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: 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
• 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

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是一种传统的中草药，在东方已经使用了近2000年来治疗腹泻和恶心/呕吐。我们的研究小组已经开发出一种新的PHY906的cGMP配方，该配方已被证明不含重金属和任何其他污染物。我们将PHY906的临床前活性定性为抗癌药物细胞毒性的调节剂和化疗的细胞保护剂。使用小鼠异种移植模型进行的一系列临床前体内研究表明，这种草药可以增强包括Topo I抑制剂伊立替康在内的多种抗癌药物的抗肿瘤活性，并降低毒性。用PHY906联合IFL化疗一线治疗晚期结直肠癌患者的初期L/11a临床研究的初步结果表明，PHY906能够有效地减少腹泻、恶心/呕吐以及全身疲劳的Gl毒性。这些观察表明，PHY906可以减少以伊立替康为基础的化疗的毒性。然而，这项初步的初步研究无法确定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，并保持(如果不是改善)与这种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，以调查中草药PHY906对伊立替康单一疗法治疗二线治疗晚期结直肠癌患者的毒性、生活质量和临床疗效的影响。患者将随机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。作为这项临床研究的一部分，提出了3个具体目标：目标1将确定PHY906对伊立替康单一疗法安全性的影响，重点是G1毒性，表现为腹泻和恶心/呕吐，以及骨髓抑制和疲劳。目的2将使用公认和有效的患者报告评估工具，调查PHY906对伊立替康单一疗法相关的总体生活质量的影响。目的3研究PHY906对伊立替康单一治疗的总有效率、无进展生存期和总生存期的影响。