Clinical trial NCT07019363: CDK4/6 Inhibitors Combined With Standard Adjuvant Endocrine Therapy in High-Risk, HR+/HER2+ Early Breast Cancer Patients
Official title: A Study on the Efficacy and Safety of CDK4/6 Inhibitors Combined With Standard Adjuvant Endocrine Therapy in High-Risk, HR+/HER2+ Early Breast Cancer Patients Who Have Completed Adjuvant Anti-HER2 Targeted Therapy"
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Adjuvant Therapy
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2025-06-13
Enrollment: 1903
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: 5-years Invasive disease free survival
timeFrame: 5 years
Secondary outcomes:
measure: Distant Recurrence-Free Survival (DRFS)
timeFrame: 5 years
measure: Overall Survival (OS)
timeFrame: Approximately 5 years
measure: Safety including adverse events (AEs), severe adverse events (SAEs) and adverse events of special interest (AESI).
timeFrame: Up to approximately 3 years
measure: Patient-Reported Outcome (PRO)
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
Study officials:
affiliation: Fudan University
name: zhimin shao
role: PRINCIPAL_INVESTIGATOR
References: