Modafinil in Treating Children With Memory and Attention Problems Caused by Cancer Treatment for a Brain Tumor

Fatigue Clinical Trial

Official title:

A Phase II Placebo-Controlled Trial of Modafinil to Improve Neurocognitive Deficits in Children Treated for a Primary Brain Tumor

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01381718
• Other study ID #: SCUSF 0901
• Secondary ID: SCUSF-0901ACCL09
• Status: Completed
• Phase: Phase 2
• Start date: August 2011
• Est. completion date: August 2016

Study information

• Verified date: September 2018
• Source: University of South Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Modafinil may help improve memory, attention, and fatigue caused by cancer treatment.

PURPOSE: This phase II randomized trial studies how well modafinil works in treating children with memory and attention problems caused by cancer treatment for a brain tumor.

Description:

OBJECTIVES:

Primary

• Determine whether a 6-week drug trial of modafinil, compared to placebo, is associated with improvement in neurocognitive function as defined by direct assessment of attention in children with cognitive impairment after treatment for a primary brain tumor.

Secondary

• Determine whether modafinil, compared to placebo, is associated with improved executive function, as assessed using the BRIEF executive function and hippocampal learning and executive function tasks from the CogState battery. Determine whether modafinil, compared to placebo, is associated with improved attention, as assessed by the Conners' (3rd Edition) 3 Parent Rating Scale (CPRS-3) - Short Form.

• Determine whether modafinil, compared to placebo, is associated with reduced fatigue as assessed using the PedsQL Multidimensional Fatigue Scale.

• Evaluate the safety of modafinil in this population.

OUTLINE: This is a multicenter study. Participants are randomized to 1 of 2 treatment arms.

• Arm I: Participants receive modafinil orally (PO) once daily (QD) on days 1-42.

• Arm II: Participants receive placebo PO QD on days 1-42. Participants complete a semi-automated, computerized cognitive-testing system (CogState) designed to assess psychomotor, attention/vigilance, memory, and other components of executive function by presenting different tasks, each with its own set of rules, at baseline and after completion of study therapy. Participants also complete the PedsQL Multidimensional Fatigue Scale (Peds QL-MFS).

Parents or legal guardians complete the PedsQL-MFS, the Conners Parent Reported Scale (CPR-3), and the Behavior Rating Inventory of Executive Function (BRIEF) at baseline and after completion of study therapy.

Clinical and/or research staff administer the Systematic Assessment for Treatment Emergency Events (SAFTEE), a semi-structured interview designed to elicit adverse events, at baseline and periodically during study.

After completion of study therapy, participants are followed up for 30 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 19 Years

Eligibility

INCLUSION CRITERIA:

• Age = 6 years and = 18 years 10 months at the time of study entry (so that participants will be < 19 at the 6 week evaluation, which is the upper age limit for which the included instruments are valid).

• Diagnosis of a primary brain tumor treated with at least one of the following:

1. neurosurgical resection of the brain tumor;

2. cranial irradiation; or

3. any chemotherapy to treat the brain tumor.

• Off-treatment and progression-free for at least 12 months and = 14 years. Treatment cessation is defined as the final dose of chemotherapy, the last dose (fraction) of radiation or date of surgery, whichever occurred last.

• Parent/Legal Guardian and child able to read English or Spanish.

• Vision and hearing (eyeglasses and/or hearing aid permissible) sufficient for valid test administration and cooperation with examinations.

• Availability of a reliable parent or legal guardian who is willing and able to complete all of the outcome measures and fulfill the requirements of the study, including administration of medications and accompanying the participant to all study visits.

• Females of childbearing potential must have a negative pregnancy test result and must agree to use a medically acceptable method of contraception throughout the entire study period and for 30 days after the last dose of study drug.

• Childbearing potential is defined as girls who are >Tanner stage 2, except for those who have documented pan pituitary insufficiency or other hormonal state incompatible with pregnancy.

• Urine pregnancy tests are acceptable.

EXCLUSION CRITERIA:

• Off treatment > 14 years

• Inability to perform the testing procedure (for example, because of aphasia, motor deficits affecting the dominant hand, or IQ < 70)

• Known cardiac disorders including arrhythmias, hypertension requiring treatment or structural heart disease

• Diagnosis of narcolepsy, sick sinus syndrome, arrhythmia or prolonged QTc

• History of stroke or head injury associated with loss of consciousness within 12 months of registration

• History of grade 2 depression or anxiety or treatment with antidepressants, antipsychotics or MAO inhibitors within 30 days of registration

• Concurrent treatment with any medications or substances that are potent inhibitors or inducers of CYP3A4, hepatic enzyme inducing antiepileptic drugs (EIAEDs),or other drugs known to affect the metabolism of modafinil. Examples include but are not limited to itraconazole, ketoconazole, doxycycline, rifampin, St. John's wort, phenytoin, phenobarbital, diazepam, tricyclic antidepressants.

• If patients were previously taking, EIAEDs, they must be off for > 2 weeks prior to study enrollment.

