Fluzoparib+Bevacizumab/Dietary Intervention vs Fluzoparib Monotherapy as First-line Maintenance in HRD+/- Advanced Ovarian Cancer

Korábbi kezelés

• Untreated central nervous system (CNS) metastases :
  • -Patients with stable CNS metastases (confirmed by imaging for ≥1 month) after prior systemic/local therapy (e.g., surgery/radiotherapy) and off steroids (\>10 mg/day prednisone equivalent) for \>2 weeks may be eligible.
• Prior use of PARP inhibitors (e.g., olaparib, niraparib, rucaparib, pamiparib, fluzoparib).
  • 4 .Inability to swallow tablets or gastrointestinal dysfunction affecting drug absorption (per investigator judgment).
  • 5.Bowel obstruction or gastrointestinal perforation within 3 months prior to randomization.
  • 6.Symptomatic malignant ascites/pleural effusion requiring drainage or drainage within 3 months prior to randomization.
  • 7.Poorly controlled cardiac disease :
• Bleeding tendency or current use of thrombolytics/anticoagulants (low-dose LMWH or aspirin prophylaxis permitted).
  • 9.Clinically significant bleeding within 3 months prior to randomization (e.g., gastrointestinal bleeding, hemorrhagic gastric ulcer, vasculitis).
• If baseline fecal occult blood test is positive, retesting is required. Persistent positivity may necessitate endoscopy.
  • 10.Active ulcers, unhealed wounds, or fractures . 11.Uncontrolled hypertension (systolic ≥140 mmHg or diastolic ≥90 mmHg despite medication).
  • 1 2.Grade ≥2 bleeding events (per CTCAE v5.0) within 4 weeks prior to randomization.
  • 13.Active infection or unexplained fever \>38.5°C during screening/prior to randomization.
  • 14.Immunodeficiency or active hepatitis :
• Chemotherapy, radiotherapy, hormonal therapy, or targeted therapy within 4 weeks prior to study treatment (or 5 half-lives for oral targeted agents).
• Residual toxicity from prior therapy \>Grade 1 (CTCAE v5.0; alopecia excluded). 16.Arterial/venous thromboembolism within 6 months prior to randomization (e.g., stroke, transient ischemic attack, DVT, pulmonary embolism).
  • 17.Hereditary/acquired bleeding disorders (e.g., hemophilia, thrombocytopenia).
  • 18.Planned use of other systemic anticancer therapies during the study. 19.Any condition that, per investigator judgment, may lead to premature study termination.
  • Additional Exclusion Criteria for HRD-Negative Cohort Only :
  • 20\. Unintentional weight loss ≥5% within 3-6 months or presence of cachexia .
  • 21\. Nutritional risk :
  • -NRS2002 score ≥3 or need for nutritional support. 22.Diabetes requiring insulin or insulin secretagogues . 23.Acute liver disease/dysfunction . 24.Active chronic or acute kidney disease/dysfunction

Más betegség

• NYHA Class ≥II heart failure.
• Unstable angina.
• Myocardial infarction within 1 year.
• Clinically significant arrhythmias requiring treatment.
• HIV-positive.

Laborértékek

• QTc interval \>470 ms. 8.Coagulation abnormalities :
• INR \>1.5 or PT \>ULN +4 seconds.
• Active HBV (HBsAg+ and HBV DNA ≥500 IU/mL) or HCV (HCV Ab+ and HCV RNA \>ULN).
  • 1 5.Recent anticancer therapy :

Életkor

• History of other untreated or active malignancies within 5 years (except cured thyroid cancer, basal cell carcinoma, cervical carcinoma in situ, or breast cancer with \>3 years of recurrence-free survival after radical surgery).

• 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).