ACCL0922, (SCUSF 0901) A Phase II Placebo-Controlled Trial of Modafinil to Improve Neurocognitive Deficits in Children Treated for a Primary Brain Tumor
Cancer-related neurocognitive dysfunction (CRNCD) is a condition affecting 40-
100% of long-term brain tumor survivors.
Manifestations of CRNCD include impaired working memory, reduced
processing speed, decreased reaction time and decreased attention. There are few
published interventional trials aimed at reversing or preventing CRNCD. Use of
methylphenidate in children includes limitations such as short half-life;
unpredictability of toxicity and efficacy; high rate of dose-limiting events and
relatively poorer tolerance in patients with brain tumors.
Modafinil is a well-tolerated, dopaminergic central nervous system
psychostimulant that can be administered once daily. There is growing evidence
that modafinil may specifically benefit patients with CRNCD. For example, in a
randomized clinical trial of breast cancer survivors, modafinil significantly
improved attention and speed of memory following cancer treatment. In 30 adults
with CNS tumors and CRNCD, modafinil improved cognition, mood and fatigue.
Although modafinil is not currently FDA approved in children under the age of
16, it is frequently used clinically to treat narcolepsy, excessive daytime
sleepiness and ADD in children.
Cancer-related fatigue is well documented in adult oncology literature. However,
it is not as well documented in pediatric oncology. Until recently, reliable and
valid tools to specifically measure fatigue in children were not available. This
study evaluates neurocognitive functioning using a brief computerized battery
(CogState) that targets areas known to be most affected in CRCND. The
Multidimensional Fatigue Scale (MFS) of the Pediatric Quality of Life (PedsQL)
Inventory Measurement Model will be used to evaluate modafinil and #146;s effect on
fatigue, including a component addressing cognitive fatigue.
Age ≥ 6 years and ≤ 17 years 10 months
Diagnosis of a primary brain tumor treated with resection, irradiation or chemotherapy
Off-treatment and progression-free for at least 12 months
Parent/guardian/patient proficient in English
Vision/hearing sufficient for valid test administration and cooperation with
examinations (eyeglasses/hearing aid acceptable)
Reliable parent/guardian willing and able to complete all study requirements at all study visits
Negative pregnancy test in females of childbearing potential (> Tanner stage 2 or documented hormonal state incompatible with pregnancy) – reliable
contraception must be used throughout the study
Able and willing to sign signed informed consent/assent and HIPAA compliant research authorization