Clinical trial NCT00088166: XERECEPT® (hCRF) for Patients Requiring Dexamethasone to Treat Edema Associated With Brain Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Brain Edema
Brain Tumor
Keywords: peritumoral brain edema
edema
malignant brain tumor
astrocytoma
brain tumor
dexamethasone
Decadron
Lead sponsor: Celtic Pharma Development Services
Sponsor class: INDUSTRY
Collaborators: name: Neurobiological Technologies
First posted: 2004-07-22
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The Proportion of Patients in Each Treatment Group Who Are Responders at Week 2 and Continue to be Responders at Week 5
timeFrame: Prospective
Secondary outcomes:
measure: 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
timeFrame: Prospective
measure: 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
timeFrame: Prospective
measure: Change From Baseline in the 10-Item Neurological Examination Score at Weeks 2, 5, 8 12 and 16 (or Early Discontinuation)
timeFrame: Prospective
measure: Change From Baseline in the Karnofsky Performance Score
timeFrame: Prospective
measure: Change From Baseline in the FACT-Br Quality of Life Results
timeFrame: Prospective
measure: Change From Baseline in Myopathy Assessment Results at Week 12 (or Early Study Drug Discontinuation) and Week 16 (or 4-week Follow-up Visit)
timeFrame: Prospective
measure: Maximum Percent Reduction in Dexamethasone Usage Relative to Baseline Achieved During the Study
timeFrame: Prospective
measure: Number of Patients Who Discontinued Study Drug Prior to the End of Week 5
timeFrame: Prospective
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Fresno
country: United States
facility: UCSF Fresno Center for Clinical Studies
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center, Division of Medical Oncology
state: California
city: San Diego
country: United States
facility: UC San Diego, Thornton Hospital
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Englewood
country: United States
facility: Colorado Neurological Institute
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Orlando
country: United States
facility: Cancer Institute of Orlando
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center & Research Institute
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University, Feinberg School of Medicine
state: Illinois
city: Evanston
country: United States
facility: Evanston Northwestern Healthcare
state: Illinois
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Hermelin Brain Tumor Center, Henry Ford Hospital
state: Michigan
city: Ridgewood
country: United States
facility: Neurology Group of Bergen County
state: New Jersey
city: Amherst
country: United States
facility: Dent Neurologic Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: Cincinnati
country: United States
facility: University Hematology Oncology Care, LLC
state: Ohio
city: Cincinnati
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Portland
country: United States
facility: Oregon Clinic
state: Oregon
city: Seattle
country: United States
facility: Virginia Mason Clinic
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Moncton
country: Canada
facility: The Moncton Hospital
state: New Brunswick
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Center
state: Nova Scotia
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook and Women's College Health
state: Ontario
Study officials:
affiliation: Barrow Neurological Institute
name: William Shapiro, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Recht L, Mechtler LL, Wong ET, O'Connor PC, Rodda BE. Steroid-sparing effect of corticorelin acetate in peritumoral cerebral edema is associated with improvement in steroid-induced myopathy. J Clin Oncol. 2013 Mar 20;31(9):1182-7. doi: 10.1200/JCO.2012.43.9455. Epub 2013 Feb 4.