[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100053974":3},{"organization":4,"outcomesModule":7,"designInfo":35,"detailedDescription":42,"studyPopulation":34,"armGroups":43,"interventions":50,"overallOfficials":55,"centralContacts":59,"locations":65,"responsibleParty":82,"collaborators":34,"id":85,"slug":86,"hasResults":87,"nctId":88,"briefTitle":89,"officialTitle":90,"acronym":91,"eligibilityCriteria":92,"healthyVolunteers":87,"sex":93,"minAge":94,"maxAge":95,"enrollmentInfo":96,"targetDuration":34,"studyType":99,"phases":100,"briefSummary":102,"conditions":103,"keywords":34,"overallStatus":67,"whyStopped":34,"lastUpdateSubmitDate":109,"lastUpdatePostDateStruct":110,"startDateStruct":113,"completionDateStruct":115,"leadSponsor":117,"locationsCount":118},{"fullName":5,"class":6},"Peking University People's Hospital","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":34},[9],{"measure":10,"description":11,"timeFrame":12},"ctDNA Clearance Rate after Neoadjuvant Therapy","Proportion of patients achieving conversion from detectable to undetectable ctDNA in plasma after 4 cycles of neoadjuvant CDK4\u002F6i+endocronetherapy. ctDNA analysis uses tumor-informed personalized panels (tracking 16 clonal variants via whole-exome sequencing), with clearance defined as ≥2 consecutive negative results at 1% variant allele frequency threshold.","From baseline to 4 weeks post-neoadjuvant therapy (pre-surgery)",[14,18,22,26,30],{"measure":15,"description":16,"timeFrame":17},"3-Year Event-Free Survival (EFS)","Time from randomization to first occurrence of locoregional\u002Fdistant recurrence, contralateral breast cancer, secondary malignancy, or death from any cause. Assessed via imaging (CT\u002FMRI), pathology, and clinical exams every 3 months for 3 years. Events are adjudicated by blinded independent review committee.","From neoadjuvant therapy to 36 months post-surgery",{"measure":19,"description":20,"timeFrame":21},"Residual Cancer Burden (RCB) 0-1 Rate","Proportion of patients achieving RCB 0 (pathological complete response) or RCB-1 (minimal residual disease) in surgical specimens. RCB is calculated using standardized criteria (tumor bed area, cellularity, nodal involvement) by blinded central pathology review.","At surgery (approximately 16 weeks since neoadjuvant therapy)",{"measure":23,"description":24,"timeFrame":25},"Objective Response Rate (ORR) by RECIST 1.1","Proportion of patients with complete\u002Fpartial response per RECIST 1.1 criteria during neoadjuvant phase, measured by MRI\u002FCT. Target lesion size reduction ≥30% (partial) or disappearance (complete) required, confirmed by two consecutive assessments ≥4 weeks apart.","Baseline to pre-surgery (week 16)",{"measure":27,"description":28,"timeFrame":29},"Complete Cell Cycle Arrest (CCCA) Rate (Ki67 ≤2.7%)","Percentage of patients with Ki67 ≤2.7% in post-neoadjuvant tumor biopsies, assessed via immunohistochemistry (IHC) with 3,3'-diaminobenzidine staining. Central laboratory quantification uses Aperio image analysis system (Leica Biosystems).","Post-neoadjuvant therapy (pre-surgery, week 16)",{"measure":31,"description":32,"timeFrame":33},"Incidence of Grade ≥3 Treatment-Related Adverse Events (TRAEs)","Proportion of patients experiencing grade ≥3 adverse events (per NCI CTCAE v5.0) related to Dalpiciclib + AI or chemotherapy, including hematologic (neutropenia, anemia), hepatic (ALT\u002FAST elevation), and cardiac (LVEF decline ≥10%) toxicities. Events are monitored every cycle during neoadjuvant therapy and quarterly during adjuvant phase.","From first dose to 30 days after last treatment",null,{"allocation":36,"interventionModel":37,"interventionModelDescription":38,"primaryPurpose":39,"observationalModel":34,"timePerspective":34,"maskingInfo":40},"NA","SINGLE_GROUP","All patients receives oral CDK4\u002F6 inhibitor combined with endocrine therapy.","TREATMENT",{"masking":41,"maskingDescription":34,"whoMasked":34},"NONE","Breast cancer remains a leading cause of cancer-related morbidity and mortality globally, with hormone receptor-positive (HR+), HER2-negative (HER2-) subtypes accounting for approximately 70% of cases. While adjuvant chemotherapy is standard for high-risk early-stage HR+\u002FHER2- breast cancer, it carries significant toxicity, and many patients may not derive clinical benefit. Emerging evidence suggests that circulating tumor DNA (ctDNA)-a minimally invasive biomarker reflecting residual disease-may guide personalized treatment de-escalation.