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

Phase 3
Completed
Conditions
Brain Edema
Brain Tumor
Interventions
Registration Number
NCT00088166
Lead Sponsor
Celtic Pharma Development Services
Brief 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.

Detailed Description

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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
200
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
IIplacebo hCRFPatient will receive placebo hCRF and any open-label dexamethasone that they are currently taking
IhCRFPatients will take hCRF (XERECEPT) 2mg/day and open label-dexamethasone they are currently taking.
Primary Outcome Measures
NameTimeMethod
The Proportion of Patients in Each Treatment Group Who Are Responders at Week 2 and Continue to be Responders at Week 5Prospective

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

Secondary Outcome Measures
NameTimeMethod
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 KPSProspective
The Proportion of Patients in Each Treatment Group Who Are Responders at Week 2 and Who Continue to be Responders at Weeks 5 and 8Prospective

• 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 Karnofsky Performance ScoreProspective

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

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

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).

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

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.

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

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 FACT-Br Quality of Life ResultsProspective

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)

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

Numbers of patients who discontinued prior to the Week 5 assessment

Trial Locations

Locations (34)

UC San Diego, Thornton Hospital

🇺🇸

San Diego, California, United States

Northwestern University, Feinberg School of Medicine

🇺🇸

Chicago, Illinois, United States

Colorado Neurological Institute

🇺🇸

Englewood, Colorado, United States

Evanston Northwestern Healthcare

🇺🇸

Evanston, Illinois, United States

Ottawa Regional Cancer Centre

🇨🇦

Ottawa, Ontario, Canada

Beth Israel Deaconess Medical Center

🇺🇸

Boston, Massachusetts, United States

Mayo Clinic

🇺🇸

Jacksonville, Florida, United States

Neurology Group of Bergen County

🇺🇸

Ridgewood, New Jersey, United States

Oregon Clinic

🇺🇸

Portland, Oregon, United States

The Moncton Hospital

🇨🇦

Moncton, New Brunswick, Canada

Sunnybrook and Women's College Health

🇨🇦

Toronto, Ontario, Canada

Queen Elizabeth II Health Sciences Center

🇨🇦

Halifax, Nova Scotia, Canada

Kingston General Hospital

🇨🇦

Kingston, Ontario, Canada

Barrow Neurological Institute

🇺🇸

Phoenix, Arizona, United States

UCSF Fresno Center for Clinical Studies

🇺🇸

Fresno, California, United States

Hoag Memorial Hospital Presbyterian

🇺🇸

Newport Beach, California, United States

Winship Cancer Institute, Emory University

🇺🇸

Atlanta, Georgia, United States

Stanford University Medical Center

🇺🇸

Palo Alto, California, United States

Dent Neurologic Institute

🇺🇸

Amherst, New York, 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

University Hematology Oncology Care, LLC

🇺🇸

Cincinnati, Ohio, United States

Good Samaritan Hospital

🇺🇸

Cincinnati, Ohio, United States

The Ohio State University

🇺🇸

Columbus, Ohio, United States

Virginia Mason Clinic

🇺🇸

Seattle, Washington, United States

CancerCare Manitoba

🇨🇦

Winnipeg, Manitoba, Canada

University of Colorado Cancer Center

🇺🇸

Aurora, Colorado, United States

UC Davis Medical Center, Division of Medical Oncology

🇺🇸

Sacramento, California, United States

Cancer Institute of Orlando

🇺🇸

Orlando, Florida, United States

Hermelin Brain Tumor Center, Henry Ford Hospital

🇺🇸

Detroit, Michigan, United States

Moffitt Cancer Center & Research Institute

🇺🇸

Tampa, Florida, United States

Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

University of Wisconsin

🇺🇸

Madison, Wisconsin, United States

Cross Cancer Institute

🇨🇦

Edmonton, Alberta, Canada

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