Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Human Corticotropin-Releasing Factor in Controlling Symptoms Associated With Brain Swelling in Patients With Malignant Brain Tumors

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Supportive care Active 18 and over Pharmaceutical / Industry NTI-0303 BCM-H-14962, NCT00088166

Objectives

1. Compare the safety and efficacy of synthetic human corticotropin-releasing factor vs placebo to control symptoms of peritumoral edema in patients with malignant brain tumors requiring chronic administration of high-dose dexamethasone.

Entry Criteria

Disease Characteristics:

• Histologically confirmed primary or metastatic malignant brain tumor
  • Documentation and histology (if available) of primary source of cancer for metastatic disease



• Must have 1 or more of the following qualifying steroid-associated side effect(s):
  • Behavioral changes
  • Insomnia
  • Myopathy
  • Thin, fragile skin, purpura and ecchymoses
  • Inhibition of wound healing
  • Acne
  • Rash
  • Increased appetite
  • Weight gain
  • Hyperglycemia (not due to pre-steroid diabetes and requiring treatment)
  • Redistribution of body fat (cushingoid facial features)
  • Peripheral ankle edema



• Peritumoral brain edema confirmed by MRI or comparable diagnostic technology within the past 21 days



• Requirement for dexamethasone to control symptoms of peritumoral edema for at least 30 days
  • Dose stable (8-24 mg/day) for the past 14 days



• No clinical signs or symptoms of cerebral herniation

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• No introduction of any new chemotherapeutic regimen during the first 5 weeks of study treatment
  • Concurrent treatment with chemotherapy that was initiated before study entry allowed

Endocrine therapy

• See Disease Characteristics
• No concurrent systemic steroids for any indication other than peritumoral brain edema
• No concurrent dexamethasone as an antiemetic

Radiotherapy

• No radiotherapy or radiosurgery during the first 5 weeks of study treatment

Surgery

• No surgery during the first 5 weeks of study treatment

Other

• Concurrent gastrointestinal prophylactic treatment allowed
• Concurrent maintenance anticonvulsant therapy allowed
• No concurrent enrollment in any other investigational drug or device study

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 50-100%

Life expectancy

• At least 4 months

Hematopoietic

• Not specified

Hepatic

• Liver function tests < 1.5 times upper limit of normal
• No liver disease

Renal

• No serious renal disease that would preclude study participation

Cardiovascular

• No serious cardiovascular disease that would preclude study participation
• No arterial hemorrhage

Pulmonary

• No serious pulmonary disease that would preclude study participation
• No asthma

Gastrointestinal

• No serious gastrointestinal disease that would preclude study participation
• No active peptic ulcer

Neurological

• No prior or concurrent confounding neurological disorder that would preclude adequate clinical evaluation
• No clinically significant head injury or chronic seizure disorder that would result in functional impairment or preclude clinical evaluations
• No CNS infection

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known hypersensitivity to niacin
• No serious endocrine or metabolic disease that would preclude study participation
• No other condition that would preclude the administration of niacin
• Able to self-administer subcutaneous (SC) injections OR available family member or friend able to administer SC injections

Expected Enrollment

A total of 200 patients (100 per treatment arm) will be accrued for this study within 1-1.5 years.

Outcomes

Response rate at week 2 and continued response rate at week 5 of patients who responded at week 2
Reduction in dexamethasone dose relative to baseline by ≥ 50% at weeks 2 and 5
Overall unchanged or a lowered 10-item neurological examination score relative to baseline at weeks 2 and 5
Performance status changes relative to baseline as measured by Karnofsky Performance Score (KPS) at weeks 2 and 5

Percentage of patients achieving 50% reduction in dexamethasone usage relative to baseline without deterioration of neurological function as measured by a 10-item neurological examination by week 2
Proportion of patients who responded at 2 weeks who continue to respond at 5 and 8 weeks
Compare the baseline results of the 10-item neurological examination score with assessments taken at weeks 2, 5, 8, 12, and 16

Outline

This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to tumor type (primary vs metastatic), open-label dexamethasone dose at baseline (4-16 mg/day vs 17-24 mg/day), and Karnofsky performance status (50-70% vs 80-100%). Patients are randomized to 1 of 2 treatment arms.

All patients receive open-label oral dexamethasone daily at tapering doses on weeks 1-12. After week 12, patients may receive additional dexamethasone (as needed) until week 16.

• Arm I: Patients receive synthetic human corticotropin-releasing factor subcutaneously (SC) twice daily and oral placebo twice daily.



• Arm II: Patients receive placebo SC twice daily and oral niacin twice daily.

In both arms, treatment continues for 12 weeks in the absence of a decrease in the level of consciousness, a worsening of the Signal Neurologic Symptom score for a minimum duration of 2 days, or a requirement for additional dexamethasone.

Patients are followed for 16 weeks and then at 6 and 12 months.

