PERITUMORAL BRAIN EDEMA IN PATIENTS WITH PRIMARY MALIGNANT GLIOMA; (HCRF) TO DEX

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所在的机构。 本研究的目的是检查与地塞米松相比，人促肾上腺皮质激素释放因子（hCRF）在需要增加地塞米松剂量以控制瘤周脑水肿症状的原发性恶性胶质瘤患者中的安全性和有效性。 主要疗效终点将比较应答者，即每个治疗组中在第1周结束时显示改善并在第2周结束时验证应答的患者比例。 改善定义为： a）10项神经学检查的总评分较低， 相对于基线至少25%，和 B）Karnofsky表现评分相对不变或增加 至基线，以及 c）基线后地塞米松剂量没有增加超过 1天，最大允许增加量小于4 mg， 那天 次要终点将评价第2周后缓解的持久性、至治疗失败的时间、每个治疗组中地塞米松使用的检查以及通过信号神经症状评分、Karnofsky体能评分、10项神经检查评分和FACT-Br生活质量模块结果测量的神经/临床状态。将在8周试验过程中评价hCRF的总体安全性和类固醇毒性。 120例患者随机分为两组，将参加这项为期8周的双盲、阳性对照研究。患者将按照（1）多形性胶质母细胞瘤（GBM）与非GBM肿瘤（2）基线时的地塞米松剂量（0、1 - 8和9 - 24 mg/d）和（3）10项神经学检查评分（3 - 4、5 - 8、8）分层。在研究治疗期间，必须在基线、第1周和第2周进行患者神经系统评估。 将在第12周进行最终4周随访。在末次随访访视时，患者可入组hCRF的开放标签、扩展使用研究（NTI 0501）。 扩展使用研究是GCRC方案#909。

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. The objective of this study is to examine the safety and efficacy of human corticotropin-releasing factor (hCRF) compared to dexamethasone in patients with primary malignant glioma who require increased dexamethasone doses to control symptoms of peritumoral brain edema. The primary efficacy endpoint will compare responders, i.e. the proportion of patients in each treatment group who show improvement at the end of Wk 1 and verify that response at the end of Week 2. Improvement is defined as: a) a lower overall score on the 10-Item Neurological Examination of at least 25%, relative to Baseline, and b) a Karnofsky Performance score unchanged or increased relative to Baseline, and c) No post-Baseline increase in dexamethasone dose on more than 1 day, with a maximum allowable increase of less than 4 mg on that day. The Secondary endpoints will evaluate the durability of response beyond Week 2, time to therapeutic failure, examination of dexamethasone use in each treatment group and neurological/clinical status as measured by the Signal Neurological Symptom Score, Karnofsky Performance Score, 10-Item Neurological Exam Score and the FACT-Br quality of life module results. Overall safety of hCRF and steroid toxicities will be evaluated over the course of the 8-week trial. 120 patients, randomized into two arms, will participate in this double-blind, positive-controlled, 8-week study. Patients will be stratified by (1) Glioblastoma multiforme (GBM) versus non-GBM tumors (2) dexamethasone dose at Baseline (0, 1-8 and 9-24 mg/d) and (3) 10-Item Neurological Exam Score (3-4, 5- 8, 8). During study treatment, it is mandatory that patient neurological assessments be made at Baseline, Week 1 and Week 2. A final 4-week follow-up will occur at Wk 12. At the final follow-up visit, patients may enroll in an open-label, extended-use study of hCRF (NTI 0501.) The extended-use study is GCRC protocol #909.