Clinical trial NCT01032200: Armodafinil in Treating Fatigue Caused By Radiation Therapy in Patients With Primary Brain Tumors
Official title: A Feasibility Study of Armodafinil for Brain Radiation-Induced Fatigue
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain Tumors
Nervous System Tumors
Cognition Disorders
Fatigue
Keywords: fatigue
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
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-12-15
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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)

Primary outcomes:
measure: Retention
timeFrame: 4 weeks post-RT (approximately 3 months post randomization)
measure: Adherence
timeFrame: 4 weeks post-RT (approximately 3 months post randomization)
Secondary outcomes:
measure: Fatigue
timeFrame: 4 weeks post-RT
measure: Sleepiness
timeFrame: 4 weeks post-RT
measure: HVLT-IR
timeFrame: 4 weeks post-RT
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Edward G. Shaw, MD
role: PRINCIPAL_INVESTIGATOR
References: