Clinical Study of PHY906, a Novel Chinese Herbal Medicine, as a Modulator of Irin

新中药PHY906作为艾琳调节剂的临床研究

• 批准号: 8555270
• 负责人: EDWARD CHU
• 金额: $ 51.14万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8555270
• 关键词: Address; Antineoplastic Agents; Biological Factors; Biological Markers; Body Weight decreased; Chemotherapy-Oncologic Procedure; Chinese Herbs; Clinical; Clinical Research; Common Terminology Criteria for Adverse Events; Cyclic GMP; Cytoprotective Agent; Development; Diarrhea; Dose; Double-Blind Method; Drug Formulations; Evaluation; Fatigue; Heavy Metals; Herbal Medicine; Human; Incidence; Malignant Neoplasms; Mus; Myelosuppression; National Cancer Institute; Nausea and Vomiting; PHY 906; Patients; Personal Satisfaction; Pharmaceutical Preparations; Pharmacodynamics; Phase; Phase II Clinical Trials; Physical Function; Pilot Projects; Placebo Control; Placebos; Progression-Free Survivals; Quality of life; Randomized; Refractory; Reporting; Research; Safety; Series; Symptoms; Toxic effect; Xenograft Model; arm; base; cancer therapy; chemotherapy; clinical efficacy; cytotoxicity; design; experience; health related quality of life; human TOP1 protein; human disease; improved; in vivo; inhibitor/antagonist; irinotecan; novel; palliation; placebo controlled study; pre-clinical; prospective; response; tool

PHY906 is a traditional Chinese herbal medicine that has been used in the Orient for nearly 2000 years to treat diarrhea and nausea/vomiting. Our research group has developed a novel cGMP formulation of PHY906 that has been shown to be free of heavy metals and any other contaminants. We have characterized the preclinical activity of PHY906 as a modulator of cytotoxicity of anticancer agents and a cytoprotective agent of chemotherapy. An extensive series of pre-clinical in vivo studies using mouse xenograft models have shown that this herbal medicine can enhance the antitumor activity of a broad range of anticancer agents, including the topo I inhibitor irinotecan, and reduce toxicity. Preliminary results from an initial phase l/lla clinical study with PHY906 in combination with IFL chemotherapy in the front-line treatment of advanced CRC patients showed that PHY906 was able to effectively reduce the Gl toxicities of diarrhea and nausea/vomiting as well as overall fatigue. These observations suggested that PHY906 can reduce the toxicities associated with irinotecan-based chemotherapy. However, this initial pilot study was unable to determine the potential effect of PHY906 on the clinical efficacy of irinotecan chemotherapy. Our hypothesis is that PHY906 will be able to enhance the safety profile associated with irinotecan chemotherapy and maintain, if not improve, the clinical activity associated with this anticancer agent. To directly address this hypothesis, we plan to conduct a randomized, double-blind, placebo-controlled phase II clinical trial to investigate the effects ofthe Chinese herbal medicine PHY906 on the toxicity, quality of life, and clinical efficacy of irinotecan monotherapy in the treatment of patients with advanced CRC in the second-line setting. Patients will be randomized to receive the control arm of irinotecan plus placebo or to the experimental arm of irinotecan plus PHY906. As part of this clinical study, 3 specific aims are proposed: Aim 1 will determine the effect of PHY906 on the safety profile of irinotecan monotherapy with a focus on Gl toxicity, in the form of diarrhea and nausea/vomiting, as well as myelosuppression and fatigue. Aim 2 will investigate the effect of PHY906 on overall quality of life associated with irinotecan monotherapy using well-established and validated patient-reported assessment tools. Aim 3 will investigate the effect of PHY906 on the clinical efficacy of irinotecan monotherapy with respect to overall response rates, progression-free survival, and overall survival.

PHY906是一种传统的中草医学，在东方使用了将近2000年的时间来治疗腹泻和恶心/呕吐。我们的研究小组开发了一种新型的PHY906的CGMP公式，该公式已证明不含重金属和任何其他污染物。我们已经将PHY906的临床前活性描述为抗癌剂的细胞毒性调节剂和化学疗法的细胞保护剂。使用小鼠异种移植模型的一系列广泛的临床前体内研究表明，这种草药可以增强广泛的抗癌剂的抗肿瘤活性，包括拓扑I抑制剂Irinotecan，并降低毒性。初始阶段L/LLA临床研究的初步结果与PHY906结合了晚期CRC患者的前线治疗中的IFL化学疗法，表明PHY906能够有效地降低腹泻和恶心/呕吐的GL毒性以及整体疲劳。这些观察结果表明，PHY906可以降低与基于虹膜的化学疗法有关的毒性。但是，这项初步的试点研究无法确定PHY906对伊立替康化疗的临床功效的潜在影响。我们的假设是，PHY906将能够增强与伊立替康化疗相关的安全性，并维持（如果不改善）与该抗癌剂相关的临床活性。为了直接解决这一假设，我们计划进行一项随机，双盲，安慰剂控制的II期临床试验，以研究中草药PHY906对伊立替康综合疗法对二线CRC患者治疗的毒性，生活质量和临床功效的毒性，生活质量和临床功效。患者将被随机接收Irinotecan Plus安慰剂的对照组或Irinotecan Plus Phy906的实验组。作为这项临床研究的一部分，提出了3个具体目的：AIM 1将确定Phy906对Irinotecan单一疗法的安全性，重点是GL毒性，以腹泻和恶心/呕吐以及骨髓抑制和疲劳的形式。 AIM 2将研究PHY906对使用良好和经过验证的患者报告的评估工具的PHY906对与Irinotecan单一疗法相关的整体生活质量的影响。 AIM 3将研究PHY906对伊立替康单一疗法对总体反应率，无进展生存和总体生存的临床疗效的影响。