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

Phase 2

Completed

Conditions: Cognition Disorders
Fatigue
Brain Tumors
Nervous System Tumors

Interventions: Other: placebo
Drug: Armodafinil

Registration Number: NCT01032200

Lead Sponsor: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 54

Inclusion Criteria

Not provided

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II - Placebo	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.
Arm I - Armodafinil	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.

Primary Outcome Measures

Name	Time	Method
Retention	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.
Adherence	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

Name	Time	Method
Fatigue	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.
Sleepiness	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.
HVLT-IR	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.