CLINICAL TRIAL: DEXAMETHASONE-SPARING STUDY COMPARING (HERF) TO PLACEBO

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 200例患者随机分配至两个治疗组之一，将参加这项双盲、安慰剂对照、为期12周的研究。患者随机化将通过（1）原发性或转移性肿瘤，（2）基线时的开放标签地塞米松剂量（4-<8 mg/天、8-16 mg/天或17-24 mg/天）和（3）Karnofsky表现量表（50-70或80-100）分层。 在为期12周的研究的前两周内，将尝试将地塞米松日剂量减少50%。将维持50%的降低直至第5周，之后可根据研究者的判断尝试进一步降低。主要终点是每个治疗组中第2周时为应答者且第5周时仍为应答者的患者比例。应答者定义为表现出以下情况的研究患者：（a）地塞米松剂量相对于基线减少50%或更多;（B）总体10项神经学检查评分与基线相比不变或更低;（c）Karnofsky体能评分与基线相比不变或增加。所有因任何原因（包括数据元素缺失、患者脱落或未能实现地塞米松减少50%而神经功能未恶化（通过10项神经系统检查评分和Karnofsky体能评分测量））不符合应答者定义的患者将被评分为非应答者。将在试验过程中评价第5周后地塞米松的进一步减量、总体安全性和类固醇相关副作用。次要疗效终点包括以下内容：每个治疗组中第2周达到地塞米松使用相对于基线减少50%且神经功能未恶化的患者百分比;每个治疗组中第2周时为应答者且第5周和第8周时继续为应答者的患者比例。此外，将检查信号症状、FACT-Br生活质量模块结果、肌病评估结果较基线的变化。 从基线至研究治疗第5周，神经系统检查必须由同一检查者进行。将尽一切努力确保第5周后由同一名研究者进行神经系统检查。将在第16周进行随访访视。 对于在第2周时地塞米松剂量未减少50%的患者，必须与医学监查员讨论继续逐渐减量的尝试。提前停用设盲研究药物的患者将在停药时接受提前停用研究药物访视。所有患者将在第16周接受最终随访访视。对于在第10周前停用研究药物的患者，将在提前停用研究药物后4周进行额外的计划外随访。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Two hundred patients, randomized to one of two treatment groups, will participate in this double blind, placebo-controlled, 12-week study. Patient randomization will be stratified by (1) primary or metastatic tumor, (2) open-label dexamethasone dose at Baseline (4-<8 mg/day, 8-16 mg/day or 17-24 mg/day) and (3) Karnofsky Performance Scale (50-70 or 80-100). Attempts will be made to reduce daily dexamethasone dose by 50% during the first two weeks of the 12-week study. The 50% reduction is to be maintained until Week 5, after which further reductions may be attempted at the discretion of the Investigator. The primary endpoint is the proportion of patients in each treatment group who are Responders at Week 2 and who continue to be Responders at Week 5. Responders are defined as study patients who demonstrate the following: (a) 50% or greater reduction in dexamethasone dose relative to Baseline; (b) overall 10-Item Neurological Examination Score unchanged or lower compared to Baseline (c) Karnofsky Performance Score unchanged or increased compared to Baseline. All patients not fulfilling the definition of Responder for any reason, including missing data elements, patient drop out, or failure to achieve a 50% reduction in dexamethasone without deterioration in neurological function as measured by the 10- Item Neurological Examination Score and the Karnofsky Performance Score will be scored as non-responders. Further dexamethasone reductions after Week 5, overall safety and steroid associated side effects will be evaluated over the course of the trial. Secondary efficacy endpoints include the following: percent of patients in each treatment group achieving 50% reduction in dexamethasone usage relative to Baseline by Week 2 without deterioration in neurological function; the proportion of patients in each treatment group who are Responders at Week 2 and who continue to be Responders at Weeks 5 and 8. In addition, change from Baseline will be examined for the signal symptom, FACT-Br quality of life module results; myopathy assessment results. From Baseline through Week 5 of study treatment, it is mandatory that the Neurological Examinations be conducted by the same examiner. All efforts will be made to assure that the same investigator perform the Neurological Examinations after Week 5. A Follow-up visit will occur at Week 16. For patients who do not reach a 50% dexamethasone dose reduction by Week 2, continued tapering attempts must be discussed with the Medical Monitor. Patients who discontinue blinded study drug early will be seen for an Early Study Drug Discontinuation visit at time of discontinuation. All patients will have a final Follow-up visit at Week 16. For patients who discontinue study drug prior to Week 10, an additional Unscheduled Follow-up will occur 4 weeks after early study drug discontinuation.