\n\nPreclinical and clinical studies demonstrate that ctDNA dynamics correlate with tumor burden and prognosis. In HR+ breast cancer, ctDNA clearance after neoadjuvant therapy is associated with improved survival, while persistent ctDNA post-treatment predicts recurrence. CDK4\u002F6 inhibitors, such as Dalpiciclib, have revolutionized advanced HR+\u002FHER2- breast cancer management by enhancing endocrine therapy efficacy. However, their role in early-stage disease, particularly in a ctDNA-guided de-escalation strategy, remains underexplored. This study addresses this gap by evaluating whether ctDNA-driven decision-making can safely reduce chemotherapy use while maintaining clinical outcomes.\n\nStudy Objectives Primary Objectives: Assess ctDNA clearance rate (defined as conversion from detectable to undetectable ctDNA) after 4 cycles of neoadjuvant CDK4\u002F6i + endocrine therapy.\n\nSecondary Objectives Evaluate 3-year event-free survival (EFS), where events include local\u002Fdistant recurrence, secondary malignancies, or death.\n\nCompare safety profiles of CDK4\u002F6i + endocrine therapy versus chemotherapy.\n\nEvaluate tumor response metrics:\n\nPathological complete response (pCR) and residual cancer burden (RCB 0-1). Complete cell cycle arrest (CCCA; Ki67 ≤2.7%). Assess objective response rate (ORR) by RECIST 1.1.\n\nExploratory Objectives Correlate ctDNA clearance with long-term outcomes (e.g., EFS, overall survival).\n\nStudy Design\n\nAll patients received 4 cycles of neoadjuvant CDK4\u002F6i + endocrine therapy. Post-Surgery Treatment： ctDNA-negative post-neoadjuvant: Continue CDK4\u002F6i + endocrine therapy ctDNA-positive post-neoadjuvant: Optional adjuvant chemotherapy followed by CDK4\u002F6i + endocrine therapy.",[44],{"label":45,"type":46,"description":47,"interventionNames":48},"CDK4\u002F6 inhibitor with endocrine therapy","EXPERIMENTAL","Patients receive 4 cycles of neoadjuvant CDK4\u002F6 inhibitor with endocrine therapy. Post-surgery treatment is guided by ctDNA status:\n\nctDNA-negative at baseline and post-neoadjuvant, with post-op Ki67 ≤10% ：Continue CDK4\u002F6 inhibitor with endocrine therapy for 2-3 years.\n\nctDNA-positive → negative, or persistently ctDNA-negative with post-op Ki67 \\>10% :\n\nRandomized 1:1 to:\n\nArm 1: CDK4\u002F6 inhibitor with endocrine therapy for 2-3 years. Arm 2: Adjuvant chemotherapy (investigator's choice) → CDK4\u002F6 inhibitor with endocrine therapy for 2-3 years.\n\n（3）Persistently ctDNA-positive or ctDNA-negative → positive: Adjuvant chemotherapy → CDK4\u002F6 inhibitor with endocrine therapy for 2-3 years.\n\nPremenopausal women receive ovarian suppression with LHRH agonists.",[49],"Drug: CDK4\u002F6 inhibitor with endocrine therapy",[51],{"type":52,"name":45,"description":53,"armGroupLabels":54,"otherNames":34},"DRUG","CDK4\u002F6 inhibitor with endocrine therapy for neoadjuvent therapy",[45],[56],{"name":57,"affiliation":5,"role":58},"shu wang, doctor","PRINCIPAL_INVESTIGATOR",[60],{"name":61,"role":62,"phone":63,"phoneExt":34,"email":64},"yuan peng, doctor","CONTACT","86+13671287670","13671287670@163.com",[66],{"facility":5,"status":67,"city":68,"state":69,"zip":70,"country":71,"countryCode":72,"cosmosGeoPoint":73,"geoPoint":78,"contacts":79},"RECRUITING","Beijing","Beijing Municipality","100044","China","CN",{"type":74,"coordinates":75},"Point",[76,77],116.39723,39.9075,{"lat":77,"lon":76},[80],{"name":81,"role":62,"phone":63,"phoneExt":34,"email":64},"yuan peng, Doctor",{"type":58,"investigatorFullName":83,"investigatorTitle":84,"investigatorAffiliation":5,"oldNameTitle":34,"oldOrganization":34},"Shu Wang","director of breast center","100053974","phase-2-cdk46-inhibitors-combined-with-endocrine-therapy-for-neoadjuvant-treatment-100053974",false,"NCT07366112","CDK4\u002F6 Inhibitors Combined With Endocrine Therapy for Neoadjuvant Treatment","CDK4\u002F6 