Trial Contact Information

Trial Lead Organizations

Neurobiological Technologies, Incorporated

Lisa Carr, MD, PhD, Protocol chair		Ph: 510-262-1730 Email: carrl@ntii.com

U.S.A.
Arizona
	Phoenix
	Barrow Neurological Institute at St. Joseph's Hospital and Medical Center
		Greta Ludwig	Ph:  602-406-6233 800-227-7691
			Email: gludwig2@chw.edu
California
	La Jolla
	Rebecca and John Moores UCSD Cancer Center
		Clinical Trials Office - Rebecca and John Moores UCSD Cancer Center	Ph:  858-822-5354
			Email: cancercto@ucsd.edu
	Los Angeles
	Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
		Diane Tryclecky, RN	Ph:  310-423-2313
	USC/Norris Comprehensive Cancer Center and Hospital
		Clinical Trials Office - USC/Norris Comprehensive Cancer Center and Hospital	Ph:  323-865-0451
	Sacramento
	University of California Davis Cancer Center
		Clinical Trials Office - University of California Davis Cancer Center	Ph:  916-734-3089
Colorado
	Aurora
	University of Colorado Cancer Center at UC Health Sciences Center
		Clinical Trials Office - University of Colorado Cancer Center	Ph:  720-848-0650
	Englewood
	Colorado Neurological Institute
		Carol Greenwald, MD	Ph:  303-806-7418
			Email: cgreenwald@thecni.org
Florida
	Jacksonville
	Mayo Clinic - Jacksonville
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
	Orlando
	Florida Hospital Cancer Institute
		Clinical Trials Office - Florida Hospital Cancer Institute	Ph:  407-303-5623
	Tampa
	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
		Clinical Trials Office - H. Lee Moffitt Cancer Center and Reseach Institute	Ph:  800-456-7121
			Email: canceranswers@moffitt.org
Georgia
	Atlanta
	Winship Cancer Institute of Emory University
		Ellen McKenzie, RN	Ph:  404-778-5344 888-946-7447
			Email: ellen_mckenzie@emory.org
Illinois
	Chicago
	Robert H. Lurie Comprehensive Cancer Center at Northwestern University
		Clinical Trials Office - Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Ph:  312-695-1301
			Email: cancer@northwestern.edu
Massachusetts
	Boston
	Beth Israel Deaconess Medical Center
		Clinical Trials Office - Beth Israel Deaconess Medical Center	Ph:  617-667-9925
	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
		Joanna Bradshaw	Ph:  617-632-6589 866-790-4500
New Jersey
	Edison
	John F. Kennedy Medical Center
		Deviyani Mehta, MD	Ph:  732-321-7000 ext. 68897
			Email: dmehta@solarishs.org
New York
	Amherst
	DENT Neurologic Institute - Amherst
		Clinical Trials Office - DENT Neurologic Institute - Amherst	Ph:  716-250-2028
	New York
	Memorial Sloan-Kettering Cancer Center
		Bertha Fearon	Ph:  646-227-2064 800-525-2225
			Email: fearonb@mskcc.org
Texas
	Houston
	Dan L. Duncan Cancer Center at Baylor College of Medicine
		Clinical Trials Office - Dan L. Duncan Cancer Center at Baylor College of Medicine	Ph:  713-798-1297
Utah
	Salt Lake City
	Huntsman Cancer Institute at University of Utah
		Clinical Trials Office - Huntsman Cancer Institute at University of Utah	Ph:  801-581-4477
			Email: clinical.trials@hci.utah.edu
Washington
	Seattle
	Floyd and Delores Jones Cancer Institute at Virginia Mason Medical Center
		Lynne Taylor, MD	Ph:  206-341-0420
			Email: ltaylor@u.washington.edu
Canada
Alberta
	Edmonton
	Cross Cancer Institute at University of Alberta
		Shelley Sass	Ph:  780-432-8595
			Email: shelleys@cancerboard.ab.ca
Manitoba
	Winnipeg
	CancerCare Manitoba
		Barb Ameter	Ph:  204-787-4105 ext. 2140
			Email: barb.ammeter@cancercare.mb.ca
Nova Scotia
	Halifax
	Nova Scotia Cancer Centre
		Lisa Cicchelli, RN	Ph:  902-473-3130
			Email: lisa.cicchelli@cdha.nshealth.ca
Ontario
	Kingston
	Cancer Centre of Southeastern Ontario at Kingston General Hospital
		Ivan Agatiello	Ph:  613-544-2631 ext. 6736
			Email: ivan.agatiello@krcc.on.ca
	Ottawa
	Ottawa Hospital Regional Cancer Centre - General Campus
		Nancy Page	Ph:  613-737-7700 ext. 6866 888-627-5346
			Email: napage@ohri.ca
	Toronto
	Edmond Odette Cancer Centre at Sunnybrook
		Rosemary Cashman	Ph:  416-480-6100 ext. 7364
			Email: rosemaryc@swchsc.on.ca
Quebec
	Montreal
	Montreal Neurological Institute and Hospital
		Richard Leblanc, MD	Ph:  514-398-1939
Saskatchewan
	Regina
	Regina General Hospital
		Marilyn Reid	Ph:  306-525-3586

Registry Information
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 Tumors Who Require Chronic Administration of High-Dose Dexamethasone
Registered in ClinicalTrials.gov		NCT00088166
Date Submitted to PDQ		2004-07-22
Information Last Verified		2007-01-11

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