Clinical Investigation of the Ceramide NanoLiposome for Advanced Solid Tumors

 描述（由申请人提供）：Keystone Nano与马里兰州大学Greenebaum癌症中心（UMD-GCC）合作，提出对神经酰胺纳米脂质体（CNL）作为一种新型抗癌治疗药物进行多中心临床评价。该项目的总体目标是通过I期临床试验推进CNL。这次审判的结果将 支持肝细胞癌（HCC）预期初始适应症以及其他癌症适应症的后续试验。HCC是全球最常见和最致命的癌症之一，目前无论是批准的还是临床开发中的治疗方法，都不能显著改变诊断为晚期HCC的患者的病程。导致CNL对癌细胞的特异性和选择性毒性的协同作用机制的组合，沿着脂质体递送提供的独特优势，使CNL成为目前HCC疗法的独特和强大的潜在替代方案。许多临床前研究表明，CNL是非常有效的，诱导肝癌模型中的肿瘤消退，而没有全身毒性。CNL的临床前开发组合（包括药代动力学、生物分布、代谢、疗效、安全性和毒理学评价）已发表或作为本申请的附录提供。为了评估CNL的临床效用，由UMD-GCC领导的一组NCI指定的癌症中心与弗吉尼亚大学癌症中心（UVACC）的NCI指定的癌症中心和南卡罗来纳州医科大学（MUSC）的Fred Hollings癌症中心合作，已组成进行拟议的多中心I期临床试验。这项开放标签、剂量递增研究旨在确定CNL的安全性和II期临床试验的推荐参数。具体目的是：1）确定CNL的安全性和最大耐受剂量（MTD），2）量化CNL在人体内的药代动力学（PK）特征，3）检查疾病参数以获得抗癌反应的证据。如果成功，这项研究将推动CNL走向商业化，并实现NIH的使命，将生命系统的基础知识转化为增强健康、减少疾病和延长寿命的应用。

 DESCRIPTION (provided by applicant): Keystone Nano, in partnership with the University of Maryland Greenebaum Cancer Center (UMD-GCC), proposes a multi-site clinical evaluation of the Ceramide NanoLiposome (CNL) as a novel anti-cancer therapeutic. The overall objective of this project is to advance the CNL through a Phase I clinical trial. The results of this trial will support subsequent trials for the intended initial indication of hepatocellular carcinoma (HCC) as well as other cancer indications. HCC is one of the most frequent and deadly cancers worldwide and there are no current treatments, either approved or in clinical development, that substantially alter the course of disease for patients diagnosed with advanced HCC. The combination of synergistic mechanisms of action that result in specific and selective toxicity of the CNL towards cancerous cells, along with the distinct advantages afforded by liposomal delivery, make the CNL a unique and powerful potential alternative to current HCC therapies. Numerous preclinical studies indicate that the CNL is highly efficacious, inducing tumor regression in HCC models without systemic toxicity. The preclinical development portfolio for the CNL including evaluations of pharmacokinetics, biodistribution, metabolism, efficacy, safety and toxicology are either published or provided as Appendices of this application. To evaluate the clinical utility of the CNL, a team of NCI-designated Cancer Centers led by the UMD-GCC, in cooperation with NCI-designated Cancer Centers at the University of Virginia Cancer Center (UVACC) and the Fred Hollings Cancer Center at the Medical University of South Carolina (MUSC), has been assembled to conduct the proposed multi-site Phase I clinical trial. This open-label, dose escalation study is designed to establish the safety of the CNL and recommended parameters for a Phase II clinical trial. Specific Aims are to 1) Establish the safety and maximum tolerated dose (MTD) of the CNL, 2) Quantify the pharmacokinetic (PK) profile of the CNL in humans and 3) Examine disease parameters for evidence of anti-cancer response. If successful, this research will advance the CNL towards commercialization and realize the mission of the NIH to translate fundamental knowledge of living systems into applications that enhance health, reduce illness and lengthen life.