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

Sponsor
Peking University People's Hospital
Study ID
NCT06970912
Phase
PHASE2
Status
Recruiting
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Conditions

  • Breast Cancer Early Stage Breast Cancer (Stage 1-3)
  • Early-Stage Breast Cancer
  • HER2-negative Breast Cancer
  • High-risk Breast Cancer
  • Hormone Receptor-Positive Breast Cancer
  • ctDNA Monitoring

Eligibility Criteria

Sex
FEMALE
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Dalpiciclib + Aromatase Inhibitor with ctDNA-Guided Therapy — DRUG
    Patients receive 4 cycles of neoadjuvant dalpiciclib (125 mg orally, days 1-21 of 28-day cycles) combined with an aromatase inhibitor (letrozole/anastrozole/exemestane). Post-surgery treatment is guided by ctDNA status: （1）ctDNA-negative at baseline and post-neoadjuvant, with post-op Ki67 ≤10% :Continue dalpiciclib + endocrine therapy (ET) for 2 years； （2）ctDNA-positive → negative, or persistently ctDNA-negative with post-op Ki67 \>10% :Randomized 1:1 to: * Arm B1: Dalpiciclib + ET for 2 years. * Arm B2: Adjuvant chemotherapy (investigator's choice) → dalpiciclib + ET for 2 years；（3）Persistently ctDNA-positive or ctDNA-negative → positive: Mandatory adjuvant chemotherapy → dalpiciclib + ET for 2 years. Premenopausal women undergo ovarian suppression with LHRH agonists.
  • Taxane-Based Neoadjuvant Chemotherapy — DRUG
    Patients receive 4 cycles of taxane-based neoadjuvant chemotherapy (e.g., paclitaxel 80 mg/m² weekly or docetaxel 75-100 mg/m² triweekly) before surgery. Post-surgery adjuvant chemotherapy (physician's choice) may be administered. This arm serves as the control group for comparing standard chemotherapy efficacy.

Study Details

* 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 Dates

First listed
May 14, 2025
Start date
Aug 1, 2025
Status verified
Jan 2026
Primary completion
Dec 31, 2029
Completion
Dec 31, 2029

Study Design

Enrollment
393 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Taxane Neoadjuvant Chemo ± Adjuvant Therapy
    Arm Description: This group receives neoadjuvant taxane-based chemotherapy (e.g., paclitaxel 80 mg/m² weekly or docetaxel 75-100 mg/m² triweekly for 4 cycles) before surgery. Post-surgery adjuvant chemotherapy (whether or not and how to adopt depend on the physician's choice) may be administered ± CDK4/6 inhibitors. The intervention aims to compare standard chemotherapy efficacy as a control. Intervention phases: * Neoadjuvant: Chemotherapy only * Adjuvant: Optional chemotherapy based on physician discretion ± （CDK4/6 inhibitors+endocrine therapy） Key endpoints: Pathological response 0/1 (RCB 0/1), safety profiles.
  • Experimental: Dalpiciclib + AI with ctDNA-Driven Adjuvant
    Arm Description: Patients receive 4 cycles of neoadjuvant dalpiciclib (125 mg/day, 21 days on/7-off) combined with aromatase inhibitors (letrozole/anastrozole/exemestane). Post-surgery treatment is guided by ctDNA status: 1. ctDNA-negative at baseline and post-neoadjuvant, with post-op Ki67 ≤10% ：Continue dalpiciclib + endocrine therapy (ET) for 2 years. 2. ctDNA-positive → negative, or persistently ctDNA-negative with post-op Ki67 \>10% : Randomized 1:1 to: * Arm B1: Dalpiciclib + ET for 2 years. * Arm B2: Adjuvant chemotherapy (investigator's choice) → dalpiciclib + ET for 2 years. 3. Persistently ctDNA-positive or ctDNA-negative → positive: Adjuvant chemotherapy → dalpiciclib + ET for 2 years. Premenopausal women receive ovarian suppression with LHRH agonists.

Primary Outcome Measure

ctDNA Clearance Rate after Neoadjuvant Therapy [ Time Frame: From baseline to 4 weeks post-neoadjuvant therapy (pre-surgery) ]

Central Contacts

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