Apatinib Combined With Abraxane and Carboplatin or Cisplatinum as First-line Treatment for Epithelial Ovarian Cancer

Inclusion Criteria:

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1.Age 18 - 75 years; 2.Histologically confirmed, stage II or IV epithelial ovarian carcinoma; 3.For Group1,patients with stage III-IV ovarian cancer who are considered unlikely to achieve satisfactory tumor reduction after preoperative evaluation by gynecological oncologists or not suitable for direct surgery are required; 4.Patients with at least one evaluable or measurable lesions as per RECIST version 1.1(CT scan length and diameter of tumor lesion≥10mm CT scan of lymph node lesion was short diameter≥15mm,scan slice thickness 5mm); 5.ECOG performance status (PS) 0 - 2; 6.Life expectancy of at least 12 weeks; 7.Patients with adequate organ function at the time of enrollment as defined below:

1. Blood routine examination standard:(without blood transfusion within 14 days before enrollment)

   1. Hb ≥ 100g/L，
   2. WBC ≥ 3.0×109/L
   3. ANC ≥ 1.5×109/L，
   4. PLT ≥ 100×109/L；
2. Biochemical examination shall meet the following standards:

   1. BIL ≤ 1.5 times the upper limit of normal(ULN);
   2. ALT and AST ≤ 3 ×upper limit of normal(ULN);
   3. Serum creatinine Cr ≤ 1ULN;
   4. Serum creatinine ALB ≥ 30g/L. 8.Women of childbearing age in the serum or urine pregnancy test is negative within 7 days prior to study enrollment and must be Non-lactating patients,and agree to use contraceptives (such as intrauterine devices, contraceptives or condoms) during the study period and within 8 months after the end of the study; males should agree to patients who must use contraception during the study period and within 8 months after the end of the study period.

      9.Subjects voluntarily joined the study, signed informed consent, good compliance, and followed up;

      Exclusion Criteria:
      1. Women who are pregnant or breastfeedind;
      2. Except for other malignant tumors, basal cell carcinoma of the skin and cervical cancer in situ in the past 5 years;
      3. Patients with symptomatic brain metastasis;Significant neurological or psychiatric disorders;
      4. Patients who have participated in other clinical trials in recent three months;
      5. Prior treatment with apatinib or other anti-vascular drugs and other small molecule tyrosine kinase inhibitors;
      6. Patients who have undergone systemic chemotherapy, radiotherapy, surgery, hormone therapy, or immunotherapy before enrollment;
      7. Within 3 months before treatment, there were esophageal (gastric fundus) varicose bleeding, intestinal obstruction and gastrointestinal perforation;
      8. Patients had clinically demonstrated cancerous ascites or pleural effusion;
      9. Patients has active infection or unexplained fever ≥38.5℃ within 7 days before enrollment;
      10. Severe liver, kidney, heart, lung, brain and other major organ failure;
      11. Patients with hypertension that is difficult to control (systolic blood pressure ≥140 mmHg and diastolic blood pressure ≥90 mmHg) despite treatment with several hypotensive agents;
      12. Previous or current had idiopathic pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radioactive pneumonia, histopathological pneumonia (e.g., bronchitis, obliterans), drug-induced pneumonia, or screening stage CT with active pneumonia;
      13. Patients with abnormal coagulation function (INR \> 1.5 or prothrombin time (PT) \> ULN+4 seconds), bleeding tendency or receiving thrombolytic or anticoagulant therapy are allowed to receive low-dose LMWH or oral aspirin to prevent anticoagulant therapy during the trial;
      14. Urine protein ≥ ++ or confirmed 24 hour urine protein quantitation;
      15. Patients with cardiac clinical symptoms or diseases that are not well controlled,such as:(1) NYHA2 or above heart failure;(2) Unstable angina;(3) Myocardial infarction occurred within 1 year;(4) Clinically significant supraventricular or ventricular arrhythmias require treatment or intervention;(5) QTc \> 470ms;
      16. Inability to swallow pills, malabsorption syndrome, or any condition that affects gastrointestinal absorption;
      17. In the 6 months prior to enrollment, patients had been arteriovenous thrombosis (AVT), such as cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis (DVT) and pulmonary embolism;
      18. Patients with a history of hereditary or acquired bleeding or coagulation disorders.There were clinically significant bleeding symptoms or definite bleeding tendency within 3 months before enrollment, such as gastrointestinal bleeding and hemorrhagic gastric ulcer;
      19. According to the judgment of the researcher, the patients have other factors that may lead to the forced termination of this study, such as other serious diseases (including mental diseases) requiring combined treatment, severe laboratory test abnormalities, accompanied by family or social factors, which will affect the safety of the subjects, or the collection of data.