Clinical trial NCT01381718: Modafinil in Treating Children With Memory and Attention Problems Caused by Cancer Treatment for a Brain Tumor
Official title: A Phase II Placebo-Controlled Trial of Modafinil to Improve Neurocognitive Deficits in Children Treated for a Primary Brain Tumor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Cognitive/Functional Effects
Fatigue
Neurotoxicity
Psychosocial Effects of Cancer and Its Treatment
Keywords: childhood brain tumor
neurotoxicity
fatigue
cognitive/functional effects
psychosocial effects of cancer and its treatment
Lead sponsor: University of South Florida
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2011-06-27
Enrollment: 112
Sex: ALL
Minimum age (years): 6
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Age-Adjusted Scores at Week Six From Baseline in the Attention Task of the CogState Battery
timeFrame: Baseline and 6 weeks
Secondary outcomes:
measure: Number of Reported Adverse Events (AEs)
timeFrame: 30 days post intervention
measure: Change in Working Memory Score at 6 Weeks From Baseline as Assessed on BRIEF
timeFrame: Baseline and 6 weeks
measure: Change in PedsQL Score at 6 Weeks From Baseline
timeFrame: Baseline and 6 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Long Beach
country: United States
facility: Miller Children's Hospital
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital Stanford University
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital - San Diego
state: California
city: Denver
country: United States
facility: Children's Hospital of Colorado; Saint Joseph Hospital
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Wilmington
country: United States
facility: A. I. duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Fort Myers
country: United States
facility: Lee Memorial Health System
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Hollywood
country: United States
facility: Joe DiMaggio Children's Hospital
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Pensacola
country: United States
facility: Nemours Children's Clinic- Pensacola
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Tampa
country: United States
facility: SunCoast CCOP Research Base at the University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children
state: Hawaii
city: Boise
country: United States
facility: St. Luke's Mountain States Tumor Institute
state: Idaho
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children- Indiana University
state: Indiana
city: Louisville
country: United States
facility: Kosair Children's Hospital
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Ann Arbor
country: United States
facility: CS Mott/University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospital and Clinics
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis University / Cardinal Glennon Children's Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis University Cancer Center
state: Missouri
city: Las Vegas
country: United States
facility: Nevada Cancer Research Foundation
state: Nevada
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Saint Peter's University Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Akron
country: United States
facility: Children's Hospital Medical Center of Akron
state: Ohio
city: Dayton
country: United States
facility: Dayton Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Doernbecher Children's Hospital/ Oregoon Health Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Knoxville
country: United States
facility: East Tennessee Children's Hospital
state: Tennessee
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Children's Hospital
state: Tennessee
city: Corpus Christi
country: United States
facility: Driscoll Children's Hospital
state: Texas
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Green Bay
country: United States
facility: St. Vincent Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center
state: Wisconsin
Study officials:
affiliation: University of South Florida
name: Jeffrey P. Krischer, MD, PhD
role: STUDY_CHAIR
affiliation: Boston Children's Hospital
name: Nicole J. Ullrich, MD, PhD
role: STUDY_CHAIR
References: