ctDNA-Guided De-Escalation of Adjuvant Chemotherapy With Dalpiciclib in HR-Positive/HER2-Negative Breast Cancer

Recruiting now · Phase 2

Conditions studied: Hormone Receptor-Positive Breast Cancer, High-risk Breast Cancer, Early-Stage Breast Cancer, HER2-negative Breast Cancer, ctDNA Monitoring, Breast Cancer Early Stage Breast Cancer (Stage 1-3)

In brief

* This is a Phase II, multicenter, randomized clinical trial evaluating a ctDNA-guided approach to de-escalate adjuvant chemotherapy in patients with hormone receptor (HR)-positive, HER2-negative early-stage breast cancer. The study aims to determine if combining the CDK4/6 inhibitor Dalpiciclib with endocrine therapy can reduce the need for chemotherapy while maintaining clinical benefits. * Key Details ： 1. Participants: 393 women (aged 18-75) with early-stage HR+/HER2- breast cancer at high risk of recurrence (e.g., tumor size ≥2 cm, lymph node involvement, or high-grade tumors). 2. Design: Patients are randomized 1:4 to two groups: Group A (Chemotherapy) : Receives 4 cycles of taxane-based chemotherapy before surgery. Group B (Experimental) : Receives Dalpiciclib + aromatase inhibitor (AI) for 4 cycles pre-surgery. Post-surgery, treatment is adjusted based on ctDNA results. 3. Primary Goals ： Assess ctDNA clearance rate (conversion from detectable to undetectable ctDNA) after neoadjuvant therapy in Group B. Evaluate 3-year event-free survival (EFS) in Group B (e.g., freedom from cancer recurrence, progression, or death). Secondary Goals ： Safety of Dalpiciclib + endocrine therapy. Tumor response rates (e.g., complete cell cycle arrest, pathological remission). Correlation between ctDNA clearance and long-term outcomes. * Why This Matters ： Current guidelines recommend chemotherapy for high-risk HR+ breast cancer, but it often causes significant side effects. This study explores a personalized approach using ctDNA-a blood-based biomarker-to identify patients who may safely avoid chemotherapy without compromising survival. If successful, it could shift clinical practice toward less toxic, targeted therapies for eligible patients.

Key facts

Study ID

NCT06970912

Run by

Peking University People's Hospital

People needed

393

Starts

2025-08-01

Expected to finish

2029-12-31

Last updated by the study team

2026-07-13

Who can join

Age: 18 and older, up to 75. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

• Female breast cancer patients aged ≥18 years and ≤75 years, either postmenopausal or premenopausal/perimenopausal;
• Pathologically confirmed hormone receptor-positive (HR+), HER2-negative invasive breast cancer:
• ER-positive and/or PR-positive defined as: ≥10% of tumor cells showing positive staining;
• HER2-negative defined as: standard immunohistochemistry (IHC) result of 0/1+; or IHC 2+ with negative in situ hybridization (ISH) (confirmed by the central pathology laboratory);
• At least one evaluable lesion per RECIST 1.1, with clinical staging meeting:
• T1c-2N0M0 with high-risk factors (Grade 3, or Grade 2 with Ki67 ≥20%);
• T3N0M0;
• Any TN+M0;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
• Willing to participate in the study and voluntarily sign informed consent;
• Agree to undergo ctDNA testing during treatment;
• Adequate organ and bone marrow function defined as:
• Absolute neutrophil count (ANC) ≥1,500/mm³ (1.5 × 10⁹/L) (without granulocyte colony-stimulating factor [G-CSF] treatment within 14 days);
• Platelet count (PLT) ≥100,000/mm³ (100 × 10⁹/L) (without corrective therapy within 7 days);
• Hemoglobin (Hb) ≥9 g/dL (90 g/L) (without corrective therapy within 7 days);
• Serum creatinine ≤1.5× upper limit of normal (ULN) or creatinine clearance ≥60 mL/min (without corrective therapy within 7 days);
• Total bilirubin (TBIL) ≤1.5×ULN (without corrective therapy within 7 days);
• Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤1.5×ULN (without corrective therapy within 7 days);
• Cardiac function: left ventricular ejection fraction (LVEF) ≥55%; QTc interval corrected by Fridericia's formula (QTcF) <470 msec on 12-lead ECG;
• Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization and agree to use non-hormonal contraception from informed consent signing until 2 months after the last treatment.

You may not qualify if…

• HER2-positive breast cancer confirmed by current pathological diagnosis;
• Inflammatory breast cancer;
• Stage IV (metastatic) breast cancer;
• Bilateral breast cancer;
• Prior history of breast cancer (including ductal carcinoma in situ or invasive breast cancer);
• Any prior antitumor therapy for the current breast cancer, including systemic therapies (endocrine, chemotherapy, immunotherapy, biological therapy) or local therapies (radiotherapy, vascular embolization, axillary lymph node biopsy);
• Diagnosis of any malignancy within 5 years prior to randomization, except cured cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma of the skin;
• History of severe pulmonary diseases (e.g., interstitial pneumonia);
• HIV infection, acquired immunodeficiency syndrome (AIDS), active hepatitis B (HBV DNA ≥500 IU/mL), hepatitis C (HCV antibody-positive with HCV RNA above the lower limit of detection), or co-infection with HBV and HCV;
• Within 6 months prior to randomization: myocardial infarction, severe/unstable angina, NYHA Class ≥II heart failure, ≥Grade 2 persistent arrhythmia (per NCI CTCAE v5.0), atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident (including transient ischemic attack), or symptomatic pulmonary embolism;
• Severe active infection within 4 weeks prior to randomization (requiring intravenous antibiotics, antifungals, or antivirals) or unexplained fever >38.5°C during screening/before first dose;
• Known allergy to any component of the study drugs;
• Current participation in another interventional drug clinical study;
• Pregnancy or lactation;
• Refusal to comply with follow-up;
• Other severe physical/mental illnesses or laboratory abnormalities that may increase study risk, interfere with results, or render the patient unsuitable per investigator judgment.

Where it is running

• Peking University People's Hospital — Beijing, Beijing Municipality, China (enrolling)

Full record on ClinicalTrials.gov

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