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

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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.