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

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.

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