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

RATIONALE: Armodafinil may help relieve fatigue and improve quality of life in patients with cancer receiving radiation therapy to the brain.

PURPOSE: This clinical trial is studying how well armodafinil works 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.

Eligibility Criteria:
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)