• Treatment with other stimulant medications within 14 days of registration; however, a diagnosis of ADHD does NOT exclude a child from participation

• Participants with known hypersensitivity to modafinil, armodafinil or any of its components

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Brain Neoplasms
• Central Nervous System Neoplasms
• Cognitive/Functional Effects
• Fatigue
• Nervous System Neoplasms
• Neurotoxicity
• Neurotoxicity Syndromes
• Psychosocial Effects of Cancer and Its Treatment

Intervention

Drug:
• modafinil
Given PO

Other:
• placebo
Given PO

Locations

Country	Name	City	State
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	University of New Mexico	Albuquerque	New Mexico
United States	CS Mott/University of Michigan	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	St. Luke's Mountain States Tumor Institute	Boise	Idaho
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	University of Virginia	Charlottesville	Virginia
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Dayton Children's Hospital	Dayton	Ohio
United States	Children's Hospital of Colorado; Saint Joseph Hospital	Denver	Colorado
United States	Wayne State University	Detroit	Michigan
United States	Lee Memorial Health System	Fort Myers	Florida
United States	University of Florida	Gainesville	Florida
United States	St. Vincent Hospital	Green Bay	Wisconsin
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Riley Hospital for Children- Indiana University	Indianapolis	Indiana
United States	University of Mississippi	Jackson	Mississippi
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	Children's Mercy Hospital and Clinics	Kansas City	Missouri
United States	East Tennessee Children's Hospital	Knoxville	Tennessee
United States	Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Miller Children's Hospital	Long Beach	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	Children's Hospitals and Clinics of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt Children's Hospital	Nashville	Tennessee
United States	Saint Peter's University Hospital	New Brunswick	New Jersey
United States	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York
United States	New York University Langone Medical Center	New York	New York
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nemours Children's Hospital	Orlando	Florida
United States	Lucile Packard Children's Hospital Stanford University	Palo Alto	California
United States	Nemours Children's Clinic- Pensacola	Pensacola	Florida
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Doernbecher Children's Hospital/ Oregoon Health Science University	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	Saint Louis University / Cardinal Glennon Children's Medical Center	Saint Louis	Missouri
United States	Saint Louis University Cancer Center	Saint Louis	Missouri
United States	All Children's Hospital	Saint Petersburg	Florida
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Rady Children's Hospital - San Diego	San Diego	California
United States	SUNY Upstate Medical University	Syracuse	New York
United States	SunCoast CCOP Research Base at the University of South Florida	Tampa	Florida
United States	Tampa General Hospital	Tampa	Florida
United States	Children's National Medical Center	Washington	District of Columbia
United States	A. I. duPont Hospital for Children	Wilmington	Delaware
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of South Florida	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Age-Adjusted Scores at Week Six From Baseline in the Attention Task of the CogState Battery	CogState Battery. CogState is a semi-automated, computerized cognitive testing system that was developed as a rapid and accurate test of cognitive function specifically for repeated assessment that is sensitive to the effects of medication in children over the age of 5 years and in adults from different language, cultural and socio-economic backgrounds. The CogState tasks to assess processing speed, visual attention, working memory and executive function were used. The CogState battery was administered in the following order: Detection Task, Identification Task, One Card Learning Task, One Back Task, and lastly, the Modified Groton Maze Learning Task. It was administered at baseline and 6 weeks. A positive change from baseline is an improvement. There is not a minimum or maximum since the value is reported as a z-score, but with the mean = 0 and the SD = 1, the range should be between -3 and 3.	Baseline and 6 weeks
Secondary	Number of Reported Adverse Events (AEs)	AEs gathered using SAFTEE (Systematic Assessment for Treatment Emergent Effects) and participant report on daily log.	30 days post intervention
Secondary	Change in Working Memory Score at 6 Weeks From Baseline as Assessed on BRIEF	Behavior Rating Inventory of Executive Function (BRIEF). The BRIEF is a behavior rating scale designed to assess executive functions in the home and school environments. The measure was selected to provide parent-reported outcomes of problems related to attention, memory and executive function that occur in everyday life. The instrument was utilized to measure the change in working memory, according to the parent's perspective only, from baseline to 6 weeks. Scores are linear transformations of raw scores into T scores (mean = 50, SD = 10); higher scores indicate greater difficulties. The baseline score was subtracted from the 6 week score. Positive change from baseline is an improvement. The total scale ranges from 0 to 172. A T score >60 on the BRIEF working memory subscale indicates cognitive impairment.	Baseline and 6 weeks
Secondary	Change in PedsQL Score at 6 Weeks From Baseline	PedsQL is Pediatric Quality of Life Inventory Multi-dimensional Fatigue Scale. This scale is designed as a generic symptom-specific instrument to measure fatigue. Higher scores indicate fewer symptoms of fatigue. It was administered at baseline and 6 weeks. The score is the sum of the answers. The baseline score was subtracted from the 6 week score. A positive change indicates worsening. The scale total score range is from 0-72 for both the parent and patient reported instruments.	Baseline and 6 weeks