Efficacy and Safety of Niraparib Combined With Bevacizumab in Platinum Refractory/Resistant Recurrent Ovarian Cancer

Inclusion Criteria:

1. Subjects understand the trial process, sign informed consent, agree to participate inthe study, and have the ability to follow the protocol;
2. Participant must be female ≥18 years of age;
3. Histologically confirmed FIGO stage III or IV ovarian cancer, fallopian tube cancer,or primary peritoneal cancer;
4. Participants must have high-grade serous or endometrioid histology;
5. Subjects were initially treated with platinum, and the disease recurrence occurredwithin 6 months after the end of the previous platinum-containing chemotherapy, thatis, platinum resistance relapsed; Subjects have disease progression during initialplatinum based chemotherapy defined as platinum refractory;
6. Patients may have received a PARP inhibitor as first-line maintenance therapy;
7. Patients may have received bevacizumab though no other prior use of anti-angiogenictherapy；
8. Subjects must have measurable lesions (according to RECIST1.1) and radiologicallyconfirmed disease progression at the time of previous treatment; or CA125 elevated fortwo consecutive times and 2.5 times upper the limit of normal value；
9. Subject agrees to take blood samples for gBRCA mutations, can provide formalin-fixed,paraffin-embedded tumor tissue samples for sBRCA and homologous recombinationdeficiency(HRD) detection;
10. Life expectancy>12 weeks;
11. Subject's ECOG physical status score is 0-2;
12. Good organ function, including:Neutrophilcount≥1500/μL;Platelets≥100,000/μL;Hemoglobin≥10g/dL;Serum creatinine≤1.5 times theupper limit of normal value, or creatinine clearance≥60mL/min (calculated according toCockcroft-Gault formula);Total bilirubin≤1.5 times the upper limit of normal value ordirect bilirubin≤ 1.0 times the upper limit of normal value;AST and ALT≤2.5 times theupper limit of normal value. When liver metastases are present, it must be≤5 times theupper limit of normal value;
13. For women with fertility potential, if blood test or urine pregnancy test is negativewithin one week before enrollment, effective contraceptive measures must be taken,such as physical barrier contraceptive method (condom) or complete abstinence. Oral,injectable or implantable hormonal contraceptives are not allowed. Or women withoutreproductive potential, defined as: I. Natural menopause and menopause for more than 1year; II. Surgical sterilization (bilateral oophorectomy, bilateral salpingectomy orhysterectomy); III. serum follicle-stimulating hormone, luteinizing hormone, andplasma estradiol levels were within the menopausal criteria of the research centerlaboratory;
14. Subject is able to adhere to the protocol;
15. The adverse effect of any previous chemotherapy have recovered to ≤ Grade1 (CTCAEv5.0) or baseline levels, except for sensory neuropathy or hair loss with stablesymptoms ≤ Grade2 (CTCAE v5.0).

Exclusion Criteria:

1. Personnel involved in the formulation or implementation of the research plan;
2. Patient participated in other clinical trails using other experimental drugs at thesame time as the study;
3. People who are known to be allergic to Niraparib or Bevacizumab (or active or inactiveingredients of drugs with similar chemical structure);
4. People who are inability to swallow oral drugs and any gastrointestinal diseases thatmay interfere with the absorption and metabolism of the study drugs, such asuncontrollable nausea and vomiting, gastrointestinal obstruction or malabsorption;
5. Major surgery was performed within 4 weeks before the start of the study or did notrecover after the operation;
6. Received palliative radiotherapy of >20% bone marrow 1 week before enrollment;
7. The subjects had other malignant diseases in past 2 years, except skin squamous cellcarcinoma, basal-like carcinoma, breast intraductal carcinoma in situ, or cervicalcarcinoma in situ;
8. Previous or currently diagnosed myelodysplastic syndrome (MDS) or acute myeloidleukemia (AML);
9. Patients with serious and uncontrollable diseases or the general situation of thesubjects judged by the researchers to be unsuitable for enrolling the study, includingbut not limited to: active viral infection, such as human immunodeficiency virus,hepatitis B, hepatitis C, etc.; severe cardiovascular disease, uncontrollableventricular arrhythmia, myocardial infarction in the last three months; uncontrollablegrand mal epilepsy, Unstable spinal cord compression, superior vena cava syndrome orother mental disorders that affect patients to sign the informed consent; hypertensionbeyond drug control; immune deficiency (except splenectomy) or other diseases thatresearchers consider may expose patients to high-risk toxicity;
10. The previous history of thromboembolism was defined as: uncontrolled pulmonaryembolism, deep venous thrombosis, and other related conditions after anticoagulanttherapy for more than 3 months before enrollment;
11. Any medical history or existing clinical evidence indicates that there may beconfusion of study results, interference with patients' compliance with the trialprotocol throughout the study treatment period, or not in the best interests ofpatients;
12. Receive platelet or red blood cell transfusions within 4 weeks;
13. Patients who are pregnant or lactation, or who plan to become pregnant during studytreatment.