A Study of Apatinib Combined With Letrozole With or Without Fluzoparib in Estrogen Receptor-Positive, Platinum-Sensitive Recurrent Ovarian Cancer Previously Treated With First-Line PARP Inhibitor

Exclusion Criteria

• •Patients allergic to the trial drug or its excipients;
• •Patients with active brain metastases;
• •Patients who have received systemic treatment with traditional Chinese medicine or immunomodulatory agents (including thymosin, interferon, interleukin, excluding local use for pleural effusion control) within 2 weeks prior to the first dose;
• •Patients with severe cardiovascular diseases: myocardial ischemia or myocardial infarction of grade II or above, uncontrolled arrhythmias (including QTc interval ≥ 470 ms); heart function of grade III-IV (according to the New York Heart Association \[NYHA\] classification), or echocardiogram showing left ventricular ejection fraction (LVEF) \< 50%;
• •Patients with severe infections within 4 weeks prior to the first dose (e.g., requiring intravenous antibiotics, antifungals, or antivirals), or unexplained fever \> 38.5℃ during the screening period or prior to the first dose; or patients who have undergone major surgical procedures within 3 weeks prior to the first dose;
• •Patients with type I diabetes mellitus whose blood glucose is controlled with insulin therapy may be eligible for this study;
• •Patients with human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), untreated active hepatitis B, hepatitis C (positive hepatitis C antibody and HCV-RNA above the lower limit of detection of the assay), or co-infection with hepatitis B and C;
• •Patients who have undergone or are planned to undergo solid organ or hematopoietic stem cell transplantation during the study period (excluding corneal transplantation);
• •Patients currently participating in an interventional clinical study or who have received other investigational drugs or study devices within 4 weeks prior to the first dose; patients who have not fully recovered from toxicities and/or complications caused by any prior interventions (i.e., ≤ grade 1 or returned to baseline, excluding fatigue or alopecia);
• •Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 110 mmHg despite optimal medical therapy);
• •Coagulation abnormalities (INR \> 1.5 or prothrombin time (PT) \> ULN + 4 seconds or APTT \> 1.5 ULN), tendency to bleed, or receiving thrombolytic or anticoagulant therapy;
• •Urinalysis showing proteinuria ≥ ++, or confirmed 24-hour urine protein ≥ 1.0 g;
• •Patients with a history of allergy that may potentially cause hypersensitivity or intolerance to the trial drug or similar biologics;
• •Patients with a history of substance abuse or psychiatric disorders that cannot be discontinued;
• •Patients with a history of hereditary or acquired bleeding disorders or coagulopathies (eligibility to be determined by the investigator);
• •Patients currently receiving strong CYP3A4 inhibitors (e.g., itraconazole, telithromycin, clarithromycin), moderate CYP3A4 inhibitors (e.g., ciprofloxacin, clarithromycin, fluconazole), strong CYP3A4 inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampin), or moderate CYP3A4 inducers (e.g., bosentan, modafinil). A washout period of 5 weeks is required for enzalutamide or phenobarbital, and 3 weeks for other drugs prior to the start of study treatment;
• •Patients who have received small-molecule tyrosine kinase inhibitors (TKIs) for antiangiogenesis after achieving CR/PR with second-line platinum-based chemotherapy and using bevacizumab as maintenance therapy (patients previously treated with bevacizumab are allowed, but those treated with pazopanib, sorafenib, regorafenib, sunitinib, lenvatinib, anlotinib, etc., are not allowed);
• •Patients with a history of cerebrovascular accident or transient ischemic attack within 6 months;
• •Patients with other severe physical or psychiatric diseases or laboratory abnormalities that may increase the risk of participating in the study, interfere with study treatment or study results, or any other conditions deemed by the investigator as unsuitable for participation in this study.