A Multi-center, Double-blind, Randomized Phase III Clinical Trial of Chiauranib Plus Weekly Paclitaxel in Patients With Platinum-refractory or Platinum-resistant Recurrent Ovarian Cancer

CAR301

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.

2021-12-20

2024-12-31

2025-07-31

Recruiting

Early phase I

376

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.

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2023-08-31