Visceral Metastasis

This trial tests whether adding continuous low‑dose (metronomic) capecitabine to dalpiciclib plus endocrine therapy helps women with HR+/HER2‑ advanced breast cancer that has spread to organs.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 258 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Fujian Cancer Hospital (Government)
• Drugs / interventions: radiation, chemotherapy
• Locations: 1 site (Fuzhou, Fujian)
• Trial ID: NCT07467330 on ClinicalTrials.gov

What this trial studies

This is an open‑label, multicenter, randomized Phase 3 trial enrolling about 258 patients with HR+/HER2‑ advanced breast cancer and visceral metastases. Participants are randomized 1:1 to receive dalpiciclib plus endocrine therapy with metronomic capecitabine versus dalpiciclib plus endocrine therapy alone. Randomization is stratified by number of prior lines for recurrent metastases (0 versus 1) and by the chosen endocrine therapy (aromatase inhibitor versus fulvestrant). The trial compares clinical outcomes and safety of adding continuous low‑dose oral capecitabine to a CDK4/6 inhibitor plus endocrine backbone.

Who should consider this trial

Good fit: Women aged 18 or older with HR+/HER2‑ advanced breast cancer that is not curable by surgery or radiotherapy and with visceral metastases who meet the menopausal status and treatment‑willingness criteria are the intended participants.

Not a fit: Patients who are HER2‑positive, who do not have visceral metastases, who cannot take oral chemotherapy or CDK4/6 inhibitors, or who do not meet the menopausal/LHRH requirements are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, adding metronomic capecitabine could improve disease control or delay progression compared with dalpiciclib plus endocrine therapy alone.

How similar studies have performed: CDK4/6 inhibitors combined with endocrine therapy are proven effective in HR+/HER2‑ advanced breast cancer, but adding metronomic capecitabine to this combination is less well tested and remains exploratory.

Eligibility criteria

Inclusion Criteria:

1. postmenopausal or premenopausal/perimenopausal women ≥ 18 years of age who meet one of the following: a) prior bilateral oophorectomy, or ≥ 60 years of age; or b) age \< 60 years, spontaneous postmenopausal status (defined as spontaneous cessation of regular menstruation for at least 12 consecutive months without other pathological or physiological causes), E2 and FSH at postmenopausal levels; or c) premenopausal or perimenopausal women must be willing to receive LHRH agonists between studies.
2. Female breast cancer patients diagnosed as HR positive and HER2 negative by pathological examination are not suitable for surgical resection or radiation therapy with the purpose of cure.

   A) ER-positive and/or PR-positive are defined as having positively stained tumor cells representing ≥ 1% of all tumor cells (reviewed and confirmed by the investigator at the site); b) HER2-negative are defined as having 0/1 + by standard immunohistochemistry (IHC); HER2/CEP17 ratio of less than 2.0 by ISH or HER2 gene copy number of less than 4 (reviewed and confirmed by the investigator at the site).
3. ECOG score 0-2.
4. Patients with new stage IV or recurrent metastases with visceral metastases are allowed to enroll patients with visceral crisis (visceral crisis definition includes but is not limited to meeting one of the following: pleural effusion; ascites; abdominal pain caused by liver or peritoneal metastases; rapid worsening of dyspnea at rest that cannot be relieved by pleural effusion drainage; rapid increase in bilirubin \> 1.5 × ULN in the absence of Gilbert 's syndrome or biliary obstruction).
5. adequate bone marrow function, defined as follows: a) neutrophil count (ANC) ≥ 1,500/mm3 (1.5 x 109 L) (no growth factors used within 14 days); b) platelet count (PLT) ≥ 100,000/mm3 (100 x 109 L) (no corrective treatment used within 7 days); c) hemoglobin (Hb) ≥ 8 g/dL (80 g/L) (no corrective treatment used within 14 days).
6. Female subjects who are not postmenopausal or surgically sterile must have a negative serum pregnancy test within 7 days before the first dose and are willing to abstain from sexual intercourse or use a medically recognized highly effective contraceptive measure after signing informed consent, during the study, and for 1 year after the last dose of study drug.
7. Voluntarily join this study, sign informed consent, have good compliance and are willing to cooperate with follow-up.

Exclusion Criteria:

1. patients who have previously been treated with CDK4/6 inhibitors and/or capecitabine.
2. patients who relapse within 2 years of adjuvant endocrine therapy.
3. Patients with bone metastases alone regardless of recurrence, metastasis or new stage IV disease.
4. patients with active brain metastases.
5. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), hepatitis B surface antigen positive and HBV DNA ≥ 2000 IU/ml, hepatitis C (hepatitis C antibody positive, and HCV-RNA above the lower limit of detection of the analytical method) or combined hepatitis B and hepatitis C co-infection.
6. The following conditions occurred 6 months before enrollment: myocardial infarction, severe/unstable angina pectoris, NYHA class 2 or higher cardiac insufficiency, ≥ grade 2 persistent arrhythmia (according to NCI CTCAE version 5.0), atrial fibrillation of any grade, coronary/peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident (including transient ischemic attack) or symptomatic pulmonary embolism, and new thrombosis.
7. Complicated with severe infection within 4 weeks before the first dose (such as intravenous drip of antibiotics, antifungal or antiviral drugs according to clinical diagnosis and treatment specifications), or unexplained fever \> 38.5℃ during screening/before the first dose.
8. inability to swallow, bowel obstruction, or the presence of other factors that affect the administration and absorption of the drug.
9. known hypersensitivity to regimen combination therapy drugs and any of their excipients.
10. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
11. Known history of psychotropic substance abuse or drug abuse.
12. Female patients who are pregnant or lactating.
13. Any other condition that the investigator considers the subject unsuitable for participation in this study.

Where this trial is running

Fuzhou, Fujian

• Fujian Cancer Hosptial — Fuzhou, Fujian, China (Recruiting)

Study contacts

• Study coordinator: Chuangui Song

Conditions Breast Cancer