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Hormone Receptor-Positive Breast CancerPhase 2DNACDKHRNCT07366112

CDK4/6 Inhibitors Combined With Endocrine Therapy for Neoadjuvant Treatment

A Phase 2 study testing CDK4/6 inhibitor with endocrine therapy in people with Hormone Receptor-Positive Breast Cancer and High-risk Breast Cancer, run by Peking University People's Hospital at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Exploring the dynamics of ctDNA following neoadjuvant therapy with CDK4/6 inhibitors combined with endocrine treatment, and its potential to guide de-escalation of adjuvant chemotherapy Read more about this study

Who is it for?
Ages 18 to 75 years, women only
What is being tested?
CDK4/6 inhibitor with endocrine therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
158 participants
Where
1 siteChina
Study dates
20 Apr 2026to 31 Dec 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 1.Female breast cancer patients aged ≥18 years and ≤75 years, either postmenopausal or premenopausal/perimenopausal; 2.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); 3. 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;
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  • 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:
  • <!-- -->
  • 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.

Who cannot join

  • 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/mL), 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/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; 8.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; 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/mental illnesses or laboratory abnormalities that may increase study risk, interfere with results, or render the patient unsuitable per investigator judgment.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

yuan peng, doctor contact

86+13671287670

13671287670@163.com

China1 site, 1 recruiting
  • Peking University People's Hospital

    Beijing, Beijing Municipality, 100044

    yuan peng, Doctor, 86+13671287670, 13671287670@163.com

    Recruiting

Other trials in China

About this study

Official title: CDK4/6 Inhibitors Combined With Endocrine Therapy for Neoadjuvant Treatment of Breast Cancer: ctDNA-Guided Personalized Therapy

Exploring the dynamics of ctDNA following neoadjuvant therapy with CDK4/6 inhibitors combined with endocrine treatment, and its potential to guide de-escalation of adjuvant chemotherapy

Read the detailed description

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+/HER2- 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.

Preclinical 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. CDK4/6 inhibitors, such as Dalpiciclib, have revolutionized advanced HR+/HER2- 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.

Study Objectives Primary Objectives: Assess ctDNA clearance rate (defined as conversion from detectable to undetectable ctDNA) after 4 cycles of neoadjuvant CDK4/6i + endocrine therapy.

Secondary Objectives Evaluate 3-year event-free survival (EFS), where events include local/distant recurrence, secondary malignancies, or death.

Compare safety profiles of CDK4/6i + endocrine therapy versus chemotherapy.

Evaluate tumor response metrics:

Pathological 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.

Exploratory Objectives Correlate ctDNA clearance with long-term outcomes (e.g., EFS, overall survival).

Study Design

All patients received 4 cycles of neoadjuvant CDK4/6i + endocrine therapy. Post-Surgery Treatment: ctDNA-negative post-neoadjuvant: Continue CDK4/6i + endocrine therapy ctDNA-positive post-neoadjuvant: Optional adjuvant chemotherapy followed by CDK4/6i + endocrine therapy.

Being tested
CDK4/6 inhibitor with endocrine therapy
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CDK4/6 inhibitor with endocrine therapyDrug

    CDK4/6 inhibitor with endocrine therapy for neoadjuvent therapy

Study groups in NCT07366112
Study groupRoleWhat they receive
CDK4/6 inhibitor with endocrine therapyExperimentalPatients receive 4 cycles of neoadjuvant CDK4/6 inhibitor with endocrine therapy. Post-surgery treatment is guided by ctDNA status: ctDNA-negative at baseline and post-neoadjuvant, with post-op Ki67 ≤10% :Continue CDK4/6 inhibitor with endocrine therapy for 2-3 years. ctDNA-positive → negative, or persistently ctDNA-negative with post-op Ki67 >10% : Randomized 1:1 to: Arm 1: CDK4/6 inhibitor with endocrine therapy for 2-3 years. Arm 2: Adjuvant chemotherapy (investigator's choice) → CDK4/6 inhibitor with endocrine therapy for 2-3 years. (3)Persistently ctDNA-positive or ctDNA-negative → positive: Adjuvant chemotherapy → CDK4/6 inhibitor with endocrine therapy for 2-3 years. Premenopausal women receive ovarian suppression with LHRH agonists.
Receives: Drug: CDK4/6 inhibitor with endocrine therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. ctDNA Clearance Rate after Neoadjuvant Therapy

    Proportion of patients achieving conversion from detectable to undetectable ctDNA in plasma after 4 cycles of neoadjuvant CDK4/6i+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.

    Measured: From baseline to 4 weeks post-neoadjuvant therapy (pre-surgery)

Secondary outcomes (5)
  1. 3-Year Event-Free Survival (EFS)

    Time from randomization to first occurrence of locoregional/distant recurrence, contralateral breast cancer, secondary malignancy, or death from any cause. Assessed via imaging (CT/MRI), pathology, and clinical exams every 3 months for 3 years. Events are adjudicated by blinded independent review committee.

    Measured: From neoadjuvant therapy to 36 months post-surgery

  2. 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.

    Measured: At surgery (approximately 16 weeks since neoadjuvant therapy)

  3. Objective Response Rate (ORR) by RECIST 1.1

    Proportion of patients with complete/partial response per RECIST 1.1 criteria during neoadjuvant phase, measured by MRI/CT. Target lesion size reduction ≥30% (partial) or disappearance (complete) required, confirmed by two consecutive assessments ≥4 weeks apart.

    Measured: Baseline to pre-surgery (week 16)

  4. 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).

    Measured: Post-neoadjuvant therapy (pre-surgery, week 16)

  5. 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/AST elevation), and cardiac (LVEF decline ≥10%) toxicities. Events are monitored every cycle during neoadjuvant therapy and quarterly during adjuvant phase.

    Measured: From first dose to 30 days after last treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jan 2026
  2. Study start20 Apr 2026
  3. Primary completion1 Jan 2028 (estimated)
  4. Study completion31 Dec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
All patients receives oral CDK4/6 inhibitor combined with endocrine therapy.
Masking
None (open label)
Enrolment
158 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07366112
Sponsor's protocol ID
PKUPH2025CDK46NAE
Acronym
DNACDKHR
Status last verified
Feb 2026
First submitted
18 Jan 2026
Last updated
13 Jul 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CDK4/6 inhibitor with endocrine therapy in people with Hormone Receptor-Positive Breast Cancer and High-risk Breast Cancer, run by Peking University People's Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 13 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact yuan peng, doctor (86+13671287670, 13671287670@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ctDNA Clearance Rate after Neoadjuvant Therapy (time frame: From baseline to 4 weeks post-neoadjuvant therapy (pre-surgery)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2026.

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