螺旋藻肽聚糖复合物胶囊对比肝复乐胶囊一线治疗晚期肝细胞癌的前瞻性、随机、双盲对照、全国多中心的Ⅱ期临床研究报告

Randomized,multicenter,double-blind,positive controlled,phaseⅡstudy of Spirulina peptidoglycan complex(K-001)in untreated advanced hepatocellular carcinoma

目的探索新药螺旋藻肽聚糖复合物胶囊(K-001)在晚期肝细胞癌(HCC)患者中的安全性和有效性。方法本研究为前瞻性、随机、双盲、阳性对照、全国多中心的Ⅱ期临床研究。自2012年9月至2016年3月,共入组100例晚期HCC患者,随机分为K-001组(试验组)和肝复乐胶囊组(对照组)。采用RECIST 1.1版标准评价客观疗效;NCI CTC 4.0版标准评价不良事件。结果治疗后,试验组和对照组的中位疾病进展时间(TTP)分别为1.48个月和1.41个月(P=0.946),中位总生存时间(OS)分别为5.17个月和4.57个月(P=0.374),差异均无统计学意义。无高危因素亚组分析显示,K-001有延长生存的趋势(7.0个月vs.4.67个月,P=0.447;9.10个月vs.4.67个月,P=0.675)。K-001治疗后血红蛋白、白蛋白、淋巴细胞和嗜酸性粒细胞较对照组显著升高,且以上指标与死亡风险呈负相关;碱性磷酸酶和血小板/淋巴细胞比值(PLR)较对照组显著降低,且与死亡风险呈正相关。“无门脉侵犯”亚组中,K-001组治疗后疼痛轻于对照组(P=0.002)。K-001安全性良好,无与药物肯定或可能相关的严重不良事件发生。结论K-001治疗国人晚期HCC的疗效与肝复乐胶囊相似,分层分析显示,在部分亚组有生存获益的趋势和减轻癌痛的作用;同时,安全性良好,值得在特定人群扩大样本量进一步临床探索。

Objective To investigate the safety and efficacy of Spirulina peptidoglycan complex(K-001)in advanced hepatocellular carcinoma(HCC)patients.Methods The multicencer,randomized,phase II,double blinded,positive controlled clinical study involved 100 patients with untreated local advanced or metastatic HCC in China.They were randomly assigned at a ratio of 1:1 to receive either K-001(n=50)or Ganfule capsule(n=50)treatment.Objective efficacy was evaluated by RECIST 1.1 and adverse events were evaluated by NCI CTC AE 4.0.Results The median time to tumor progress(TTP)in K-001 group and control group were 1.48 months and 1.41 months(P=0.946),median overall survival(OS)were 5.17 months and 4.57 months(P=0.374),respectively.There was no significant difference in the two groups.Patients with no high risk trended to have longer OS(7.0 months vs.4.67 months,P=0.447;9.10 months vs.4.67 months,P=0.675),but no significant difference was observed.The hemoglobin,lymphocyte count,eosinophilic granulocyte count and albumin were significantly higher after K-001 treatment,rather than control group,which were negatively related to death.While the PLR and AKP were significantly lower after K-001 treatment,which were positively related to death.In the non-portal invasion subgroup,the pain of patients in K-001 group was less than that of control group.K-001 had excellent safety,and no definite drug related SAE was observed.Conclusion The effect of K-001 in Chinese advanced HCC patients is similar to Ganfule capsule.K-001 trended to have survival benefit and reducing pain in some subgroups.K-001 shows good safety in this clinical trial,and it is worth further clinical exploration in some specific population.