Inhibitors Combined With Endocrine Therapy for Neoadjuvant Treatment of Breast Cancer: ctDNA-Guided Personalized Therapy","DNACDKHR","Inclusion Criteria:\n\n* 1.Female breast cancer patients aged ≥18 years and ≤75 years, either postmenopausal or premenopausal\u002Fperimenopausal; 2.Pathologically confirmed hormone receptor-positive (HR+), HER2-negative invasive breast cancer:\n\n  1. ER-positive and\u002For PR-positive defined as: ≥10% of tumor cells showing positive staining;\n  2. HER2-negative defined as: standard immunohistochemistry (IHC) result of 0\u002F1+; or IHC 2+ with negative in situ hybridization (ISH) (confirmed by the central pathology laboratory); 3. At least one evaluable lesion per RECIST 1.1, with clinical staging meeting:\n\n  \u003C!-- -->\n\n  1. T1c-2N0M0 with high-risk factors (Grade 3, or Grade 2 with Ki67 ≥20%);\n  2. T3N0M0;\n  3. Any TN+M0; 4.Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1; 5.Willing to participate in the study and voluntarily sign informed consent; 6.Agree to undergo ctDNA testing during treatment; 7.Adequate organ and bone marrow function defined as:\n\n  \u003C!-- -->\n\n  1. Absolute neutrophil count (ANC) ≥1,500\u002Fmm³ (1.5 × 10⁹\u002FL) (without granulocyte colony-stimulating factor \\[G-CSF\\] treatment within 14 days);\n  2. Platelet count (PLT) ≥100,000\u002Fmm³ (100 × 10⁹\u002FL) (without corrective therapy within 7 days);\n  3. Hemoglobin (Hb) ≥9 g\u002FdL (90 g\u002FL) (without corrective therapy within 7 days);\n  4. Serum creatinine ≤1.5× upper limit of normal (ULN) or creatinine clearance ≥60 mL\u002Fmin (without corrective therapy within 7 days);\n  5. Total bilirubin (TBIL) ≤1.5×ULN (without corrective therapy within 7 days);\n  6. Aspartate aminotransferase (AST\u002FSGOT) and alanine aminotransferase (ALT\u002FSGPT) ≤1.5×ULN (without corrective therapy within 7 days);\n  7. Cardiac function: left ventricular ejection fraction (LVEF) ≥55%; QTc interval corrected by Fridericia's formula (QTcF) \\\u003C470 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.\n\nExclusion Criteria:\n\n* 1.Bilateral breast cancer; 2.Prior history of breast cancer (including ductal carcinoma in situ or invasive breast cancer); 3.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); 4.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; 5.History of severe pulmonary diseases (e.g., interstitial pneumonia); 6. HIV infection, acquired immunodeficiency syndrome (AIDS), active hepatitis B (HBV DNA ≥500 IU\u002FmL), hepatitis C (HCV antibody-positive with HCV RNA above the lower limit of detection), or co-infection with HBV and HCV; 7.Within 6 months prior to randomization: myocardial infarction, severe\u002Funstable angina, NYHA Class ≥II heart failure, ≥Grade 2 persistent arrhythmia (per NCI CTCAE v5.0), atrial fibrillation of any grade, coronary\u002Fperipheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident (including transient ischemic attack), or symptomatic pulmonary embolism; 8.Severe active infection within 4 weeks prior to randomization (requiring intravenous antibiotics, antifungals, or antivirals) or unexplained fever \\>38.5°C during screening\u002Fbefore first dose; 9.Known allergy to any component of the study drugs; 10.Current participation in another interventional drug clinical study; 11.Pregnancy or lactation; 12.Refusal to comply with follow-up; 13.Other severe physical\u002Fmental illnesses or laboratory abnormalities that may increase study risk, interfere with results, or render the patient unsuitable per investigator judgment.","FEMALE","18 Years","75 Years",{"count":97,"type":98},158,"ESTIMATED","INTERVENTIONAL",[101],"PHASE2","Exploring the dynamics of ctDNA following neoadjuvant therapy with CDK4\u002F6 inhibitors combined with endocrine treatment, and its potential to guide de-escalation of adjuvant chemotherapy",[104,105,106,107,108],"Hormone Receptor-Positive Breast Cancer","High-risk Breast Cancer","Early-Stage Breast Cancer","HER2-negative Breast Cancer","ctDNA Monitoring","2026-07-10",{"date":111,"type":112},"2026-07-13","ACTUAL",{"date":114,"type":112},"2026-04-20",{"date":116,"type":98},"2029-12-31",{"name":5,"class":6},1]