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

Brain Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00088166
• Other study ID #: NTI 0303
• Secondary ID: XERECEPT®
• Status: Completed
• Phase: Phase 3
• First received: July 20, 2004
• Last updated: July 22, 2014
• Start date: May 2004
• Est. completion date: March 2008

Study information

• Verified date: July 2014
• Source: Celtic Pharma Development Services
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Other known NCT identifiers

• NCT00091013

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: March 2008
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed diagnosis of a primary malignant brain tumor or, if metastatic, documentation and histology (if available) of primary source of cancer.

• Patient must have 1 or more qualifying steroid-associated side effect(s) at Baseline.

• Patient has required administration of dexamethasone to control symptoms of peritumoral edema for at least 30 days.

• Stable dexamethasone dose of 4-24 mg/day for at least 14 days prior to Baseline.

• Need for administration of dexamethasone to treat peritumoral brain edema (referenced above) has been documented by MRI or comparable diagnostic technology within 21 days of Baseline.

• Karnofsky score of > 50 at Screening and Baseline.

• Capable of self-administration of subcutaneous injections twice daily for 12 weeks, or availability of assistance from caregiver.

• Ability to provide written informed consent or, if unable to provide, have a legal guardian or representative provide written informed consent.

• For women of childbearing potential: a negative serum pregnancy test at Screening.

• Must be 18 years of age or older

Exclusion Criteria:

• Ongoing or anticipated need for surgery, radiosurgery or radiation therapy or the introduction of new chemotherapeutic regime within the first 5 weeks of study enrollment. Treatment with pre-study chemotherapy may continue.

• Concurrent enrollment in any other investigational drug or device study, or plan to enroll in such a study during the first 5 weeks of treatment.

• Systemic steroid use for any indication other than peritumoral brain edema.

• Use or intended use of dexamethasone as an anti-emetic during Screening or Study

• Non-compliance with dexamethasone or anticonvulsant therapy.

• Clinical signs and symptoms of cerebral herniation.

• Serious concomitant cardiovascular, pulmonary, renal, gastrointestinal or endocrine metabolic disease which could put the patient at unusual risk for study participation.

• Confounding previous or concurrent neurological disorders that would interfere with adequate clinical evaluation.

• Clinically significant head injury or chronic seizure disorder, if the condition results in functional impairment or is likely to interfere with evaluations. (Maintenance anticonvulsant therapy is allowed.)

• Central nervous system infection.

• Pregnancy, breastfeeding and/or refusal to practice birth control while in study, for women of childbearing potential.

• Any conditions that are considered contraindications for patients to receive niacin, e.g. liver disease (with LFTs > 3 times the upper limit of the norm),active peptic ulcer, arterial hemorrhage, asthma and known hypersensitivity to niacin.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Edema
• Brain Neoplasms
• Brain Tumor
• Edema

Intervention

Drug:
• hCRF
hCRF ; open-label dexamethasone that the patient is currently taking
• placebo hCRF
placebo hCRF 2mg/day and open-label dexamethasone that they are taking

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Queen Elizabeth II Health Sciences Center	Halifax	Nova Scotia
Canada	Kingston General Hospital	Kingston	Ontario
Canada	The Moncton Hospital	Moncton	New Brunswick
Canada	Ottawa Regional Cancer Centre	Ottawa	Ontario
Canada	Sunnybrook and Women's College Health	Toronto	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Dent Neurologic Institute	Amherst	New York
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Northwestern University, Feinberg School of Medicine	Chicago	Illinois
United States	Good Samaritan Hospital	Cincinnati	Ohio
United States	University Hematology Oncology Care, LLC	Cincinnati	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Hermelin Brain Tumor Center, Henry Ford Hospital	Detroit	Michigan
United States	Colorado Neurological Institute	Englewood	Colorado
United States	Evanston Northwestern Healthcare	Evanston	Illinois
United States	UCSF Fresno Center for Clinical Studies	Fresno	California
United States	Mayo Clinic	Jacksonville	Florida
United States	University of Wisconsin	Madison	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Medical College of Cornell University	New York	New York
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Cancer Institute of Orlando	Orlando	Florida
United States	Stanford University Medical Center	Palo Alto	California
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	Oregon Clinic	Portland	Oregon
United States	Neurology Group of Bergen County	Ridgewood	New Jersey
United States	UC Davis Medical Center, Division of Medical Oncology	Sacramento	California
United States	UC San Diego, Thornton Hospital	San Diego	California
United States	Virginia Mason Clinic	Seattle	Washington
United States	Moffitt Cancer Center & Research Institute	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Celtic Pharma Development Services	Neurobiological Technologies

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Proportion of Patients in Each Treatment Group Who Are Responders at Week 2 and Continue to be Responders at Week 5	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	Prospective	No
Secondary	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		Prospective	No
Secondary	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	• 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.	Prospective	No
Secondary	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 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.	Prospective	No
Secondary	Change From Baseline in the Karnofsky Performance Score	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	Prospective	No
Secondary	Change From Baseline in the FACT-Br Quality of Life Results	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)	Prospective	No
Secondary	Change From Baseline in Myopathy Assessment Results at Week 12 (or Early Study Drug Discontinuation) and Week 16 (or 4-week Follow-up Visit)	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).	Prospective	No
Secondary	Maximum Percent Reduction in Dexamethasone Usage Relative to Baseline Achieved During the Study	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.	Prospective	No
Secondary	Number of Patients Who Discontinued Study Drug Prior to the End of Week 5	Numbers of patients who discontinued prior to the Week 5 assessment	Prospective	Yes