DEXAMETHASONE-SPARING STUDY COMPARING HERF TO PLACEBO

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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. 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 17-24mg/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.