A Dose-Finding Study of Paclitaxel Oral Solution in Neoadjuvant Therapy for Patients With HER2-Positive Breast Cancer
This is a multicenter, open-label, dose-finding trial using a backfill Bayesian optimal interval (BF-BOIN) design to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) for paclitaxel oral solution combined with anti-HER2 treatment. Eligible HER2-positive breast cancer patients receive 6 cycles of neoadjuvant THP regimen(paclitaxel oral solution + trastuzumab+pertuzumab) and are enrolled in three cohorts at oral paclitaxel dose levels 1-3 (125, 150, 175 mg/m²).
• Female, aged 18 to 70 years.
• Histologically confirmed invasive breast cancer by core needle biopsy; clinical stage T1c-4, N0-3, M0 per the AJCC 8th edition breast cancer staging system (T1cN0M0 excluded).
• HER2-positive status defined as IHC 3+ or IHC 2+ with FISH amplification.
• Left ventricular ejection fraction (LVEF) ≥ 50%.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function assessed within 14 days prior to first dose of study drug, without blood transfusion or growth-factor support, meeting the following:
‣ Hematology: absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; platelet count (PLT) ≥ 100 × 10⁹/L; hemoglobin (Hb) ≥ 90 g/L.
⁃ Blood chemistry: total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN; blood urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × ULN; creatinine clearance (CrCl) ≥ 50 mL/min by the Cockcroft-Gault formula.
• Voluntary participation with signed informed consent, good compliance, and willingness to attend follow-up.