anlotinib and niraparib dual therapy evaluation in platinum-resistant recurrent ovarian cancer

Conditions: Platinum-resistant Ovarian Cancer

Summary: at present, the standard treatment for platinum-resistant ovarian cancer patients is platinum-free chemotherapy, with poor efficacy and tolerance. the combination of anti-angiogenic drugs and parpi can play a synergistic anti-tumor role and achieve good efficacy in platinum-sensitive recurrent ovarian cancer. this study intends to explore the safety and effectiveness of anlotinib and niraparib dual therapy in patients with platinum-resistant recurrent ovarian cancer, fallopian tube cancer, and primary peritoneal cancer (ovarian cancer).

the present study is an open, single-center, prospective, single-arm phase ii study to investigate the efficacy and safety of nilapalil combined with anrotidine in the treatment of platinum-resistant recurrent ovarian cancer. in this study, 40 histopathologically diagnosed patients with high-grade serous ovarian, fallopian tube and primary peritoneal cancer were treated with neelapalil plus anrotinib in patients who underwent first-line chemotherapy or above and had a recurrence of platinum-resistant chemotherapy (the time of tumor progression of the last platinum-containing chemotherapy \< 6 months). the study will be divided into two phases. the first phase will include six patients on a 21-day cycle (nierapalil 200mg qd\*21; anrotidine 12mg qd d1-14, d15-21 suspension), all subsequent patients were enrolled if no more than dose-restricted toxic event occurred within a cycle, and the combination treatment was continued until the disease progressed or the toxicity was intolerable.

Eligibility criteria:
inclusion criteria: * 1. subjects understand the trial process, sign informed consent, agree to participate in the study, and have the ability to follow the protocol; 2. 18 \~ 70 years old (inclusive), female; 3. histologically diagnosed ovarian, fallopian tube, or primary peritoneal cancer; 4. subjects were initially treated with platinum, and the disease recurrence occurred within 6 months after the end of the previous platinum-containing chemotherapy, that is, platinum resistance relapsed; 5. life expectancy \> 16 weeks; 6. patient's ecog physical status score is 0-1; 7. subject agrees to take blood samples for gbrca mutations; 8. can provide formalin-fixed, paraffin-embedded tumor tissue samples for sbrca and homologous recombination repair-related genes detection (optional); 9. good organ function, including: * neutrophil count \>= 1500 / μl; * platelets \>= 100,000 / μl; * hemoglobin \>= 9g / dl; * serum creatinine \ = 60ml / min (calculated according to cockcroft-gault formula); * total bilirubin \<= 1.5 times the upper limit of normal value or direct bilirubin \<= 1.0 times the upper limit of normal value; * ast and alt \<= 2.5 times the upper limit of normal value. when liver metastases are present, it must be \<= 5 times the upper limit of normal value. 10. the toxic side effects of any previous chemotherapy have recovered to \<= ctcae level 1 or baseline levels, except for sensory neuropathy or hair loss with stable symptoms \<= ctcae level 2. exclusion criteria: 1. people who are known to be allergic to niraparib or anlotinib (or active or inactive ingredients of drugs with similar chemical structure); 2. symptomatic, uncontrolled brain or pia mater metastases; 3. underwent major surgery within 3 weeks before the study began or has not recovered after surgery; 4. received palliative radiotherapy of \> 20% bone marrow 1 week before enrollment; 5. have invasive cancer other than ovarian cancer (except fully treated basal or squamous cell skin cancer) within 2 years before enrollment; 6. patients with central lung squamous cell carcinoma or at risk for large hemoptysis; 7. previous or currently diagnosed myelodysplastic syndrome (mds) or acute myeloid leukemia (aml); 8. severe or uncontrolled diseases, including but not limited to: uncontrollable nausea and vomiting, inability to swallow or gastrointestinal diseases that may interfere with drug absorption and metabolism; active viral infections; mental illnesses that affect patients' signed informed consent history of bleeding tendency and thrombosis; history of severe cardiovascular disease; 9. laboratory abnormalities: hyponatremia; hypokalemia; uncontrollable nail function abnormalities; 10. receive platelet or red blood cell transfusions within 4 weeks; 11. patients who are pregnant or nursing, or who plan to become pregnant during study treatment; 12. have previously received any parp inhibitor treatment.