Anlotinib Combined With Dose-reduced Olaparib in Patients With Platinum-Sensitive Recurrent Ovarian Cancer

Inclusion Criteria: 1. Subjects join the study voluntarily and sign informed consent; 2. Female subjects are older than 18 years; 3. ECOG(Eastern Cooperative Oncology Group) physical status score is 0-1; 4. Life expectancy≥3 months; 5. Histologically confirmed FIGO(International Federation of Gynecology and Obstetrics ) III/IV ovarian cancer, fallopian tube cancer, or primary peritoneal cancer; Participants must have high-grade serous or endometrioid histology; 6. Platinum-sensitive recurrent ovarian cancer patients treated with olaparib as maintenance therapy according to NCCN(National Comprehensive Cancer Network) guideline and then suffered dose reduction due to adverse events. The reduction standard of olaparib following its instructions. Platinum-sensitive recurrent ovarian cancer is defined that patients are response to platinum-based chemotherapy and their platinum-free interval is greater than or equal to 6 months. 7. Subjects have enough organ function: (1) Blood routine(without blood transfusion or hematopoietic stimulating factor within 7 days before screening): a.Hemoglobin(HB)≥90g/L; b.absolute neutrophil count(ANC)≥1.5\*10\^9/L; c.Platelet (PLT)≥80\*10\^9/L; (2) Blood biochemical examination(without blood or albumin transfusion within 7 days before screening): a. ALT( Alanine aminotransferase) and AST(Aspartate aminotransferase)≤2.5 times the upper limit of normal value and ALT (AST≤5 times the upper limit of normal value when liver/bone metastasis); b. total bilirubin≤1.5 times the upper limit of normal value; c.serum creatinine≤1.5 times the upper limit of normal value or creatinine clearance≥60ml/min; (3)Blood coagulation function: a. APTT(activated partial thromboplastin time ), INR(international normalized ratio) and PT≤1.5 times the upper limit of normal value; b.Doppler echocardiographic evaluation: left ventricular ejection fraction(LVEF)≥50%; 8. Women of child-bearing age should have negative results of serum or urine pregnancy test within 7 days before recruited and must not be in lactation. Women are willing to adopt the appropriate methods of contraception during the trial and 6 months after last administration. Exclusion Criteria: 1\. Combined disease/history: 1. Hemoptysis occurred within 3 months before admission (hemoptysis\>50ml per day), or significantly clinical bleeding or definite bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal bleeding or red blood cell positive at the baseline, or suffering from vasculitis, etc; 2. Arteriovenous thrombosis events occurred within 6 months before grouping, such as cerebrovascular accident (including temporary ischemic attack), deep venous thrombosis (except venous thrombosis caused by venous catheterization due to prior chemotherapy) and pulmonary embolism, etc; 3. Uncontrolled hypertension by antihypertensive drugs (systolic blood pressure\>140 mmHg or diastolic blood pressure\>90 mmHg); Myocardial infarction, severe/unstable angina pectoris, cardiac insufficiency above NYHA(New York Heart Association) 2, supraventricular or ventricular arrhythmias with clinical significance, and symptomatic congestive heart failure occurred within 6 months before grouping; 4. Interstitial lung disease, non-infectious pneumonia or uncontrollable systemic diseases (e.g. diabetes, pulmonary fibrosis and acute pneumonia); 5. Renal insufficiency: urine routine indicates urinary protein≥++, or confirms 24-hour urinary protein≥1.0g; 6. History of live attenuated vaccine vaccination within 28 days before the first study medication or expected live attenuated vaccination during the study period; 7. HIV infection or known AIDS; active hepatitis (hepatitis B, defined as HBV-DNA≥500 IU/ml; hepatitis C, defined as HCV-RNA higher than the lower limit of detection by analytical method) or co-infection of hepatitis B and hepatitis C; 8. There were severe infections within 4 weeks before the first administration, including, but not limited to, bacteremia and severe pneumonia requiring hospitalization; active infections requiring systemic antibiotics treatment of grade CTCAE≥2 within 2 weeks before the first administration, or unexplained fever\>38.5°C during the screening period/before the first administration (the researchers judged that fever caused by tumors could be included in the group); there was evidence of active tuberculosis infection within 1 year before administration; 9. Any other malignant tumor has been diagnosed within 3 years before enrollment, except for fully treated basal cell carcinoma or squamous cell skin cancer or cervical carcinoma in situ; 10. Major surgery was performed within 28 days before enrollment (tissue biopsy required for diagnosis and central venous catheterization via peripheral venipuncture was allowed); 11. Subjects who have previously received or are prepared to receive allogeneic bone marrow transplantation or solid organ transplantation; 12. Patients with peripheral neuropathy≥Grade 2; patients with active brain metastasis, carcinomatous meningitis, spinal cord compression, or diseases found in brain or leptomeninges by CT or MRI examination during screening (patients with brain metastasis who had completed treatment 14 days before admission and whose symptoms were stable can be enrolled in the group, but they should not suffer symptoms of cerebral hemorrhage confirmed by cranial MRI, CT or venography); (13）Factors that significantly affect the absorption of oral drugs, such as inability to swallow, chronic diarrhea, and intestinal obstruction with clinical significance; 2. Patients who are pregnant or lactation, or who plan to be pregnancy during study; 3. Other serious physical/mental disorders or laboratory abnormalities that may increase the risk of the study or interfere with the results of the study.