A Single-arm, Open-label Study of Fluzoparib Combination With Chemotherapy for Neoadjuvant Treatment of HRD-positive, HR+/HER2- Breast Cancer
The purpose of this clinical trial is to evaluate the efficacy and safety of Fluzoparib combined with docetaxel in sequential paclitaxel combined with cyclophosphamide for HRD-positive, HR+/HER2- early breast cancer. The main question it aims to answer is: Does the proportion of patients with residual tumor burden (RCB) 0/I increase when Fluzoparib combined with docetaxel is sequentially followed by paclitaxel combined with cyclophosphamide for patients with HRD-positive, HR+/HER2- early breast cancer? What medical problems will participants encounter when using Fluzoparib combined with docetaxel in sequential paclitaxel combined with cyclophosphamide? Participants will: After confirming their enrollment, they need to receive the trial drug treatment within 72 hours, with each 3-week period as a treatment cycle, for a total of 8 cycles. The first to fourth cycles will receive Fluzoparib combined with docetaxel treatment, and the fifth to eighth cycles will receive paclitaxel and cyclophosphamide treatment. The treatment will continue until the end of the treatment course or disease progression, occurrence of intolerable toxicity, or the subject withdrawing the informed consent form.
• Subjects must meet all of the following inclusion criteria to be enrolled in this trial:
⁃ Female patients with newly diagnosed breast cancer, aged ≥18 years and ≤70 years;
⁃ Histopathologically confirmed early or locally advanced HR+/HER2- invasive breast cancer, as defined by the latest ASCO/CAP guidelines, meeting the following conditions:
∙ HER2-negative: IHC 0/1+ or IHC 2+ with negative ISH;
‣ ER-positive: IHC \>1%; PR-positive: IHC \>1%;
‣ cT1c or above with positive lymph nodes; cT2 or above with negative lymph nodes must meet at least one of the following: age ≤40 years; Ki67 \>50%; lymphovascular invasion; histological grade III;
‣ HRD-positive: defined as HRD score ≥42 points and/or germline BRCA1/2 mutation (pathogenic or likely pathogenic);
‣ ECOG performance status 0-1;
⁃ Presence of at least one measurable lesion according to RECIST 1.1 criteria;
⁃ Organ function must meet the following requirements:
• 1\) Hematology
• Absolute neutrophil count (ANC) ≥1.5×109/L (no use of hematopoietic stimulating factors within 14 days before the first administration of the study drug);
• Platelet count (PLT) ≥100×109/L (no blood transfusion within 14 days before the first administration of the study drug);
• Hemoglobin (Hb) ≥90 g/L; 2) Blood biochemistry
• Total bilirubin (TBIL) ≤1.5×ULN;
• Aspartate transaminase and alanine transaminase (ALT and AST) ≤2.5×ULN;
• Blood urea nitrogen (BUN) and creatinine (Cr) ≤1.5×ULN; 3) Cardiac function
• Echocardiogram: LVEF ≥50%;
• 12-lead electrocardiogram: QTc interval \<470 ms in females. 5. Subjects voluntarily participate in the study and sign the informed consent form.