Project 3 - Phase I/II Trial of Trametes Versicolor

在亚洲和北美有执照的自然疗法医生都开出了药用蘑菇的提取物(TV)作为乳腺癌女性的辅助免疫疗法。日本的数据表明，电视可能会提高早期乳腺癌的存活率，减少复发。虽然电视是由NDS和其他CAM从业者开出的，并在乳腺癌患者中作为非处方药的补充越来越频繁地使用，但在美国还没有精心设计的临床研究。标准化的商业产品得到了广泛的使用。拟议的口服TV的I/II期临床试验将是这种前景看好的CAM辅助免疫调节癌症疗法在美国的第一次试验。 主要目的：1)对雌激素受体阴性的I期和I1a期乳腺癌患者进行一项观察性研究(n=22)，以监测和量化放射治疗结束后6周内免疫恢复的自然过程和不良事件，以及疲劳和生活质量评分的变化。2)测定口服标准电视胶囊的安全性和耐受性。 斐波那契剂量递增设计(n=24)，剂量从3000 mg/d到12,000 mg/d。I期试验的目标是确定最大耐受量。次要目标：3)收集初步数据，比较基线和治疗后的免疫措施，最多四个TV剂量队列，取决于MTD：3000毫克、6000毫克、9000毫克和12000毫克/天口服封装的标准TV剂量。终点包括白细胞(WBC)、自然杀伤细胞活性、巨噬细胞吞噬指数以及外周血单核细胞产生干扰素-γ和肿瘤坏死因子-α的水平。4)确定测量近期完成化疗和放射治疗的I期或I1a期乳腺癌患者与电视治疗相关的变化和生活质量变化的可行性。乳腺癌患者将从西雅图和明尼阿波利斯两个城市招募。研究对象将在西雅图巴斯蒂尔大学自然健康中心和明尼苏达大学综合医院进行筛选和评估 临床研究中心。每个站点将负责招募和评估每个站点的23名患者。所有临床数据将被发送到位于Bastyr的该中心的临床数据核心，以进行数据输入和分析。这些初步数据将有助于该中心估计电视在乳腺癌患者中的后续随机疗效试验的效果大小。

Extracts of the medical mushroom Trametes versicolor (Tv) are prescribed as adjunctive immune therapy for women with breast cancer in both Asia and by licensed N. American naturopathic physicians. Japanese data suggest that Tv may improve survival and reduce recurrence in early stage breast cancer. While Tv is prescribed by NDs and other CAM practitioners and used with growing frequency among breast cancer patients as an over-the-counter supplement there have yet to be well-designed clinical studies in the U.S. Standardized commercially available products are in wide use. The proposed phase I/II clinical trial of orally administered Tv will be the first U.S. trial of this promising CAM adjunctive immunomodulatory cancer therapy. Primary Aims: 1) To conduct an observational study (n=22) with estrogen receptor negative Stage I and Ila breast cancer patients in order to monitor and quantify the natural course of immune recovery and adverse events, as well as changes in fatigue and QOL scores, during the six weeks immediately following the completion of radiation therapy. 2) To determine the safety and tolerability of orally administered capsules of standardized Tv using a modified Fibonacci dose-escalation design (n=24) with doses ranging from 3000 mg - 12,000 mg/day. The goal of the phase I trial is to determine the maximally tolerated dose. Secondary Aims: 3) To gather preliminary data that compare baseline and post-treatment immunologic measures in up to a maximum of four Tv dose cohorts depending on the MTD: 3000 mg, 6000 mg, 9000 mg, and 12,000 rag/day oral doses of encapsulated standardized Tv. End points include white blood cells (WBC), natural killer cell activity, macrophage phagocytic index, and peripheral blood mononuclear cell production of levels of interferon gamma and turrior necrosis factor-alpha. 4) To determine the feasibility of measuring changes infatigue and quality of life changes associated with Tv administration in women with Stage I or Ila breast cancer who have recently completed chemotherapy and radiation therapy. Breast cancer patients will be recruited from two cities, Seattle and Minneapolis. Study subjects will be screened and evaluated at the Bastyr University's Center for Natural Health in Seattle and the University of Minnesota's General Clinical Research Center. Each site will be responsible for recruiting and evaluating 23 patients each. All clinical data will be sent to the Center's Clinical Data Core located at Bastyr for data entry and analysis. These preliminary data will assist the Center in estimating effect sizes for later randomized efficacy trials of Tv in breast cancer patients.