chiauranib plus weekly paclitaxel in patients with platinum-refractory or platinum-resistant recurrent ovarian cancer

Conditions: Ovarian Cancer; Relapsed or Refractory; Chiauranib; Paclitaxel

Summary: this randomized, double-blind, 2-arm study will evaluate the efficacy and safety of chiauranib plus weekly paclitaxel versus placebo plus weekly paclitaxel in patients with platinum-refractory or platinum-resistant recurrent ovarian cancer.

chiauranib is a novel orally active multi-target inhibitor that simultaneously inhibits the angiogenesis-related kinases (vegfr2, vegfr1, vegfr3, pdgfra and c-kit), mitosis-related kinase aurora b and chronic inflammationrelated kinase csf-1r in a high potency manner with the ic50 at a single-digit nanomolar range. in particular, chiauranib showed very high selectivity in the kinase inhibition profile with little activity on off-target non-receptor kinases, proteins, gpcr and ion channels, indicative of a better drug safety profile in terms of clinical relevance. patients will be randomized to receive treatment with either paclitaxel + chiauranib or paclitaxel + placebo. paclitaxel will be repeated every 21 days for a maximum of 6 cycles. patients with objective response/stable disease after completing 6 courses of chemotherapy will continue chiauranib or placebo until progression.

Eligibility criteria:
inclusion criteria: * willingness to sign a written informed consent document . * female, age ≥18 yrs and ≤70 yrs. * histological or cytological confirmation of epithelial ovarian cancer, carcinoma tube, or primary peritoneal carcinoma. * patients with platinum refractory or platinum resistant ovarian cancer: * platinum refractory: progression during the first platinum-based treatment or within 4 weeks after the first platinum-based primary therapy; * platinum resistant: progression during the platinum-based treatment except for platinum refractory, or within 6 months after the last receipt of platinum-based treatment (patients have received platinum containing chemotherapy at least 4 weeks); * radiological progression during the last treatment administered; * no more than 1 prior treatment regimens for recurrent disease. * eastern cooperative oncology group (ecog) performance status of 0 or 1. * at least 1 lesion can be accurately measured, as defined by recist1.1. * laboratory criteria are as follows: * complete blood count: hemoglobin (hb) ≥90g/l ; absolute neutrophil count (anc) ≥1.5×109/l ; platelets ≥90×109/l; * biochemistry test: serum creatinine(cr) \<1.5×uln; total bilirubin\<1.5×uln; alanine aminotransferase(alt) ,aspartate aminotransferase(ast)≤2.5×uln; (alt,ast≦5×uln if liver involved) ; * coagulation test: international normalized ratio (inr) \< 1.5, activeated partial thromboplasting time (aptt) \<1.5×uln * life expectancy of at least 3 months. exclusion criteria: * patients received vascular endothelial growth factor(vegf)/vascular endothelial growth factor receptor(vegfr) inhibitor, like apatinib, anlotinib, fruquintinib, bevacizumab, etc., or aurora kinase inhibitors. * patients received weekly paclitaxel therapy. * has known allegies to chiauranib, paclitaxel or any of the excipients. * biological therapy, immunotherapy, hormonal therapy within 28 days prior to the first dose of study drug. * prior major surgery or trauma within 14 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer. * treatment with an investigational agent/instrument within 28 days prior to first dose of study drug. * any ongoing toxicity from prior anti-cancer therapy that is \>grade 1. * patients with prior invasive malignancies in the past five years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ. * history or clinical evidence of central nervous system (cns) metastases or leptomeningeal carcinomatosis. * clinically significant central/peripheral nervous system disease. * have uncontrolled or significant cardiovascular disease, including: * congestive heart failure, unstable angina pectoris, myocardial infarction within 6 months prior to study entry; arrhythmia, or left ventricular ejection fraction (lvef) \< 50% requiring treatment with agents during screening stage. * primary cardiomyopathy(dilated cardiomyopathy, hypertrophic cardiomyocyte, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, et,al) * history of significant qt interval prolongation, or corrected qt interval (qtc) \> 470 ms prior to study entry * symptomatic coronary heart disease requiring treatment with agents * history of hypertension treated by≥2 agents, or the blood pressure (bp) ≥140/90 mmhg prior to study entry. * other condition investigator considered inappropriate * significant intravenous or arterial thrombosis, such as cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (dvt) within the past 6 months. * history of active bleeding within the past 2 months, patients with bleeding potential during the screening period, or receiving anticoagulation therapy. * ct or mri of the chest during the screening period shows interstitial lung disease or pulmonary fibrosis or lung inflammation that requires treatment, or within 6 months before the first dose, history of pneumonia requiring oral or intravenous steroid treatment, history of immune-associated pneumonia after treatment of pd1/pdl1 inhibitor. * have clinical significant gastrointestinal abnormality that would impair the ingestion, transportation or absorption of oral agents, history of gastrointestinal perforation or abdominal fistula, peptic ulcer disease within 6 months prior to first dose of study drug or gi obstruction within the past 3 months. * pleural fluid, ascites or pericardial effusion with significant symptoms or required treatment of puncture or drainage during the screening period, or history of drainage for therapy within 1 months prior to first dose of study drug. * screening for hiv antibody positive. * screening test for hepatitis b surface antigen (hbsag) or hepatitis b core antibody (hbcab) positive with virus replication, hepatitis c antibody (hcv-ab) positive with virus replication. * active infection requiring oral or intravenous systemic antimicrobial therapy during the screening period. * any mental or cognitive disorder, that would impair the ability to understand the informed consent document, or the compliance of study. * history of organ transplantation or allo-hsct. * any mental or cognitive disorder, that would impair the ability to understand the informed consent document, or the compliance of study. * candidates with drug and alcohol abuse. * participants of reproductive potential not willing to use adequate contraceptive measures for the duration of the study.pregnant or breastfeeding women. * any other condition which is inappropriate for the study in the opinion of the investigators.