Armodafinil in Treating Fatigue Caused By Radiation Therapy in Patients With Primary Brain Tumors

OBJECTIVES:

Primary

- To estimate study accrual, adherence, retention, and participation of patients with
primary brain tumors undergoing partial- or whole-brain radiotherapy who are randomized
to receive armodafinil or placebo.

- To estimate the variability of fatigue, quality of life, and neurocognitive function in
these patients.

Secondary

- To obtain a preliminary estimate of the effect of armodafinil on fatigue as measured by
the fatigue subscale of the FACIT-F and the Brief Fatigue Inventory.

- To estimate the rates of toxicity and adverse events associated with armodafinil.

- To obtain preliminary estimates of the effect of armodafinil on sleepiness as measured
by the Epworth Sleep Scale; overall quality of life and brain-specific quality of life
as measured by the FACT-G with the brain subscale; and cognitive function as measured by
a comprehensive Wake Forest Cognitive Function Battery.

OUTLINE: This is a multicenter study. Patients are stratified according to therapy
(radiotherapy alone vs radiotherapy and chemotherapy) and Karnofsky performance status
(60-80% vs 90-100%). Patients are randomized to 1 of 2 arms.

- Arm I: Patients receive oral armodafinil once daily beginning no later than the fifth
fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of
unacceptable toxicity.

- Arm II: Patients receive oral placebo once daily beginning no later than the fifth
fraction of brain radiotherapy and continuing for 9-11 weeks in the absence of
unacceptable toxicity.

Patients complete questionnaires assessing fatigue, quality of life, and neurocognitive
function at baseline and periodically during study.

Inclusion Criteria

- Histologically confirmed primary brain tumor, including any of the following:

- Glioblastoma multiforme

- Anaplastic astrocytoma

- Anaplastic oligodendroglioma

- Anaplastic mixed oligoastrocytoma

- Low-grade glioma

- Meningioma

- Ependymoma

- Other primary brain tumor histologies

- Planning to undergo external-beam cranial radiotherapy (partial- or whole-brain
radiotherapy) meeting all of the following criteria:

- Total dose ≥ 4,500 cGy

- Total number of fractions ≥ 25 fractions

- Dose per fraction ≥ 150 cGy

PATIENT CHARACTERISTICS:

- Karnofsky performance status 60-100%

- Hemoglobin ≥ 10.0 g/dL (erythropoietin or transfusion allowed for symptomatically
anemic patients with a hemoglobin < 10 g/dL)

- Creatinine ≤ 2 mg/dL

- Total bilirubin ≤ 2 times upper limit of normal (ULN)

- SGOT and SGPT ≤ 3 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Sexually active women of childbearing potential must use a reliable method of birth
control

- It is recommended that patients use non-hormonal contraceptives, in addition to
or in place of hormonal contraceptives, during and for one month following
treatment with armodafinil

- Prior malignancies allowed

Exclusion Criteria:

- No baseline headaches (i.e., headaches occurring in the week before baseline
assessment) of grade 4 severity (defined as severe and disabling headaches, requiring
analgesics, and interfering with and preventing function or activities of daily
living)

- No concurrent uncontrolled illness that may cause fatigue; interfere with drug
absorption, distribution, metabolism, or excretion; or limit compliance with study
requirements including, but not limited to, any of the following:

- Ongoing or active infection

- Chronic renal insufficiency

- Psychiatric illness (psychosis, psychotic disorder, history of suicide attempt,
or actively suicidal)

- Extreme social situations (e.g., transportation issues that would preclude study
compliance)

- Patients with a history of cardiac issues (symptomatic congestive heart failure,
unstable angina pectoris, cardiac arrhythmia) should not use armodafinil as it may
cause chest pain, palpitations, dyspnea, and transient ischemic T-wave changes on ECG

- No history of allergic reaction attributed to modafinil or armodafinil

- No anticipated or planned excessive consumption of coffee, tea, and/or
caffeine-containing beverages averaging > 600 mg of caffeine/day (i.e., approximately
6 cups of coffee/day, 12 cups of hot tea/day, or 12 cans of cola/day)

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior fractionated external-beam cranial radiotherapy

- More than 30 days since prior monoamine oxidate inhibitors or investigational drugs

- More than 2 weeks since prior and no concurrent modafinil (Provigil), donepezil
(Aricept), memantine hydrochloride (Namenda), methylphenidate (Ritalin),
dextroamphetamine-amphetamine (Adderall), ginkgo biloba, or any other cognitive
function-enhancing drugs

- At least 4 weeks since prior and no concurrent interstitial or intracavitary
chemotherapy and/or radiotherapy or stereotactic radiosurgery (i.e., Gamma Knife,
Linac, or Cyberknife)

- No concurrent erythropoietin, transfusion, or iron therapy (unless patient is
symptomatically anemic with hemoglobin < 10 g/dL)

- Concurrent chemotherapy allowed

- Concurrent hormonal therapy for other malignancies allowed

- No concurrent non-hormonal therapy (e.g., Herceptin and other targeted agents),
or cytotoxic chemotherapy

- No concurrent clopidogrel bisulfate (Plavix)