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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01032200
Recruitment Status : Completed
First Posted : December 15, 2009
Results First Posted : February 13, 2017
Last Update Posted : September 10, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Brain Tumors Nervous System Tumors Cognition Disorders Fatigue Drug: Armodafinil Other: placebo Phase 2

Detailed Description:



  • 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.


  • 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: A Feasibility Study of Armodafinil for Brain Radiation-Induced Fatigue
Study Start Date : August 2010
Actual Primary Completion Date : November 2013
Actual Study Completion Date : November 2013

Arm Intervention/treatment
Experimental: Arm I - Armodafinil
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.
Drug: Armodafinil
Given orally

Placebo Comparator: Arm II - Placebo
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.
Other: placebo
Given orally

Primary Outcome Measures :
  1. Retention [ Time Frame: 4 weeks post-RT (approximately 3 months post randomization) ]
    Retention is defined as the percentage of participants who complete the 4 week post-RT questionnaires.

  2. Adherence [ Time Frame: 4 weeks post-RT (approximately 3 months post randomization) ]
    Adherence is the percentage of ideal number of pills taken while on study (based on returned diaries)

Secondary Outcome Measures :
  1. Fatigue [ Time Frame: 4 weeks post-RT ]
    Fatigue is measured by the fatigue subscale of the Functional Assessment of Chronic Illness Therapy Questionnaire. It consists of 13 questions each answered on a 0 to 4 scale. The fatigue score is the sum of the responses with some questions reverse scored. The total Score ranges from 0 to 52, with higher scores indicating less fatigue.

  2. Sleepiness [ Time Frame: 4 weeks post-RT ]
    Sleepiness as measured by the Epworth Sleep Scale. It consists of 8 questions that measure daytime sleepiness in which the patient records their likelihood of dozing or sleeping during a number of routine daily activities. ESS scores range from 0 to 24. Higher scores denote greater sleepiness.

  3. HVLT-IR [ Time Frame: 4 weeks post-RT ]
    HVLT-IR is the Hopkins Verbal learning test - immediate recall. Participants are given 12 words to remember. They are then asked to recall those words. This is repeated 3 times. Minimum recalled words 0 maximum 36. The HVLT-IR score is the sum of correctly recalled words across the three trials. Higher scores indicate better recall.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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


  • 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)


  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01032200

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United States, North Carolina
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
Sponsors and Collaborators
Wake Forest University Health Sciences
National Cancer Institute (NCI)
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Principal Investigator: Edward G. Shaw, MD Wake Forest University Health Sciences

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Responsible Party: Wake Forest University Health Sciences Identifier: NCT01032200     History of Changes
Other Study ID Numbers: IRB00012856
U10CA081851 ( U.S. NIH Grant/Contract )
REBACCCWFU97509 ( Other Identifier: NCI )
First Posted: December 15, 2009    Key Record Dates
Results First Posted: February 13, 2017
Last Update Posted: September 10, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Wake Forest University Health Sciences:
cognitive/functional effects
adult giant cell glioblastoma
adult glioblastoma
adult gliosarcoma
adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult mixed glioma
adult diffuse astrocytoma
adult pilocytic astrocytoma
adult pineal gland astrocytoma
adult subependymal giant cell astrocytoma
adult oligodendroglioma
adult anaplastic ependymoma
adult ependymoma
adult myxopapillary ependymoma
adult subependymoma
adult anaplastic meningioma
adult grade I meningioma
adult grade II meningioma
adult grade III meningioma
adult papillary meningioma
adult brain stem glioma
Additional relevant MeSH terms:
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Brain Neoplasms
Nervous System Neoplasms
Cognition Disorders
Signs and Symptoms
Central Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Central Nervous System Stimulants
Physiological Effects of Drugs
Wakefulness-Promoting Agents
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 Enzyme Inducers
Molecular Mechanisms of Pharmacological Action