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

Condition(s) targeted: Brain Edema; Brain Tumor

Intervention: hCRF (Drug); placebo hCRF (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Celtic Pharma Development Services

Official(s) and/or principal investigator(s):
William Shapiro, MD, Principal Investigator, Affiliation: Barrow Neurological Institute

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.

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 design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: The proportion of patients in each treatment group who are Responders at Week 2 and continue at Week 5

Secondary outcome:

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

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

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).

Change from Baseline in the Karnofsky Performance Score at Weeks 2, 5, 8, 12 (or Early Study Drug Discontinuation), and 16 (or 4-week Follow-up visit)

Change from Baseline in the Signal Symptom Score at Weeks 2, 5, 8, 12 (or Early Study Drug Discontinuation), and 16 (or 4-week Follow-up visit)

Change from Baseline in the FACT-Br quality of life results at Weeks 5, 12 (or Early Study Drug Discontinuation), and 16

Change from Baseline in Myopathy assessment results at Week 12 (or Early Study Drug Discontinuation) and Week 16 (or 4-week Follow-up visit)

Maximum percent reduction in dexamethasone usage relative to Baseline achieved during the study

Time to discontinuation of blinded study medication prior to the end of Week 5

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

Cross Cancer Institute, Edmonton, Alberta T6G1ZT, Canada

Barrow Neurological Institute, Phoenix, Arizona 85013, United States

UC San Diego, Thornton Hospital, San Diego, California 92037, United States

UC Davis Medical Center, Division of Medical Oncology, Sacramento, California 95817, United States

Stanford University Medical Center, Palo Alto, California 94305, United States

Hoag Memorial Hospital Presbyterian, Newport Beach, California 92658, United States

UCSF Fresno Center for Clinical Studies, Fresno, California 93702, United States

Colorado Neurological Institute, Englewood, Colorado 80113, United States

University of Colorado Cancer Center, Aurora, Colorado 80045, United States

Cancer Institute of Orlando, Orlando, Florida 32804, United States

Mayo Clinic, Jacksonville, Florida 32224, United States

Moffitt Cancer Center & Research Institute, Tampa, Florida 33612-9497, United States

Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, United States

Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, United States

Evanston Northwestern Healthcare, Evanston, Illinois 60201, United States

CancerCare Manitoba, Winnipeg, Manitoba R3E 0V9, Canada

Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States

Hermelin Brain Tumor Center, Henry Ford Hospital, Detroit, Michigan 48202, United States

The Moncton Hospital, Moncton, New Brunswick E1C 6Z8, Canada

Neurology Group of Bergen County, Ridgewood, New Jersey 07450, United States

Memorial Sloan Kettering Cancer Center, New York, New York 10021, United States

Dent Neurologic Institute, Amherst, New York 14226, United States

Weill Medical College of Cornell University, New York, New York 10021, United States

Queen Elizabeth II Health Sciences Center, Halifax, Nova Scotia B3H 1V7, Canada

The Ohio State University, Columbus, Ohio 43210, United States

University Hematology Oncology Care, LLC, Cincinnati, Ohio 43210, United States

Good Samaritan Hospital, Cincinnati, Ohio 45220, United States

Ottawa Regional Cancer Centre, OTTAWA, Ontario K1H 1C4, Canada

Kingston General Hospital, Kingston, Ontario K7L 5P9, Canada

Sunnybrook and Women's College Health, Toronto, Ontario M4N 3M5, Canada

Oregon Clinic, Portland, Oregon 97210, United States

Virginia Mason Clinic, Seattle, Washington 98111, United States

University of Wisconsin, Madison, Wisconsin 53792, United States

Medical College of Wisconsin, Milwaukee, Wisconsin 53226-3596, United States

Starting date: May 2004
Ending date: March 2008
Last updated: March 7, 2008