A Randomized, Open-Label, Multi-Cohort Study of Fluzoparib Monotherapy or in Combination With Bevacizumab as Neoadjuvant Therapy in Patients With Advanced Ovarian Cancer
This study is a randomized, open-label, multi-cohort, multicenter clinical trial, aimed at evaluating the efficacy and safety of Fluzoparib monotherapy, Fluzoparib in combination with Bevacizumab, and standard chemotherapy (Paclitaxel plus Carboplatin) as neoadjuvant treatments in newly diagnosed, germline BRCA1/2-mutated epithelial ovarian cancer patients (FIGO stage III/IV). The study also aims to assess the efficacy and safety of Fluzoparib as maintenance therapy following surgery and chemotherapy. The primary endpoint of the study is the objective response rate (ORR) for neoadjuvant therapy, as assessed by the investigator using RECIST v1.1 criteria. Secondary endpoints include R0 resection rate, overall survival (OS), and progression-free survival (PFS). The study will also evaluate the safety, tolerability, and patient-reported outcomes (EQ-5D-5L) across the three treatment cohorts.
• The subject voluntarily agrees to participate and signs the informed consent form.
• Age ≥18 years (calculated as of the date of signing the informed consent).
• Pathologically diagnosed with newly diagnosed, FIGO stage III-IV high-grade (or moderate/low-grade) serous ovarian cancer, fallopian tube cancer, or primary peritoneal cancer; grade ≥II endometrioid adenocarcinoma of the ovary; Mixed tumors: high-grade serous or ≥II grade endometrioid component must be \>50%.
• The subject has at least one measurable lesion that can be assessed by CT or MRI (RECIST v1.1).
• According to the investigator's assessment, the patient is unable to achieve R0 resection or cannot tolerate surgery.
• a) Criteria for determining inability to achieve R0 resection include: i. Fagotti laparoscopic score ≥8. ii. If laparoscopic assessment is difficult, an upper abdominal Suidan's CT score ≥3.
• b) Criteria for inability to tolerate surgery include: i. Body mass index (BMI) ≥40. ii. Multiple chronic diseases. iii. Malnutrition or hypoalbuminemia. iv. Moderate to large ascites. v. Newly diagnosed venous thromboembolism. vi. ECOG performance status \>2. vii. Other reasons judged by the investigator.
• Expected survival \>12 weeks.
• ECOG performance status: 0-2.
• Confirmed germline BRCA1/2 mutations by professional genetic testing.
• Function of major organs meets the following requirements (no blood products or colony-stimulating factors allowed within 14 days prior to the first dose):
∙ Absolute neutrophil count ≥1.5 × 10\^9/L.
‣ Platelet count ≥100 × 10\^9/L.
‣ Hemoglobin ≥9 g/dL.
‣ Serum albumin ≥3 g/dL.
‣ Bilirubin ≤1.5 times the upper limit of normal (ULN).
‣ ALT and AST ≤2.5 times ULN, must be ≤5 times ULN in the presence of liver metastases.
‣ Serum creatinine ≤1.5 times ULN, or creatinine clearance ≥60 mL/min (calculated using the Cockcroft-Gault formula).
⁃ Female patients of childbearing potential must have a negative blood pregnancy test within one week before the first dose and are not breastfeeding. They must agree to use effective contraception during the study and for 6 months after the last dose of Bevacizumab/Fluzoparib/chemotherapy. Pregnancy, if confirmed, must be terminated as soon as possible.
⁃ The subject is willing to cooperate in completing quality of life surveys during the treatment and follow-up periods and agrees to have the survey results used for clinical research.