A Phase III, Open-label, Randomized, Controlled Study of Utidelone in Combination With AC Versus Docetaxel in Combination With AC for Neoadjuvant Chemotherapy in Patients With High-risk Early-stage or Locally Advanced HER2-negative Breast Cancer
The purpose of this clinical trial is to evaluate the efficacy and safety of Utidelone plus AC versus Docetaxel plus AC as neoadjuvant chemotherapy in high-risk HER2-negative early-stage or locally advanced breast cancer. In this phase III, multi-center, open-label, randomized controlled study, 552 subjects will be enrolled and randomly assigned in a 1:1 ratio to either the Utidelone plus AC group or the docetaxel plus AC group, stratified by hormone receptor status (ER and/or PgR positive vs ER and PgR negative).
• Female patients who will receive initial treatment, 18 ≤ years of age ≤70.
• Pathologically confirmed HER2-negative breast cancer at each investigational site with IHC at 0 or 1+, or IHC at 2+ with HER2 being negative by ISH (please refer to the ASCO/CAP Guideline 2020 for the relevant definition).
• For patients with triple negative breast cancer, the requirement is tumor size\>2 cm or lymph node-positive (T1, N1-3, M0, T2-4, any N, M0; tumor stage: II or III).
• For patients with HR-positive and HER2-negative breast cancer, the requirement is (T2-4, N1-3, M0 or T2-4, N0 with high risk factors, M0):
‣ Tumor size\>2cm
⁃ lymph node-positive or high-risk factor with pathologically negative lymph node. High risk factors include:
• A. histologic grade 3.
• B. high Ki67 expression (≥20%).
• Baseline routine blood tests within 1 week prior to enrollment is normal, with CTCAE grade ≤1 (based on normal values at each site's laboratory). No rhG-CSF use and no blood transfusion/EPO etc. within 14 days prior to enrollment.
• A. White blood cell count ≥ 4.0× 109/L;
• B. Neutrophil count ≥ 1.5 × 109/L;
• C. Platelet count ≥ 100 × 109/L;
• D. Hemoglobin ≥100 g/L.
• Blood biochemistry test result is normal within 1 week prior to enrollment, with CTCAE grade ≤1 (based on normal values at each site's laboratory).
• A. Total bilirubin ≤ upper limit of normal (ULN).
• B. AST and ALT ≤ 1.5 x ULN.
• C. alkaline phosphatase ≤ 2.5×ULN.
• D. Serum creatinine ≤ 1.5×ULN.
• Left ventricular ejection fraction (LVEF) on cardiac ultrasound ≥55%.
• ECOG performance status 0 or 1.
• Females of childbearing potential must agree to use effective contraception during the study and within 6 months after the last dose. The blood or urine pregnancy test for female patients of childbearing age prior to enrollment must be negative.
⁃ The patient willingly participates in this study, will sign the informed consent form, and commits to following the treatment and follow-up schedule.