[Translation] A prospective, randomized, positive parallel controlled, double-blind, double-dummy multicenter study of icariin soft capsules versus cinobufacin tablets in first-line therapy with complex disease, poor prognosis, compound biomarker-positive, unresectable hepatocellular carcinoma at baseline Phase III clinical trial
主要目的:
比较淫羊藿素组与华蟾素组受试人群的总生存期(OS)。
次要目的:
比较两组受试人群的9/12/18个月OS率、疾病进展时间(TTP)、无进展生存期(PFS)、客观缓解率(ORR)和疾病控制率(DCR);
比较两组受试人群的至生活质量恶化时间(TTD),包括健康相关生活质量/总体健康状况(HRQoL/GHS)、躯体功能、角色功能和症状;
比较两组受试人群的安全性与耐受性;
进行群体药代动力学(PopPK)探索研究,评估淫羊藿素给药后的药代动力学(PK)特征及其影响因素,并探索暴露与疗效的关系。
探索性目的:
在蛋白水平和基因组(DNA、RNA)水平上探索外周血生物标志物与临床疗效的相关性,支持受试者的伴随诊断以及精准治疗;
PopPK研究中探索受试者基因组学信息,包括代谢酶尿苷二磷酸葡萄糖基转移酶(UGTs)的基因型,多药耐药相关蛋白2(MRP2)、多药耐药1(MDR1)、乳腺癌耐药蛋白(BCRP)、有机阴离子转运体3(OAT3)等转运体的基因型与PK特征的相关性;以及药物暴露水平与疗效的相关性。
[Translation] main purpose:
The overall survival (OS) of the subjects in the icariin group and the cinobufagin group was compared.
Secondary purpose:
The 9/12/18-month OS rate, time to disease progression (TTP), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were compared between the two groups of subjects;
The time to quality of life deterioration (TTD), including health-related quality of life/general health status (HRQoL/GHS), physical function, role function and symptoms, were compared between the two groups of subjects;
Compare the safety and tolerability of the two groups of subjects;
A population pharmacokinetic (PopPK) exploratory study was conducted to evaluate the pharmacokinetic (PK) characteristics and influencing factors of icariin after administration, and to explore the relationship between exposure and efficacy.
Exploratory Purpose:
Explore the correlation between peripheral blood biomarkers and clinical efficacy at the protein level and genome (DNA, RNA) level, and support the companion diagnosis and precision treatment of subjects;
Genomic information was explored in the PopPK study, including the genotypes of the metabolizing enzymes uridine diphosphate glucosyltransferases (UGTs), multidrug resistance-related protein 2 (MRP2), multidrug resistance 1 (MDR1), breast Correlation between genotypes of transporters such as cancer resistance protein (BCRP) and organic anion transporter 3 (OAT3) and PK characteristics; and the correlation between drug exposure levels and efficacy.