Symptoms and General Pathology

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Edema

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Astrocytoma

Brain Edema

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Nervous System Neoplasms

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Central Nervous System Diseases

Chronic Graft Versus Host Disease

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All Drugs and Chemicals

Dexamethasone

Dexamethasone acetate

BB 1101

Adrenocorticotropic Hormone

Corticotropin-Releasing Hormone

Hormones

Hormone Antagonists

Patients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.

Patient will receive placebo hCRF and any open-label dexamethasone that they are currently taking

hCRF ; open-label dexamethasone that the patient is currently taking

hCRF

placebo hCRF 2mg/day and open-label dexamethasone that they are taking

placebo hCRF

William Shapiro, MD

The purpose of this study is to compare the safety and efficacy of XERECEPT® to dexamethasone (Decadron) a common treatment for symptoms of brain swelling (edema). This study is specifically aimed at patients who require chronic high doses of dexamethasone to manage symptoms.

XERECEPT® is not a potential treatment for cancer, but may reduce the edema associated with tumors and as a result, decrease neurological symptoms.

XERECEPT® (hCRF) for Patients Requiring Dexamethasone to Treat Edema Associated With Brain Tumors

A Phase III Randomized, Double-Blind, Dexamethasone-Sparing Study Comparing Human Corticotropin-Releasing Factor (hCRF) to Placebo for Control of Symptoms Associated With Peritumoral Brain Edema in Patients With Malignant Brain Tumor Who Require Chronic Administration of High-Dose Dexamethasone

The primary efficacy endpoint was the proportion of patients in each treatment group who were Responders at Week 2 and who continued to be Responders at Week 5. Responders were defined as study patients who demonstrated the following:

* 50% or greater reduction in dexamethasone dose relative to Baseline
* Overall 10-Item Neurological Examination Score unchanged or lower compared to Baseline
* Karnofsky Score unchanged or increased relative to Baseline

• The proportion of patients in each treatment group who were Responders at Week 2 and who continued to be Responders at Weeks 5 and 8.

Change from Baseline in the 10-Item Neurological Examination Score at Weeks 2, 5, 8, 12 (or Early Study Drug Discontinuation), and 16 (or 4-week follow-up visit). Each item is scored from 0 (normal) to 4 (severely abnormal) except for speech (0-3) for a total range of 0-39. Total score for each patient was the sum of each item score. Change is calculated as the follow-up score minus the baseline score; a negative value indicates improvement.

Change from Baseline in the Karnofsky Performance Score at Weeks 2, 5, 8, 12 and 16.The Karnofsky score runs from 100 to 0, where 100 is "perfect" health and 0 is death. Although practitioners occasionally assign performance scores in between standard intervals of 10 as follows:

100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of his personal needs.

50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent.

20 - Very sick; hospital admission necessary; active supportive treatment nec

The FACT-Br Quality of Life Questionnaire was self-administered at Baseline, Weeks 5 and 12 (or upon Early SDD), and at the post-treatment 4-week follow-up visit (Week 16 and/or any unscheduled 4-week Follow-up).FACT-Br is a reliable and valid 50-item measure that includes FACT-G (27 items) and a brain subscale (23 items) to assess health-related quality of life in brain tumor patients. Each inventory question is scored from 0 (worst possible QOL) to 4 (best possible QOL)

Myopathy, using Kendall Myopathy Scale, was assessed at Baseline, Week 12 (or upon Early SDD), and at the post-treatment 4-week follow-up visit (Week 16 and/or any unscheduled 4-week Follow-up). The Kendall Myopathy Scale is a 10 point scale where 10 represents holding test position against strong pressure (best) and 0 represents no contraction palpable (worst).

The maximum reduction in dexamethasone usage at any time during the study. Dexamethasone dosage was assessed at Weeks 0, 2, 5, 8, 12 and 16.

Numbers of patients who discontinued prior to the Week 5 assessment

Neurobiological Technologies

Celtic Pharma Development Services

Treatment-emergent adverse events (TEAEs) excluded steroid-related conditions noted on the medical history. One patient was randomized to placebo but was administered hCRF instead. For the assessment of safety, the patient data has been included based on the treatment administered rather than that originally randomized.

Placebo

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Canada

Australia

New Zealand

Region of Enrollment

Patrick O'Connor, MD, Managing Director Clinical Development

The Proportion of Patients in Each Treatment Group Who Are Responders at Week 2 and Continue to be Responders at Week 5

Percent of Patients in Each Treatment Group Achieving 50% Reduction in Dexamethasone Usage Relative to Baseline by Week 2 Without Deterioration in Neurological Function as Measured by the 10-Item Neurological Exam and the KPS

Week 2

Week 5

Week 8

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

Week 12

Last Visit

Change From Baseline in the 10-Item Neurological Examination Score at Weeks 2, 5, 8 12 and 16 (or Early Discontinuation)

Change From Baseline in the Karnofsky Performance Score

Week 16

Change From Baseline in the FACT-Br Quality of Life Results

Change From Baseline in Myopathy Assessment Results at Week 12 (or Early Study Drug Discontinuation) and Week 16 (or 4-week Follow-up Visit)

Intent to Treat population; baseline observation carried forward

Maximum Percent Reduction in Dexamethasone Usage Relative to Baseline Achieved During the Study

Number of Patients Who Discontinued Study Drug Prior to the End of Week 5

Overall Study

Xerecept

This is a phase II, multicenter, open-label, imaging study of hCRF in the reduction of PBE in patients with primary malignant or metastatic brain tumors. Approximately 30 to 60 patients will be assigned to 1 of 3 treatment groups and receive study drug for up to 28 days

The purpose of this study is to investigate the effect of 3 different regimens of subcutaneous (SC) administered hCRF (1.0 mg every \[Q\] 8 hours \[h\], 1.5 mg Q12h, and 1.0 mg Q12h) on the reduction of PBE in patients with primary malignant or metastatic brain tumors as defined by MRI indexes.

Imaging Study of XERECEPT® Treatment for Peritumoral Brain Edema (PBE)

Open-Label, Imaging Study of Human Corticotropin-Releasing Factor (hCRF) for The Reduction of Peritumoral Brain Edema (PBE) in Patients With Primary Malignant or Metastatic Brain Tumors

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
XERECEPT® (hCRF) for Patients Requiring Dexamethasone to Treat Edema Associated With Brain Tumors	NCT00088166	Brain Edema Brain Tumor	hCRF placebo hCRF	18 Years -	Celtic Pharma Development Services
Imaging Study of XERECEPT® Treatment for Peritumoral Brain Edema (PBE)	NCT00691522	Peritumoral Bra... PRIMARY MALIGNA...	Xerecept	18 Years - 65 Years	PharmaNet
XERECEPT® (hCRF) for Patients Requiring Dexamethasone to Treat Edema Associated With Brain Tumors	NCT00088166	Brain Edema Brain Tumor	hCRF placebo hCRF	18 Years -	Celtic Pharma Development Services
Imaging Study of XERECEPT® Treatment for Peritumoral Brain Edema (PBE)	NCT00691522	Peritumoral Bra... PRIMARY MALIGNA...	Xerecept	18 Years - 65 Years	PharmaNet

Spots Global Cancer Trial Database for peritumoral brain edema