A Randomized, Double Blind, Placebo-Controlled Study Evaluating the Effect of Nuvigil® (Armodafinil) in Newly Diagnosed Malignant Glioma Patients Experiencing Fatigue Secondary to External Beam Radiation Therapy and Concurrent Temozolomide

Inclusion Criteria:

- Ages 18 years or greater at study entry

- Histologic diagnosis of a supratentorial World Health Organization (WHO) grade 3
anaplastic glioma (including astrocytoma, oligodendroglioma, and mixed
oligoastrocytoma) or WHO grade 4 glioblastoma which requires external beam radiation
therapy (EBRT) and concurrent temozolomide (TMZ)

- Have adequate renal and liver function as evidenced by the following screening lab
values: Creatinine ≤ 1.7mg/dl; Total Bilirubin ≤ 1.5mg/dl; Transaminases ≤ 4 times
above the upper normal limit; Prothrombin time/international normalized ratio
(PT/INR) < 1.4 for patients not on warfarin

- Adequate bone marrow functions as defined by the following lab values: Absolute
neutrophil count (ANC) ≥ 1,500/mm³; Platelets ≥ 100,000 cells/mm³; Hemoglobin ≥
10.0 gm/dL; White blood cell count (WBC) ≥ 3,000/mcL

- Karnofsky Performance Status ≥ 60%

- Recovered from the immediate neurosurgical post-operative period (e.g. for
craniotomy, at least a 2 week period of time to allow for wound healing)

- Agrees to use acceptable birth control method(s). Females using steroidal
contraception (oral, depot, or implantable) must agree to use an alternative or
concomitant method of contraception throughout therapy as well as for one month after
discontinuation of therapy.

- Agrees to avoid alcohol consumption while on therapy

Exclusion Criteria:

- Pre-existing documented traumatic brain injury

- Pre-existing dementing illness due to degenerative, cerebrovascular, or other static
or progressive neurologic process

- Neurological deficit such as hemineglect or homonymous hemianopsia on baseline
neurologic examination that would preclude effective participation in cognitive
testing

- Intracranial space occupying lesion other than malignant glioma or benign
asymptomatic meningioma

- Prior treatment with EBRT or stereotactic radiosurgery (SRS) to the brain

- Prior treatment with Nuvigil® or Provigil® within 4 weeks prior to study entry

- Leptomeningeal disease suggested clinically or by radiographic criteria

- History of left ventricular cardiac hypertrophy

- Ischemic ECG changes, chest pain, arrhythmia, or other clinically significant
manifestations of mitral valve prolapse in association with central nervous system
(CNS) stimulant use within the past 6 months

- Unstable angina or myocardial infarction within the past 6 months

- Premorbid or ongoing psychosis

- Currently receiving Ritalin or Tricyclic Antidepressants. Nuvigil has been
demonstrated to affect the serum levels of Triazolam and Cyclosporine. Patients
taking these medications will be monitored for potential dose adjustments. Other
medications that are metabolized by the cytochrome P450 pathway may be potentially
affected, but have not been demonstrated to do so in clinical testing. Such
medications will be monitored throughout the study for possible dose adjustments.

- Patients who are experiencing significant fatigue secondary to medical or physiologic
causes other than primarily from their malignant gliomas

- Pregnant, breast-feeding, or lack of willingness to use recommended birth control
methods

- Patients with known hypersensitivity to modafinil, armodafinil, or its inactive
ingredients

- Patients unable to understand or comply with all conditions of the protocol