An Open-label, Randomized Controlled, Multicenter Study With Dual HRD-positive/Negative Cohorts Evaluating Fluzoparib Monotherapy Versus Combination Therapy With Bevacizumab or Dietary Intervention as Maintenance Treatment Following First-line Platinum-based Chemotherapy in Advanced Ovarian Cancer
Fluzoparib has been approved for the first-line maintenance treatment of advanced ovarian cancer in the full population . Previous studies have demonstrated that anti-angiogenic agents enhance tumor cell sensitivity to PARP inhibitors . In vitro evidence suggests that low-carbohydrate culture conditions may restore PARP inhibitor sensitivity in HRD-negative tumor cells. This study aims to validate the survival benefits of fluzoparib combined with bevacizumab in HRD-positive ovarian cancer patients during first-line maintenance therapy and explore the efficacy of fluzoparib combined with a dietary intervention in HRD-negative populations.
• The participant voluntarily joins the study, provides written informed consent, demonstrates good compliance, and agrees to follow-up.
• Female, age ≥18 years (calculated on the day of signing the informed consent form).
• Histologically confirmed high-grade serous ovarian cancer, fallopian tube cancer, or primary peritoneal cancer ; endometrioid adenocarcinoma of the ovary (grade ≥II) :
• For mixed tumors: The high-grade serous or grade ≥II endometrioid component must exceed 50% .
• FIGO 2018 staging as Stage III or IV .
• Documented HRD (Homologous Recombination Deficiency) test results .
• Completed platinum-based chemotherapy with the following requirements:
‣ Patients unable to tolerate chemotherapy for definitive reasons must complete at least 4 cycles of platinum-based chemotherapy .
⁃ Patients undergoing interval debulking surgery must complete at least 3 cycles of platinum-based chemotherapy post-surgery .
• Prior to randomization, patients must have no evidence of disease (NED) or achieve complete response (CR) or partial response (PR) after first-line platinum-based chemotherapy, with response maintained until study treatment initiation. Randomization and treatment must begin within 8 weeks after the last chemotherapy dose .
⁃ CR definition : No radiologic evidence of disease and CA125 ≤ upper limit of normal (ULN).
⁃ PR definition : ≥30% reduction in tumor size compared to pre-chemotherapy or CA125 reduction ≥90% from baseline (if imaging shows no lesions but CA125 remains above ULN).
⁃ For patients achieving NED after initial debulking surgery:CA125 must decrease to \<1×ULN during treatment and remain \<1×ULN within 7 days prior to randomization; or CA125 reduction ≥90% from baseline and no \>10% increase within 7 days prior to randomization.
⁃ Prohibited during/after platinum-based chemotherapy : Concurrent use of other investigational drugs (except endocrine therapy) or treatments.
⁃ Permitted during chemotherapy : Bevacizumab combination therapy.
• ECOG Performance Status (PS) : 0-1.
• Adequate organ function (no blood transfusions or growth factors within 14 days prior to randomization):
⁃ Absolute neutrophil count (ANC) ≥1.5×10⁹/L.
⁃ Platelets ≥90×10⁹/L.
⁃ Hemoglobin ≥9 g/dL.
⁃ Serum albumin ≥3 g/dL.
⁃ Total bilirubin ≤1.5×ULN.
⁃ ALT and AST ≤2.5×ULN.
⁃ Serum creatinine ≤1.5×ULN.
‣ 1 0.For women of childbearing potential :
⁃ Negative serum pregnancy test within 72 hours prior to randomization.
⁃ Agreement to use medically approved contraception during treatment and for 6 months after the last dose .
⁃ Non-lactating.
• Additional Inclusion Criteria for HRD-Negative Cohort Only :
∙ 11\. Baseline body mass index (BMI) ≥18.5 kg/m² (BMI = weight \[kg\]/height \[m\]²).