CDK4/6 Inhibitors Combined With Standard Adjuvant Endocrine Therapy in High-Risk, HR+/HER2+ Early Breast Cancer Patients

NCT ID: NCT07019363

Last Updated: 2025-06-13

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1903 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-15
• Study Completion Date: 2033-04-15

Brief Summary

This study is a prospective, open-label, multicenter, randomized controlled Phase III clinical trial. Building upon anti-HER2 targeted therapy combined with endocrine therapy, the addition of CDK4/6 inhibitors has demonstrated greater clinical benefits for advanced TPBC patients. This study aims to investigate the efficacy and safety of CDK4/6 inhibitor combination with standard adjuvant endocrine therapy in HR+/HER2+ early breast cancer patients.

Conditions

Breast Cancer; Adjuvant Therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control

endocrine therapy

Group Type: ACTIVE_COMPARATOR

Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane)

Intervention Type: DRUG

Standard endocrine therapy

Experimental

Standard endocrine therapy combined with CDK4/6i

Group Type: EXPERIMENTAL

Standard endocrine therapy combined with CDK4/6 Inhibitor

Intervention Type: DRUG

CDK4/6 inhibitor therapy for 2 years in combination with standard endocrine therapy

Interventions

Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane)

Standard endocrine therapy

Intervention Type: DRUG

Standard endocrine therapy combined with CDK4/6 Inhibitor

CDK4/6 inhibitor therapy for 2 years in combination with standard endocrine therapy

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Females aged ≥18 and ≤70 years.

2. ECOG systemic status grade 0 to 1.

3. Histologically confirmed invasive HR+/HER2+ breast cancer (Specific definition: breast cancer patients whose estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) are all determined to be positive by pathologic testing. Specifically: ER positive: IHC>10%, PR positive: IHC>10%, HER2 positive: IHC+++ or IHC++ but amplified by FISH.

4. Early-stage breast cancer after radical mastectomy with postoperative pathology consistent with TNM staging of ≥pN2or pN1 with G3 or ≥5cm; or postoperative pathology suggestive of non-pCR after neoadjuvant therapy; or postoperative pathology suggestive of pCR after neoadjuvant therapy but with clinical staging consistent with cT4 or N3 before neoadjuvant therapy

5. Within 1 year of completion of adjuvant anti-HER2 targeted therapy: anti-HER2 targeted therapy includes trastuzumab-based therapy, and/or T-DM1 therapy, and/or TKI therapy.

6. The function of major organs is basically normal, and the following conditions are met: ① The criteria for routine blood tests need to be met: HB ≥ 90g/L (no blood transfusion within 14 days); ANC ≥ 1.5 × 109/L; PLT ≥ 75 × 109/L; ② The biochemical tests need to be met as follows: TBIL ≤ 1.5 × ULN (the upper limit of normal value); ALT and AST ≤ 3 × ULN; serum Cr ≤ 1 × ULN, and endogenous creatinine clearance > 50 ml/min (Cockcroft-Gault formula).

7. Female subjects of childbearing potential are required to use a medically approved form of contraception during study treatment, and for at least 3 months after the last dose of study drug.

8. Subjects voluntarily enrolled in the study, signed an informed consent form, were compliant, and cooperated with follow-up visits.

Exclusion Criteria

1. Bilateral breast cancer;

2. Metastasis to any site;

3. Taking food or medications that are strong inhibitors or inducers of CYP3/4.

1. Strong inhibitors of CYP3/4 include: boceprevir, clarithromycin, konifactam, delavirdine, indinavir, itraconazole, ketoconazole, ritonavir, mibefradil, miconazole, fazodone, nelfinavir, propoxiconazole, ritonavir, saquinavir, naloxone, telaprevir, telithromycin, voriconazole, grapefruit, grapefruit juice, or grapefruit containing foods.

2. Strong inducers of CYP3/4 including carbamazepine, phenytoin, pramipexole, rifampin, and St. John's wort.

4. History of clinically significant or uncontrolled cardiac disease including congestive heart failure, angina pectoris, myocardial infarction within the last 6 months, or ventricular arrhythmia;

5. other malignancy within the previous 5 years, excluding cured carcinoma in situ of the cervix, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin;

6. Pregnant or lactating women, women of childbearing age who are unable to use effective contraception;

7. Patients who are concurrently enrolled in other clinical trials;

8. severe or uncontrolled infection;

9. Patients with known active HBV or HCV infection or Hepatitis B DNA ≥500, or chronic stage with abnormal liver function;

10. Those with a history of psychotropic substance abuse that cannot be stopped or those with psychiatric disorders;

11. Patients who, in the judgment of the investigator, are not suitable for participation in this study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Zhimin Shao

Director of General Surgery of Fudan Shanghai Cancer Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

zhimin shao

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Central Contacts

Zhimin Shao, MD, PhD

Role: CONTACT

zhi_ming_shao@163.com

+86-021-64175590

min he

Role: CONTACT

zhi_ming_shao@163.com

Other Identifiers

SCHBCC-N091

Identifier Type: -

Identifier Source: org_study_id