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

基本信息

批准号：
9336547
负责人：
EDWARD CHU
金额：
$ 34.74万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-15 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9336547
关键词：
Address Antineoplastic Agents Assessment tool 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 Evaluation Fatigue Formulation Heavy Metals Herbal Medicine Human Incidence Malignant Neoplasms Mus Myelosuppression National Cancer Institute Natural Products Nausea and Vomiting PHY 906 Patients Personal Satisfaction Pharmaceutical Preparations 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 Treatment-related toxicity Xenograft Model arm base cancer therapy chemotherapy clinical efficacy cytotoxicity design experience health related quality of life human disease improved in vivo inhibitor/antagonist irinotecan novel palliation patient subsets pharmacodynamic biomarker placebo controlled study pre-clinical prospective response

项目摘要

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是一种传统中草药，在东方已有近2000年的历史，用于治疗腹泻和恶心/呕吐。我们的研究小组开发了一种新型的 PHY906 cGMP 配方，已被证明不含重金属和任何其他污染物。我们已经表征了 PHY906 作为抗癌药物细胞毒性调节剂和化疗细胞保护剂的临床前活性。使用小鼠异种移植模型进行的一系列广泛的临床前体内研究表明，这种草药可以增强多种抗癌药物（包括拓扑 I 抑制剂伊立替康）的抗肿瘤活性，并降低毒性。 PHY906联合IFL化疗一线治疗晚期CRC患者的初始l/lla期临床研究初步结果表明，PHY906能够有效降低腹泻、恶心/呕吐以及整体疲劳的胃肠道毒性。这些观察结果表明 PHY906 可以降低与伊立替康为基础的化疗相关的毒性。然而，这项初步试点研究无法确定 PHY906 对伊立替康化疗临床疗效的潜在影响。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（如果不能改善）与该抗癌药物相关的临床活性。为了直接解决这一假设，我们计划进行一项随机、双盲、安慰剂对照的 II 期临床试验，以研究中草药 PHY906 对伊立替康单药治疗的毒性、生活质量和临床疗效的影响二线治疗中的晚期 CRC 患者。患者将被随机分配接受伊立替康加安慰剂的对照组或伊立替康加 PHY906 的实验组。作为本临床研究的一部分，提出了 3 个具体目标：目标 1 将确定 PHY906 对伊立替康单药治疗安全性的影响，重点关注胃肠道毒性，如腹泻和恶心/呕吐，以及骨髓抑制和疲劳。目标 2 将使用成熟且经过验证的患者报告评估工具来研究 PHY906 对伊立替康单药治疗相关整体生活质量的影响。目标 3 将研究 PHY906 对伊立替康单药治疗在总体缓解率、无进展生存期和总生存期方面的临床疗效的影响。